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A
Hussein, R. M., S. A. Abdelazim, A. M. H. Elgoly, and M. R. Rizk, "Alterations in Antioxidant Defense System and Oxidative Damage in Experimental Hepatorenal Toxicity Induced by Isoniazid and Rifampicin in Rats: Effect of N-Acetyl Cysteine and White Tea Extract ", International Journal of Science and Research, vol. 6, issue 6, pp. 70-83, 2015.
Abdelazeim, S. A., N. I. Shehata, Hanan Farouk Aly, and S. G. E. Shams, "Amelioration of oxidative stress-mediated apoptosis in copper oxide nanoparticles-induced liver injury in rats by potent antioxidants ", SCIENTIFIC REPORTS, vol. (2020)10:10812, pp. 14, 2020.
Azim, S. A. A., H. A. Darwish, M. Z. Rizk, S. A. Ali, and M. O. Kadry, "Amelioration of titanium dioxide nanoparticles-induced liver injury in mice: possible role of some antioxidants.", Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie, vol. 67, issue 4, pp. 305-14, 2015 Apr. Abstract

This study investigates the efficacy of idebenone, carnosine and vitamin E in ameliorating some of the biochemical indices induced in the liver of titanium dioxide nanoparticles (TiO2 NPs) intoxicated mice. Nano-anatase TiO2 (21 nm) was administered (150 mg/kg/day) for 2 weeks followed by the aforementioned antioxidants either alone or in combination for 1 month. TiO2 NPs significantly increased serum liver function enzyme activities, liver coefficient and malondialdehyde levels in hepatic tissue. They also suppressed hepatic glutathione level and triggered an inflammatory response via the activation of macrophages and the enhancement of tumor necrosis factor-α and interleukin-6 levels. Moreover, the mRNA expression of nuclear factor-erythroid-2-related factor 2, nuclear factor kappa B and Bax was up-regulated whereas that of Bcl-2 was down-regulated following TiO2 NPs. Additionally, these NPs effectively activated caspase-3 and caused liver DNA damage. Oral administration of idebenone (200mg/kg), carnosine (200mg/kg) and vitamin E (100mg/kg) alleviated the hazards of TiO2 NPs with the combination regimen showing a relatively higher effect. The histopathological examination reinforced these findings. In conclusion, oxidative stress could be regarded as a key player in TiO2 NPs-induced liver injury. The study also highlights the anti-inflammatory and the anti-apoptotic potentials of these antioxidants against the detrimental effects of TiO2 NPs.

Elsayed, O. M., S. A. Abdelazim, H. A. Darwish, O. G. Shaker, and M. A. Senousy, "Association of LncRNA‑PAX8‑AS1 and LAIR‑2 polymorphisms along with their expression with clinical and subclinical hypothyroidism", Scientific Reports, vol. 13, issue 6, pp. 1-13, 2023. association_of_lncrna-pax8-asl.pdf
C
Camacho, F. J., A. Isunza, and B. Coutino, "Comparison of tendo-Achilles lengthening alone and combined with neurectomy of the gastrocnemius muscle in the treatment of equinus deformity of the foot associated with clonus in children with cerebral palsy.", Orthopedics, vol. 19, issue 4, pp. 319-22, 1996. Abstract

In a prospective study of 12 children with spastic cerebral palsy and equinus deformity (21 extremities) complicated by clonus, the results of two surgical techniques were compared. Six children had tendo-Achilles lengthening (TAL) alone and six had TAL combined with neurectomy of the gastrocnemius muscle. The equinus deformity was corrected in all children, but of those with neurectomy clonus subsided in 50%, compared to only 27% in those with TAL alone.

Motawi, T. K., S. A. Abdelazim, H. A. Darwish, E. M. Elbaz, and S. A. Shouman, "Could Caffeic Acid Phenethyl Ester Expand the Antitumor Effect of Tamoxifen in Breast Carcinoma?", Nutrition and cancer, pp. 1-11, 2016 Mar 23. Abstract

Despite tamoxifen (TAM) is beneficial in treating a significant proportion of patients with breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis, with a plethora of important biological actions including anticancer activity. This study aimed to explore the cytotoxicity, the type of drugs interaction as well as the apoptotic and autophagic pathways of the combined treatment of TAM and CAPE in MCF-7 cells. Their antitumor activity and effect on survival of mice bearing Ehrlich tumor were also analyzed. The results showed synergistic cytotoxic effects, manifested by significant activation of apoptotic machinery, along with downregulation of protein levels of Bcl-2 and beclin-1, upon using the combination regimen. However, the ratio between microtubule-associated protein light chain 3-II and -I was not altered. Moreover, a decrease in vascular endothelial growth factor level was detected. Similarly, TAM + CAPE increased the life span of tumor-bearing animals and caused a marked regression in their tumor size and weight compared with those treated with either TAM or CAPE alone. In conclusion, CAPE relatively improved the anticancer activity of TAM in both in vitro and in vivo models via its apoptotic and angiostatic potentials.

D
Abdelazim, S. A., O. G. Shaker, O. Ali, M. El-Tawil, and M. A. Senousy, "Differential expression of serum miR-486 and miR-25 in ulcerative colitis and Crohn's disease: Correlations with disease activity, extent, and location.", Pathology, research and practice, vol. 252, pp. 154910, 2023. Abstract

Novel reliable biomarkers of inflammatory bowel disease (IBD) are clinically imperative due to potential limitations of endoscopic techniques. MicroRNAs (miRNAs) have emerged as non-invasive biomarkers of IBD; however, the full disease-specific miRNAs signature for IBD subtypes remains elusive. We evaluated the diagnostic role of circulating miR-486 and miR-25 in IBD patients and their potential ability to discriminate IBD subtypes; ulcerative colitis (UC) and Crohn's disease (CD). Sixty UC patients, 60 CD patients, and 60 healthy controls were recruited. Serum miRNA expression was determined using RT-qPCR. Bioinformatics was employed for target gene and protein-protein interaction (PPI) network analyses. Serum miR-486 was upregulated in CD patients, but didn't change in UC patients compared to controls. Conversely, serum miR-25 was decreased in both CD and UC patients compared to controls. Only miR-486 was differentially expressed between UC and CD patients. Receiver-operating characteristic analysis revealed that serum miR-486 was superior in CD diagnosis (AUC=0.945) and significantly distinguished CD and UC patients, whereas miR-25 showed discriminative potential for both UC and CD from controls. In the multivariate logistic analysis only miR-486 was associated with the risk of CD diagnosis. Serum miR-486 was correlated with CD activity index and location of disease in CD patients, whereas miR-25 was correlated with the type/extent of UC. PPI network analysis revealed common target genes and signaling pathways for both miRNAs. Conclusively, serum miR-486 and miR-25 might serve as new biomarkers of IBD, with serum miR-486 could be employed in risk stratification of IBD subtypes and has the ground for clinical utility in CD diagnosis, whereas miR-25 has potential for UC and CD diagnosis.

G
L., E. M., E. - A. S. A. A., M. A. A., and H. H. A., "Glutathione S-transferase Pi-1 gene methylation in early detection of prostate cancer in Egyptian patients", EDIZIONI MINERVA MEDICA, vol. 22, issue 2, pp. 47-52, 2010.
M
Ali, O., H. A. Darwish, K. M. Eldeib, and S. A. A. Azim, "miR-26a Potentially Contributes to the Regulation of Fatty Acid and Sterol Metabolism In Vitro Human HepG2 Cell Model of Nonalcoholic Fatty Liver Disease", Oxidative Medicine and Cellular Longevity, vol. 2018, pp. 1-11, 2018. Abstract

Nonalcoholic fatty liver disease (NAFLD) is a metabolic-related disorder ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma (HCC). This study aimed at assessing the regulatory and protective role of miR-26a on lipid metabolism and progression of NAFLD in human HepG2 cells loaded with free fatty acids (FFA). Lentivirus expressing miR-26a or negative control miR was used to transduce HepG2 cells and to establish stable cell lines. Gain or loss of function using an miR-26a inhibitor was used to compare triglyceride content (TG), total cholesterol level (CL), total antioxidant capacity (TAC), malondialdehyde (MDA) and the level of apoptosis. In addition, quantitative reverse transcription polymerase chain reaction (qPCR) was used to assess the mRNA levels of lipogenesis, TG synthesis, storage genes, inflammatory and fibrogenic markers, and autophagic besides endoplasmic reticulum (ER) stress markers after gaining or losing the function of miR-26a. miR-26a levels decreased in response to FFA in human HepG2 cells. After the establishment of a stable cell line, the upregulation of miR-26a resulted in the downregulation of TG, CL, and MDA levels, through regulating mRNA levels of genes involved in lipid homeostasis, ER stress marker, inflammatory and fibrogenic markers. Nevertheless, there was a marked increment in the mRNA expression of autophagic marker genes. Moreover, miR-26a overexpression protects the cells from apoptosis, whereas inhibition of miR-26a, using an anti-miR-26a oligonucleotide, decreased the expression of miR-26a which potentially contributes to altered lipid metabolism in HepG2 cells loaded with FFA. In conclusion, these findings suggested that miR-26a has a crucial role in regulating fatty acid and cholesterol homeostasis in HepG2 cells, along with the offered protection against the progression of NAFLD in vitro. Hence, miRNAs could receive growing attention as useful noninvasive diagnostic markers to follow the progression of NAFLD and to identify novel therapeutic targets.

Motawi, T. K., S. A. Abdelazim, H. A. Darwish, E. M. Elbaz, and S. A. Shouman, "Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF-7 Breast Cancer Cells.", Oxidative medicine and cellular longevity, vol. 2016, pp. 3017108, 2016. Abstract

Although Tamoxifen (TAM) is one of the most widely used drugs in managing breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF-7 cells. MCF-7 cells were treated with different concentrations of TAM and/or CAPE for 48 h. This novel combination exerted synergistic cytotoxic effects against MCF-7 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with downregulation of Bcl-2 and Beclin 1 expression levels. However, the mammalian microtubule-associated protein light chain LC 3-II level was unchanged. Vascular endothelial growth factor level was also decreased, whereas levels of glutathione and nitric oxide were increased. In conclusion, CAPE augmented TAM cytotoxicity via multiple mechanisms, providing a novel therapeutic approach for breast cancer treatment that can overcome resistance and lower toxicity. This effect provides a rationale for further investigation of this combination.

P
Sabri, A., M. Omran, S. Abdel Azim, R. Abdelfatah, and S. Shouman, "PB1919 EFFECT OF OCT1 GENE POLYMORPHISM ON RESPONSE TO IMATINIB MESYLATE IN CML PATIENTS", HemaSphere, vol. 3, issue S1, pp. 873, 2019. Abstract

Background:
Imatinib mesylate (IM) has been shown to be highly efficacious in the treatment of Chronic Myeloid Leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes. There is a considerable variability in the level of molecular responses achieved with IM therapy. These differences could result from variable drug level which may be due to genetic factors.

The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter responsible for active uptake of IM into CML cells.

Aims:
We hypothesized that the SNPs of this gene could predict the outcomes of IM therapy in CML patients.

Methods:
Fifty patients with CML at chronic phase were studied. All patients were monitored at outpatient clinic of the National Cancer Institute, Cairo University, Egypt. The study was approved by the NCI Ethical Committee for Clinical Research. Written Informed consent was obtained. The polymorphism of SLC22A1 gene was studied using PCR-RFLP technique. Imatinib mesylate level was determined using HPLC-massspectroscopy.

Results:
The mean IM trough plasma level in patients who achieved unfavorable response (n = 25) was 1019 ± 638 ng/mL, and in patients who achieved favorable response (n = 25) 1353 ± 611 ng/mL (p = 0.04).

In regard to SLC22A1 rs(628031) gene, heterogeneous & variant allele (GA&AA) was significantly correlated to unfavorable response while wild allele GG is linked to favorable response(p = 0.0006).

No significant correlation was detected between SLC22A1 gene polymorphism and drug level (p = 0.08).

Abdelazim, S. A., H. A. Darwish, S. A. Ali, M. Z. Rizk, and M. O. Kadry, "Potential antifibrotic and angiostatic impact of idebenone, carnosine and vitamin E in nano-sized titanium dioxide-induced liver injury.", Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, vol. 35, issue 6, pp. 2402-11, 2015. Abstract

BACKGROUND/AIM: The present study investigated the in vitro and in vivo effects of individual and combined doses of idebenone, carnosine and vitamin E on ameliorating some of the biochemical indices of nano-sized titanium dioxide (n-TiO2) in mice liver.

METHODS: The in vitro cytotoxic effect of nano-sized anatase TiO2 (21 nm) on hepatic cell lines (HepG 2) was investigated. Additionally, n-TiO2 was orally administered (150 mg/kg/day) for 2 weeks, followed by a daily intragastric gavage of the aforementioned antioxidants for 1 month.

RESULTS: n-TiO2 induced significant cytotoxicity in hepatic cell lines and elevated the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic total antioxidant capacity (TAC) and nitrite/nitrate (NOx) levels. Meanwhile, glutathione-S-transferase (GST) activity was significantly reduced. Moreover, RT-PCR and western blot analysis showed that n-TiO2 significantly altered the mRNA and protein expressions of transforming growth factor-beta (TGF-β1) and Smad-2, as well as vascular endothelium growth factor (VEGF). Histopathological examination of hepatic tissue reinforced these results.

CONCLUSION: Idebenone, carnosine and vitamin E ameliorated the deviated parameters with the combination regimen demonstrating the most pronounced effect. Oxidative stress, liver fibrosis and angiogenesis may be implicated in n-TiO2-induced liver toxicity.

El-Azim, S. A. A., S. F. Hassan, K. E. M. Deib, and M. M. A. Barakat, "PROTECTIVE EFFECT OF DIETARY GINGER EXTRACT ALONE OR IN COMBINATION WITH ROSIGLITAZONE AND GLIMEPIRIDE ON HEPATOTOXICITY AND OXIDATIVE STRESS IN STREPTOZOTOCIN-INDUCED DIABETES IN RATS", International Journal of Advanced Research, vol. 1, issue 10, 2013. Abstract

The objective of this study was undertaken to evaluate the protective effect
of Ginger extract either alone or in combination with Rosiglitazone and
Glimepiride on serum Glucose, Triglycerides, Cholesterol ,AST, ALT, γ-GT,
as well as liver Malondialdehyde, Catalase (CAT), Superoxide Dismutase
(SOD), reduced Glutathione (GSH) and lysosomal enzymes ;Acid
phospahtase (ACP), β-D-galactosidase (β-GAL) and N-acetyl-β-Dglucosaminidase

(β-NAG), in streptozotocin-induced diabetic rats. The
animals were divided into seven groups: control normal animals (CN),
control untreated diabetic animals (CD) in which experimental
hyperglycemia were induced by single intraperitoneal injection of
streptozotocin (40mg/kg body mass). The other 5 diabetic groups were
treated orally for 30 days with Rosiglitazone (D/Rosi) (0.8 mg/kg b.w),
Glimepiride (D/Glim) (0.8 mg/kg of b.w), Ginger extract (D/G)(500 mg/kg
of body mass), combination of Glimepiride and Ginger extract (D/Glim+G)
and combination of Rosiglitazone and Ginger (D/Rosi+G) starting 24 hours
after streptozotocin injection. The antioxidant effect of the Ginger extract
was compared with Rosiglitazone and Glimepiride, well-known
hypoglycaemic drugs. The diabetic rats exhibited lowered hepatic GSH
content and CAT, SOD activities associated with elevated levels of hepatic
MDA, liver functions enzymes and lysosomal enzymes as compared with
normal rats. In contrast ginger treatment exerts a therapeutic protective effect
in diabetes by decreasing oxidative stress, liver functions enzymes,
lysosomal enzymes and hepatic damage. Ginger extracts showed an
encouraging hypoglycemic, hypolipaemic, as well as antioxidant properties

and could be considered as a valuable candidate in the reversal of the
complication of diabetes.

S
Sabri, A., M. M. Omran, A. S. Azim, R. Abdel Fattah, R. A. S. H. A. M. A. H. M. O. U. D. ALLAM, and S. A. Shouman, "A Study to Explore the Role of IDH1 (R132) Mutation on Imatinib Toxicity and Effect of ABCG2/OCT1 Expression on N-Desmethyl Imatinib Plasma Level in Egyptian Chronic Myeloid Leukemia Patients.", Drug research, vol. 73, issue 3, pp. 146-155, 2023. Abstract

Imatinib mesylate (IM) is the gold standard for treatment of Chronic Myeloid Leukemia (CML). This study aimed to gain more knowledge of the altered PK, pharmacogenetic factors, and gene expression leading to variable IM levels. Fifty patients with chronic phase-CML were enrolled in this study and divided as 25 responders and 25 non-responders (patients are directly recruited after response assessment). HPLC/MS/MS was used to determine trough and peak concentration of imatinib and N-desmethyl imatinib in the blood. PCR-RFLP technique was used to detect IDH1 gene mutation (R132). The median value of IM trough level was significantly higher, the P/T ratio was significantly lower and the α-1-acid glycoprotein (AGP) was significantly higher among responders compared to non-responders (P=0.007, 0.009 and 0.048, respectively). Higher N-desmethyl imatinib peak plasma concentration was observed with low mRNA expression of ABCG2 and OCT1 (P=0.01 and 0.037, respectively). IDH1 R132 gene mutation was associated with a significant increase in toxicities (P=0.028). In conclusion, IM trough level, P/T ratio and AGP was significantly higher in responders. In addition, ABCG2 and OCT1 gene expression may affect the interindividual PK variation. Although a prospective study with a larger patient population is necessary to validate these findings. IDH1 mutation is a predictor of increased toxicity with IM treatment.

T
Azim, S. A. A., R. M. Hussein, A. A. Badr, and M. R. Rizk, "Therapeutic Effects of Bone Marrow-Derived Mesenchymal Stem Cells Against Isoniazid and RifampicinInduced Hepatorenal Toxicity in Rats ", Life Science Journal , vol. 11, issue 12, pp. 1036-1046, 2014.
U
Abdelazim, S. A., O. G. Shaker, Y. A. H. Aly, and M. A. Senousy, "Uncovering serum placental-related non-coding RNAs as possible biomarkers of preeclampsia risk, onset and severity revealed MALAT-1, miR-363 and miR-17.", Scientific reports, vol. 12, issue 1, pp. 1249, 2022. Abstract

New predictors that could boost early detection of preeclampsia (PE) and prognosticate its severity are urgently needed. We examined serum miR-17, miR-363, MALAT-1 and HOTAIR as potential biomarkers of PE risk, onset and severity. This prospective study included 160 pregnant females; 82 PE cases and 78 healthy pregnancies. Serum samples were collected between 20 to 40 weeks of gestation. Early-onset PE was defined as developing clinical manifestations at ≤ 34 gestational weeks. Severe PE was defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg and proteinuria (≥ 2 g/24 h or ≥ 2+ dipstick). Selection of PE-related non-coding RNAs and functional target gene analysis were conducted using bioinformatics analysis. Expression profiles were assessed by RT-qPCR. Serum miR-363 and MALAT-1 were downregulated, meanwhile miR-17 was upregulated, and HOTAIR was not significantly altered in PE compared with healthy pregnancies. miR-17 was elevated while miR-363 and MALAT-1 were reduced in severe versus mild PE. miR-363 was lower in early-onset versus late-onset PE. MALAT-1, miR-17 and miR-363 showed diagnostic potential and discriminated severe PE, whereas miR-363 distinguished early-onset PE in the receiver-operating-characteristic analysis. miR-363 and MALAT-1 were significantly associated with early and severe PE, respectively in multivariate logistic analysis. In PE, miR-17 and MALAT-1 were significantly correlated with gestational age (r = - 0.328 and r = 0.322, respectively) and albuminuria (r = 0.312, and r = - 0.35, respectively). We constructed the MALAT-1, miR-363, and miR-17-related protein-protein interaction networks linked to PE. Serum miR-17, miR-363 and MALAT-1 could have utility as new biomarkers of PE diagnosis. miR-363 may be associated with early-onset PE and MALAT-1 downregulation correlates with PE severity.

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