Publications by authors named "Iman Talaat"

32 Publications

Passive smoking induces nasal biofilms in children.

Int J Pediatr Otorhinolaryngol 2021 Jul 7;146:110755. Epub 2021 May 7.

Clinical Sciences Department, University of Sharjah, United Arab Emirates.

Objectives: Passive exposure of children to cigarette smoke has been implicated in several recalcitrant respiratory childhood disorders. However, to our knowledge, no information is available regarding the connection between passive exposure to tobacco smoke and the formation of nasal biofilms in children. The present study was therefore geared at investigating the hypothesis that exposure of children to household passive smoking may induce the formation of nasal biofilms.

Methods: The study included 20 children between the ages of 6 and 12 years with a positive history of prolonged exposure to household passive smoke, and who required inferior turbinate reduction together with other procedures. Another 20 children who required similar surgeries but with negative history of exposure to household smoking formed the control group. None of children, in the study and control groups, had evidence of adenoids or infective rhinosinusitis. At the time of surgery, a tiny biopsy was taken from the lower border of the inferior turbinate. The specimens were processed for scanning and transmission electron microscopy.

Results: The nasal mucosa of 11 out of 20 children with positive history of exposure to passive smoking showed biofilm formation. Ten of these biofilms grew S. aureus. On the other hand, only one child in the control group showed nasal biofilm. Longer exposure to tobacco smoke and higher urinary cotinine levels were associated with more frequent biofilm formation. Likewise, children of heavy smokers developed biofilms more frequently than other children. On the other hand, the age of the children and nasal allergy had no effect on the chances of biofilm formation.

Conclusions: This is a preliminary report showing that children exposed to household passive cigarette smoking may develop nasal biofilms. Development of these biofilms may increase susceptibility of affected children to persistent sinonasal and possibly other respiratory infections.
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http://dx.doi.org/10.1016/j.ijporl.2021.110755DOI Listing
July 2021

The impact of CBP expression in estrogen receptor-positive breast cancer.

Clin Epigenetics 2021 Apr 7;13(1):72. Epub 2021 Apr 7.

Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.

Background: The development of new biomarkers with diagnostic, prognostic and therapeutic prominence will greatly enhance the management of breast cancer (BC). Several reports suggest the involvement of the histone acetyltransferases CREB-binding protein (CBP) and general control non-depressible 5 (GCN5) in tumor formation; however, their clinical significance in BC remains poorly understood. This study aims to investigate the value of CBP and GCN5 as markers and/or targets for BC prognosis and therapy. Expression of CBP, GCN5, estrogen receptor α (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in BC was analyzed in cell lines by western blot and in patients' tissues by immunohistochemistry. The gene amplification data were also analyzed for CBP and GCN5 using the publicly available data from BC patients.

Results: Elevated expression of CBP and GCN5 was detected in BC tissues from patients and cell lines more than normal ones. In particular, CBP was more expressed in luminal A and B subtypes. Using chemical and biological inhibitors for CBP, ERα and HER2 showed a strong association between CBP and the expression of ERα and HER2. Moreover, analysis of the CREBBP (for CBP) and KAT2A (for GCN5) genes in a larger number of patients in publicly available databases showed amplification of both genes in BC patients. Amplification of CREBBP gene was observed in luminal A, luminal B and triple-negative but not in HER2 overexpressing subtypes. Furthermore, patients with high CREBBP or KAT2A gene expression had better 5-year disease-free survival than the low gene expression group (p = 0.0018 and p < 0.00001, respectively).

Conclusions: We conclude that the persistent amplification and overexpression of CBP in ERα- and PR-positive BC highlights the significance of CBP as a new diagnostic marker and therapeutic target in hormone-positive BC.
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http://dx.doi.org/10.1186/s13148-021-01060-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028106PMC
April 2021

Hepatic Injury in Neonates with Perinatal Asphyxia.

Glob Pediatr Health 2021 1;8:2333794X20987781. Epub 2021 Feb 1.

Benha University, Benha, Egypt.

Perinatal asphyxia (PA) is a major cause of morbidity and mortality in which dramatic transient impairment in liver functions occurs in some patients. We aimed to evaluate the state of the liver in cases of Perinatal asphyxia and to assess the severity of hepatic impairment in relation to different grades of HIE. This case-control study was conducted on 100 full-term newborns with perinatal asphyxia (Group I) and 50 healthy neonates served as controls (Group II). All biochemical parameters of liver function were measured on the 1st, 3rd, and 10th day after birth. These parameters include serum alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total protein, serum albumin, serum bilirubin (total and direct), and international normalized ratio (INR), in both cases and controls. Among babies with PA, 25 (25%) had an Apgar score of 0 to 3 (severe PA), 43 (43%) had an Apgar score of 4 to 5 (moderate PA) and 32 (32%) had an Apgar score of 6 to 7 (mild PA) at 5 minutes of life. HIE was found in 39% among cases of PA and the remaining 61% were normal. Among babies with PA and HIE; 25.7% had stage I, 41% had stage II and 33.3% had stage III. Impaired liver function was reported in 48% of asphyxiated babies. On the first day of life, ALT, AST, ALP, LDH, PT, and INR were significantly higher in Group I compared to Group II. However, total protein and serum albumin were significantly lower in Group I compared to Group II. ALT and AST showed a positive correlation with the severity of HIE. On the third day of life, LDH rises as the stage of HIE progressed from stage 0 to stage 3. The difference in LDH among most stages of HIE was statistically significant. Liver enzymes can be used as an easy early diagnostic marker to differentiate between babies with asphyxia and those without asphyxia. Also, liver enzymes can be used for the detection of the severity of PA.
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http://dx.doi.org/10.1177/2333794X20987781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868451PMC
February 2021

Immunohistochemical Assessment of TNFAIP3/A20 Expression Correlates With Early Tumorigenesis in Breast Cancer.

Anticancer Res 2021 Feb;41(2):739-745

Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

Background/aim: Limited data exist on the expression pattern of TNFAIP3/A20, as assayed by immunohistochemistry (IHC), in breast cancer tissues. This study aimed to assess A20 expression pattern in breast cancer.

Materials And Methods: The expression of A20 was analysed using IHC in 50 breast cancer cases retrieved from the Sharjah Breast Cancer Center at the University Hospital Sharjah, United Arab Emirates. Omics survival data were also used to analyse its association with survival in endocrine-treated subgroups.

Results: A20 expression in breast cancer tissues was 'tumor-specific', and as compared to normal tissue areas, its expression was associated with both intensity and extent in early grade 1 (p<0.0001) in all molecular subtypes. In addition, using omics survival data from a cohort of 3,520 breast cancer patients, we showed that A20 overexpression associated with lower overall survival rate in the endocrine treated subgroups [hazard ratio (HR)=2.14, 95%CI=1.61-2.82, p<0.0001].

Conclusion: A20 can serve as a biomarker for early diagnosis of breast cancers.
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http://dx.doi.org/10.21873/anticanres.14825DOI Listing
February 2021

M1 Polarization Markers Are Upregulated in Basal-Like Breast Cancer Molecular Subtype and Associated With Favorable Patient Outcome.

Front Immunol 2020 16;11:560074. Epub 2020 Nov 16.

Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.

Background: Breast cancer heterogeneity is an essential element that plays a role in the therapy response variability and the patient's outcome. This highlights the need for more precise subtyping methods that focus not only on tumor cells but also investigate the profile of stromal cells as well as immune cells.

Objectives: To mine publicly available transcriptomic breast cancer datasets and reanalyze their transcriptomic profiling using unsupervised clustering in order to identify novel subsets in molecular subtypes of breast cancer, then explore the stromal and immune cells profile in each subset using bioinformatics and systems immunology approaches.

Materials And Methods: Transcriptomic data from 1,084 breast cancer patients obtained from The Cancer Genome Atlas (TCGA) database were extracted and subjected to unsupervised clustering using a recently described, multi-step algorithm called Iterative Clustering and Guide-gene Selection (ICGS). For each cluster, the stromal and immune profile was investigated using ESTIMATE and CIBERSORT analytical tool. Clinical outcomes and differentially expressed genes of the characterized clusters were identified and validated and in a cohort of 80 breast cancer samples by immunohistochemistry.

Results: Seven unique sub-clusters showed distinct molecular and clinical profiles between the well-known breast cancer subtypes. Those unsupervised clusters identified more homogenous subgroups in each of the classical subtypes with a different prognostic profile. Immune profiling of the identified clusters showed that while the classically activated macrophages (M1) are correlated with the more aggressive basal-like breast cancer subtype, the alternatively activated macrophages (M2) showed a higher level of infiltration in luminal A and luminal B subtypes. Indeed, patients with higher levels of M1 expression showed less advanced disease and better patient outcomes presented as prolonged overall survival. Moreover, the M1 high basal-like breast cancer group showed a higher expression of interferon-gamma induced chemokines and guanylate-binding proteins (GBPs) involved in immunity against microbes.

Conclusion: Adding immune profiling using transcriptomic data can add precision for diagnosis and prognosis and can cluster patients according to the available modalities of therapy in a more personalized approach.
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http://dx.doi.org/10.3389/fimmu.2020.560074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701279PMC
May 2021

The synergistic hepatoprotective potential of Beta vulgaris juice and 2,3- dimercaptosuccinic acid in lead-intoxicated rats via improving the hepatic oxidative and inflammatory stress.

BMC Complement Med Ther 2020 Sep 1;20(1):268. Epub 2020 Sep 1.

Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt.

Background: Lead (Pb) is observed in all areas of the environment, mainly derived from human operations such as mining, processing, and burning fossil fuels. Pb toxicity is one of the most prevalent causes of human hepatotoxicity. The available chelator drugs used now have many adverse effects and therefore the world is looking for natural and secure alternatives.

Methods: Here, we evaluated the hepatoprotective role of the oral administration (1 g/kg b.w.) of the lyophilized Beta vulgaris juice (BVJ) against Pb-induced rat hepatotoxicity. We also examined the possible synergistic hepatoprotective impact of the combination between BVJ and 2,3- dimercaptosuccinic acid (DMSA, the currently approved drug for Pb-toxicity). The evaluation depends on the ability of BVJ, DMSA, or their combination (BVJ-DMSA) to reduce serum and hepatic Pb level and to avoid oxidative stress and inflammation caused by Pb. The level of lipid peroxidation, reduced glutathione (GSH), total antioxidant capacity, and the activity of the antioxidant enzymes were quantified. In addition, the level of interleukin (IL)-6, nitric oxide (NO), DNA fragmentation, and liver histology were studied.

Results: The results showed that BVJ contained considerable amounts of betalains, vitamin C, and various types of phenolic compounds. Therefore, BVJ displayed a significant (p < 0.05) preventive influence on the elevation of Pb levels in blood and liver as well as the hepatic DNA fragmentation. In addition, it significantly (p < 0.05) improved most of the studied antioxidant and inflammatory markers in the Pb-intoxicated rats. However, the combined extract (BVJ-DMSA) revealed synergistic (combination index < 1) activities in most of the tested parameters. The histopathological results verified the biochemical findings of this research.

Conclusion: BVJ has a potent efficiency in the protection from Pb-induced hepatotoxicity through the reduction of its accumulation in blood and liver and the prevention of the oxidative stress and inflammation induced by Pb. Additionally, the treatment of hepatotoxicity with BVJ and DMSA in combination showed a synergistic effect and reduced the adverse effects induced by DMSA. Thus, BVJ can be a promising hepatoprotective extract against lead toxicity and its combination with DMSA potentiates this effect.
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http://dx.doi.org/10.1186/s12906-020-03056-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466492PMC
September 2020

Bone marrow mammaglobin-1 (SCGB2A2) immunohistochemistry expression as a breast cancer specific marker for early detection of bone marrow micrometastases.

Sci Rep 2020 08 3;10(1):13061. Epub 2020 Aug 3.

Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Despite all the advances in the management of breast cancer (BC), patients with distance metastasis are still considered incurable with poor prognosis. For that reason, early detection of the metastatic lesions is crucial to improve patients' life span as well as quality of life. Many markers were proposed to be used as biomarkers for metastatic BC lesions, however many of them lack organ specificity. This highlights the need for novel markers that are more specific in detecting disseminated BC lesions. Here, we investigated mammaglobin-1 expression as a potential and specific marker for metastatic BC lesions using our patient cohort consisting of 30 newly diagnosed BC patients. For all patients, bone marrow (BM) aspiration, BM biopsy stained by H&E and BM immunohistochemically stained for mammaglobin-1 were performed. In addition, the CA15-3 in both serum and bone marrow plasma was also evaluated for each patient. Indeed, mammaglobin-1 immuno-staining was able to detect BM micrometastases in 16/30 patients (53.3%) compared to only 5/30 patients (16.7%) in BM biopsy stained by H&E and no cases detected by BM aspirate (0%). In addition, our results showed a trend of association between mammaglobin-1 immunoreactivity and the serum and BM plasma CA15-3. Further validation was done using large publicly available databases. Our results showed that mammaglobin-1 gene expression to be specifically upregulated in BC patients' samples compared to normal tissue as well as samples from other cancers. Moreover, our findings also showed mammaglobin-1 expression to be a marker of tumour progression presented as lymph nodes involvement and distant metastasis. These results provide an initial evidence for the use of mammaglobin-1 (SCGB2A2) immunostaining in bone marrow as a tool to investigate early BM micrometastases in breast cancer.
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http://dx.doi.org/10.1038/s41598-020-70012-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400628PMC
August 2020

Function of gold nanoparticles in oral cancer beyond drug delivery: Implications in cell apoptosis.

Oral Dis 2021 Mar 6;27(2):251-265. Epub 2020 Aug 6.

Department of Oral Pathology, Faculty of Dentistry, Alexandria University, Egypt.

Objectives: Gold nanoparticles (AuNPs) are used to deliver drugs and therapeutic small molecule inhibitors to cancer cells. Evidence shows that AuNPs coated with nuclear localization sequence can cross the nuclear membrane and induce cellular apoptosis. To determine the therapeutic role of AuNPs, we compared two nanoconstructs conjugated to doxorubicin (DOX) through pH-sensitive and pH-resistant linkers.

Materials And Methods: We tested DOX nanoconjugates' cytotoxicity, cellular and nuclear uptake in oral squamous cell carcinoma cell line. Furthermore, we evaluated the therapeutic effect of pH-sensitive and pH-resistant DOX bioconjugates in hamster buccal pouch carcinoma model.

Results: Our data indicate that pH-resistant and pH-sensitive DOX-nanoconjugates were equally localized in cancer cells, but the pH-resistant DOX nanoparticles were more localized in the nuclei inducing a 2-fold increase in the apoptotic effect compared with the pH-sensitive DOX nanoparticles. Our in vivo results show significantly higher tumor shrinkage and survival rates in animals treated with DOX pH-resistant AuNPs compared with pH-sensitive ones.

Conclusion: Our findings suggest that AuNPs enhance the cytotoxic effect against cancer cells in addition to acting as drug carriers. DOX pH-resistant AuNPs enhanced accumulation of AuNPs in cancer cells' nuclei inducing a significant cellular apoptosis which was confirmed using in vitro and in vivo experiments without deleterious effects on blood cell count.
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http://dx.doi.org/10.1111/odi.13551DOI Listing
March 2021

The prognostic value of ephrin type-A2 receptor and Ki-67 in renal cell carcinoma patients: An Immunohistochemical and Bioinformatical Approach; A STROBE - compliant article.

Medicine (Baltimore) 2020 May;99(19):e20191

Department of Pathology.

Patients with renal cell carcinoma (RCC), the most common malignant renal epithelial tumor, usually present with advanced disease and unpredicted clinical behavior. The receptor tyrosine kinase, ephrin type-A receptor 2 (EphA2) was found to be overexpressed in several malignancies and its expression was found to be associated with poor prognostic features.Our study is an observational study with the aim of investigating the prognostic value of EphA2 in RCC patients and its association with clinicopathological parameters as well as Ki-67 expression, which is a well-known proliferative and prognostic marker in RCC.EphA2 and Ki-67 immunohistochemical staining was performed on whole sections representative of 50 patients diagnosed with primary RCC from 2013 to 2018. In addition, the association between EphA2 mRNA expression and clinicopathological parameters as well as the patients' outcome was also evaluated using two large publicly available databases.Our results showed a significant association between EphA2 immunohistochemical expression and tumor size, nuclear grade, tumor stage, patients' outcome and Ki-67 expression (P < .05 for all). The same trend was also observed with EphA2 mRNA expression using larger patients' cohorts in 2 publicly available databases. Notably, EphA2 protein expression showed higher levels of co-expression with the proliferative marker Ki-67.Our results suggested that higher expression of EphA2 and Ki-67 in tumor tissues predicts a locally aggressive behaviour and poor outcome of patients with RCC. Moreover, our results give a rationale for the potential benefits of using novel therapeutic strategies with the aim of targeting EphA2 receptor in RCC patients that might help in improving their outcome.
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http://dx.doi.org/10.1097/MD.0000000000020191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220257PMC
May 2020

Quitting smoking reverses nasal mucosal changes.

Eur Arch Otorhinolaryngol 2020 Jun 12;277(6):1691-1698. Epub 2020 Mar 12.

LHI, Orlando, USA.

Background: Smoking, whether active or passive, has proven deleterious effects on the nasal mucosa. There is also a link between smoking and development and/or maintenance of chronic rhinosinusitis (CRS). Reversal of smoking-induced mucosal changes after quitting smoking is still unconfirmed and controversial. The present study investigated the possibility of reversal of smoking-related nasal mucosal changes back to normal after completely quitting smoking.

Methods: The study was performed on 32 smokers whose nasal mucosa was previously biopsied for electron microscopic examination and then they completely quit smoking. Smoking history of the participants and duration of cessation of smoking were recorded. A tiny 1-mm3 biopsy was taken from the inferior turbinate 1 cm behind its anterior end and processed for electron microscopy. The specimens were processed for electron microscopy and the sections were examined by a pathologist who was blinded to the identity and smoking status of the participant. The results of electron microscopic examination of the nasal mucosa before and after quitting smoking were compared.

Results: The mean duration of quitting smoking was 30.75 months (± 8.26). Examination of the electron microscopic sections before quitting smoking showed variable degrees of loss of cilia and columnar cells, edema between the epithelial cells, few goblet cells, hyperplasia of seromucinous acini, and vascular congestion. The pathologic changes correlated positively with the smoking index of the participant. On the other hand, the sections after quitting smoking showed variable degrees of regeneration of the ciliated cells and decreased vascular congestion. Numerous goblet cells and seromucinous acini were seen. Less pathologic changes were observed with longer durations of cessation of smoking.

Conclusions: The present study showed an association between smoking and the nasal mucosa. Smoking has several injurious effects on the nasal mucosa. However, the nasal mucosa has excellent regeneration potentials and quitting smoking for sufficient periods of time may reverse these deleterious changes. Considering the established link between smoking and CRS, quitting smoking may help smokers to overcome their recalcitrant disease. This should be further investigated.
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http://dx.doi.org/10.1007/s00405-020-05896-xDOI Listing
June 2020

Correlation of Insulin-like Growth Factor 1 Receptor Expression With Different Molecular Subtypes of Breast Cancer in the UAE.

Anticancer Res 2020 Mar;40(3):1555-1561

College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

Background: Insulin-like growth factor 1 receptor (IGF1R) activation triggers multiple signaling pathways involved in proliferation and anti-apoptosis in breast cancer (BC).

Materials And Methods: Immunohistochemistry for IGF1R was performed on 50 BC cases; expression was assessed for staining intensity and localization pattern (mixed, membranous, and cytoplasmic) which was correlated to hormone receptor status.

Results: Of estrogen receptor-positive (ER) cases, 97.2% were IGF1R (48.6% mixed, 43.2% membranous, and 5.4% cytoplasmic pattern) compared to ER cases (38.5%, 7.7% and 30.8%, respectively) (p=0.003). In progesterone receptor-positive (PR) cases, 97.2% were IGF1R, (47.2%, 41.7% and 8.3%, respectively) compared to PR ones (42.9%, 14.3% and 21.4%, respectively) (p=0.036). For human epidermal growth factor receptor 2-negative (HER2) cases, 88.8% were IGF1R (44.4%, 8.3% and 36.1%, respectively). All HER2 cases were IGF1R (71.4%, 7.1% and 21.4%, respectively) (p=0.015). In conclusion, hormone receptor-positive HER2 cases showed membranous and mixed IGF1R localization. However, hormone receptor-negative and HER2 showed cytoplasmic or diminished IGF1R expression.

Conclusion: These luminal subtypes may benefit from targeted IGFR therapy in the future.
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http://dx.doi.org/10.21873/anticanres.14102DOI Listing
March 2020

Potential Therapeutic Strategies for Lung and Breast Cancers through Understanding the Anti-Angiogenesis Resistance Mechanisms.

Int J Mol Sci 2020 Jan 15;21(2). Epub 2020 Jan 15.

College of Medicine, University of Sharjah, Sharjah 27272, UAE.

Breast and lung cancers are among the top cancer types in terms of incidence and mortality burden worldwide. One of the challenges in the treatment of breast and lung cancers is their resistance to administered drugs, as observed with angiogenesis inhibitors. Based on clinical and pre-clinical findings, these two types of cancers have gained the ability to resist angiogenesis inhibitors through several mechanisms that rely on cellular and extracellular factors. This resistance is mediated through angiogenesis-independent vascularization, and it is related to cancer cells and their microenvironment. The mechanisms that cancer cells utilize include metabolic symbiosis and invasion, and they also take advantage of neighboring cells like macrophages, endothelial cells, myeloid and adipose cells. Overcoming resistance is of great interest, and researchers are investigating possible strategies to enhance sensitivity towards angiogenesis inhibitors. These strategies involved targeting multiple players in angiogenesis, epigenetics, hypoxia, cellular metabolism and the immune system. This review aims to discuss the mechanisms of resistance to angiogenesis inhibitors and to highlight recently developed approaches to overcome this resistance.
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http://dx.doi.org/10.3390/ijms21020565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014257PMC
January 2020

Potential role for microRNA-16 (miR-16) and microRNA-93 (miR-93) in diagnosis and prediction of disease progression in mycosis fungoides in Egyptian patients.

PLoS One 2019 24;14(10):e0224305. Epub 2019 Oct 24.

Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Mycosis Fungoides (MF) is the most common type of cutaneous T-cell lymphomas. Early stage patients are treated with topical therapies and have normal life expectancy whereas patients with advanced disease encounter frequent relapses and have a five-year survival rate that does not exceed 15%. The aim of the present study was to characterize the expression of microRNA-16 (miR-16) and microRNA-93 (miR-93) in early and advanced cases of MF in relation to the clinicopathological parameters. Ten skin biopsies of early and advanced MF were investigated for the expression of miR-16 and miR-93 using RT-PCR. Immunohistochemical expression of apoptosis markers (BCL-2 and Survivin) were also investigated in the studied cases compared to normal skin and eczema biopsies. In the present study, BCL-2 and Survivin showed strong positive expression on neoplastic lymphocytes in all cases of MF regardless of their stage. We have also shown that miR-16 was significantly upregulated in advanced cases of MF compared to cases with early disease (p-value was less than 0.05). However, expression of miR-16 did not show any statistically significant correlation with age, gender, or expression of apoptotic markers. On the other hand, the expression of miR-93 showed significant downregulation in all lymphoma cases irrespective of their stage, compared to normal and eczema cases. Our results suggest that upregulation of miR-16 could be used to predict an aggressive course of the disease. We also suggest that miR-93 downregulation could serve as possible tool for establishing early diagnosis in early challenging cases. Our findings also provide consistent evidence that the anti-apoptotic molecules may play an important role in the pathogenesis of this type of cutaneous lymphomas and promote the idea that their inhibition could be an interesting novel therapeutic strategy in the treatment of MF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224305PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812867PMC
March 2020

Serum Neuron-specific Enolase and S100 Calcium-binding Protein B in Pediatric Diabetic Ketoacidosis

J Clin Res Pediatr Endocrinol 2019 11 9;11(4):374-387. Epub 2019 May 9.

Benha University Faculty of Medicine, Department of Clinical Pathology, Benha, Egypt

Objective: Neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) are markers of different neurological disorders. The aim was to investigate the relationship between NSE and S100B serum concentrations and the severity of diabetic ketoacidosis (DKA) in diabetic children.

Methods: Eighty children with DKA, 40 with type 1 diabetes mellitus (T1DM) without DKA and 40 healthy controls were enrolled. Severity of DKA was assessed according to blood pH and bicarbonate concentration. Serum NSE and S100B were measured in all participants. In the DKA group serum NSE and S100B were measured at three time points, at admission and at 12 hours and 24 hours after starting treatment.

Results: Children with DKA showed significantly higher serum levels of NSE at all time points compared to children with T1DM without DKA and controls (p<0.01), while serum S100B concentrations did not differ between the three cohorts. Children with T1DM but without DKA also had significantly higher serum levels of NSE (p<0.01) compared to healthy controls. Patients with low Glasgow Coma Scale score (GCSS) and those with moderate and severe DKA had significantly higher levels of NSE at all time points (p<0.01 for each) compared to patients with normal GCSS and those with mild DKA. No significant differences were found in serum S100B levels according to the severity of DKA and GCS (p>0.05). Younger age, lower GCSS, higher glucose and HbA1c, lower pH and lower serum bicarbonate were the risk factors associated with elevated NSE.

Conclusion: Serum NSE is elevated in all patients with type 1 DM and, in patients with DKA, correlates with severity of DKA. However, serum S100B concentration did not differ between T1DM with or without DKA and healthy controls.
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http://dx.doi.org/10.4274/jcrpe.galenos.2019.2018.0280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878350PMC
November 2019

Correlation of securin and Ki67 in invasive breast carcinoma.

Histol Histopathol 2019 Jun 3;34(6):697-709. Epub 2018 Dec 3.

Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Aims: To identify the role of securin (PTTG) as a prognostic marker in invasive breast carcinoma and its possible relation to ki67 and to evaluate the use of ImmunoRatio® as a tool for calculating ki67 and securin labelling indices.

Methods: Securin and ki67 immunohistochemical staining were performed on tissue microarray sections representative of 118 patients diagnosed with invasive breast carcinoma from 2005 to 2011. Assessment of immunohistochemical staining was carried out using both visual counting and ImmunoRatio®. The 118 cases were categorized into 2 groups according to their clinical outcome; the first group (G1) (n=77) comprised patients who were disease-free while the second group (G2) (n=41) included patients who developed either recurrence and/or metastasis at the end of 24 months follow-up duration.

Results: Both securin and ki67 labelling indices (LIs) obtained by visual counting were significantly higher in G2, while only securin LIs acquired by ImmunoRatio® were significantly higher in G2. Securin assessment by visual counting was the most accurate (AUC=0.775) in identifying patients who will likely suffer from recurrence and/or distant metastasis. Pearson correlation showed r=0.638, p<0.001 for Ki67 and r=0.671, p<0.001 for securin. Linear regression analysis showed a significant correlation between ki67 and securin, B=1.75, p<0.001.

Conclusion: The present results suggest that securin may add to the prognostic value of ki67 in highlighting intra-tumoural heterogeneity in invasive breast carcinoma patients with poor clinical outcome. In addition, the study showed that since securin has a visual counting cutoff with more than 1%, making it easier to use as a breast cancer biomarker in conjunction with ki67 to predict the outcome of the cases more accurately than using only ki67. However, a multivariate analysis on a larger cohort of patients is mandatory to test its potential prognostic value.
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http://dx.doi.org/10.14670/HH-18-071DOI Listing
June 2019

Effect of oral isotretinoin on the nucleo-cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris.

Exp Dermatol 2018 12 17;27(12):1344-1351. Epub 2018 Oct 17.

Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany.

Oral isotretinoin is the most effective anti-acne drug with the strongest sebum-suppressive effect caused by sebocyte apoptosis. It has been hypothesized that upregulation of nuclear FoxO transcription factors and p53 mediate isotretinoin-induced sebocyte apoptosis in vivo. It is the aim of our study to analyse the distribution of the pro-apoptotic transcription factors FoxO1 and FoxO3 in the nuclear and cytoplasmic compartments of human sebocytes in vivo before and during isotretinoin treatment of acne patients. Immunohistochemical analysis of skin biopsies with antibodies distinguishing phosphorylated and non-phosphorylated human FoxO1 and FoxO3 proteins was performed before isotretinoin treatment, six weeks after initiation of isotretinoin therapy, and in acne-free control patients not treated with isotretinoin. Our in vivo study demonstrates a significant increase in the nucleo-cytoplasmic ratio of non-phosphorylated FoxO1 and FoxO3 during isotretinoin treatment of acne patients. Translational and presented experimental evidence indicates that upregulation of nuclear FoxO1 and FoxO3 proteins is involved in isotretinoin-induced pro-apoptotic signalling in sebocytes confirming the scientific hypothesis of isotretinoin-mediated upregulation of FoxO expression.
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http://dx.doi.org/10.1111/exd.13787DOI Listing
December 2018

Clinical characteristics and aetiology of early childhood epilepsy: a single centre experience in Saudi Arabia.

Sudan J Paediatr 2018 ;18(1):57-62

Paediatric Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

Seizures in children and neonatal period have variety of causes; however, most of childhood seizures are idiopathic. The aim of this study was to review the causes of epilepsy in children presenting in the first 2 years of life using the International League Against Epilepsy classification released in 2010. This was a retrospective chart review study that was conducted at a tertiary center in Saudi Arabia. Two hundred and twenty-one patients were included in the study, 31 with conditions mimic epilepsy were excluded. The remaining 190 patients were classified into: Group A, structural/metabolic, 82 (43%); Group B, genetic, 24 (13%) and Group C, unknown, 84 (44%). The commonest seizures' type was tonic-clonic in 106 (56%), followed by clonic 29 (15.3%), myoclonic 22 (11.6%) and a tonic 16 (8.4%). Pyramidal signs, global developmental delay, hypotonia, micro/macrocephaly and abnormal computed tomography and/or magnetic resonance imaging brain were more common in the structural/metabolic group ( < 0.05). Electroencephalography was abnormal in 136 (72%) patients, mostly in the structural/metabolic group ( = 0.011). In conclusion, the aetiology of epilepsy in this cohort was mainly unknown or secondary to structural/metabolic causes.
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http://dx.doi.org/10.24911/SJP.2018.1.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113787PMC
January 2018

The Potential Role of PTPN-22 C1858T Gene Polymorphism in the Pathogenesis of Type 1 Diabetes in Saudi Population.

Immunol Invest 2018 Jul 3;47(5):521-533. Epub 2018 Apr 3.

i Department of Microbiology and Immunology , College of Medicine, Taif University , Taif , Saudi Arabia.

Background: Recent investigations have reported an association between protein tyrosine phosphatase non-receptor type-22 (PTPN-22) gene polymorphism and susceptibility to the development of type 1 diabetes (T1D) in some populations and not in others. In this study, we aimed to investigate the association of PTPN-22 C1858T polymorphism with T1D in Saudi children.

Methods: A cohort of 372 type 1 diabetic children and 372 diabetes-free subjects was enrolled in the current investigation. The PTPN-22 C1858T polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: Our data showed that the frequency of CT and TT genotypes of PTPN-22 C1858T was higher in T1D children (17.7% and 4.3%, respectively) compared to healthy controls (4.8% and 1.6%, respectively), and both genotypes were statistically associated with T1D patients (OR = 4.4, 95% CI: 2.55-7.58, p < 0.001; and OR = 3.2, 95% CI: 1.23-8.28, p = 0.017, respectively). Moreover, the 1858T allele was significantly associated with T1D patients compared to the C allele (OR = 3.2, 95% CI: 1.59-6.88, p < 0.001). In addition, the T allele was significantly associated with elevated levels of HbA1c, anti-GAD, and anti-insulin antibodies (p < 0.001) and a lower concentration of C-peptide (p < 0.001) in T1D children.

Conclusion: The data presented here suggests that the T allele of PTPN-22 C1858T polymorphism might be a risk factor for T1D development in Saudi children.
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http://dx.doi.org/10.1080/08820139.2018.1458109DOI Listing
July 2018

Association between cytokine genes polymorphisms and type 1 diabetes: a case-control study on Saudi population.

Immunol Invest 2018 Apr 19;47(3):229-240. Epub 2017 Dec 19.

h Department of Pediatrics , College of Medicine, Taif University , Taif , Saudi Arabia.

Background: Association studies of genes encoding cytokines that play an important role in inflammatory response represent one approach to finding type 1 diabetes (T1D) disease genes. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) within cytokine genes with T1D in a cohort of Saudi subjects.

Methods: A total of 300 well-characterized type 1 diabetic patients and 300 T1D-free control subjects were enrolled in this investigation. Cytokine SNPs were genotyped by using Polymerase chain reaction (PCR) with sequence-specific primers.

Results: Our data revealed that IFN-γ +874T allele carriers [odds ratio (OR) = 1.87, p < 0.001] and TT homozygotes (OR = 1.28, p < 0.001) were significantly more susceptible to developing T1D than the A allele carriers. In addition, TNF-α -308A allele carriers (OR = 1.73, p < 0.001) and AA homozygotes (OR = 1.74, p < 0.001) were also overrepresented among the diabetics than G allele carriers. IL-4 -590C/T TT homozygotes (OR = 2.23, p < 0.001) were significantly more susceptible to develop T1D than CC genotypes, whereas CT heterozygotes were not significantly associated (OR = 1.43, p = 0.78) with T1D. Furthermore, IL-4 T allele was statistically associated with T1D patients compared to control group (OR = 2.24, p < 0.001). Similarly, IL-1β -511C/T TT homozygotes (OR = 1.85, p = 0.012) and the T allele (OR = 1.85, p < 0.001) were significantly more susceptible to T1D than CC genotypes, whereas TC heterozygotes (OR = 1.04, p = 0.86) were not significantly associated with T1D.

Conclusion: Our data concluded that IFN-γ +874T allele, TNF-α -308A allele, IL-1β -511T allele, and IL-4 -590T allele could be considered risk factors for T1D development in Saudi subjects.
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http://dx.doi.org/10.1080/08820139.2017.1416398DOI Listing
April 2018

Screening of gene sequence variants in Saudi Arabian children with idiopathic short stature.

Korean J Pediatr 2017 Oct 20;60(10):327-332. Epub 2017 Oct 20.

Deanship of Scientific Research, Taif University, Taif, Saudi Arabia.

Purpose: Short stature affects approximately 2%-3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene () are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of to identify related mutations.

Methods: We screened all the exons of for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated.

Results: A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in .

Conclusion: In Saudi Arabia ISS patients, rather than , it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.
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http://dx.doi.org/10.3345/kjp.2017.60.10.327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687980PMC
October 2017

Orthodontically induced osteocyte apoptosis under different force magnitudes in rats: an immunohistochemical study.

Eur J Oral Sci 2017 10 8;125(5):361-370. Epub 2017 Aug 8.

Department of Orthodontics, Faculty of Dentistry, Alexandria University, Alexandria, Egypt.

We investigated the effect of different force magnitudes on osteocyte apoptosis in a model of orthodontic tooth movement. Forty-nine male Sprague Dawley rats (7-9 wk of age) were divided into light- and heavy-force groups (n = 21 each group) and a control group (n = 7). A coil spring delivered pressure (either 10-15 g or 20-25 g) to the left maxillary first molar. The rats were sacrificed 1, 3, or 5 d after placement of the appliance. Sections of the maxillary first molars were immunostained for caspase-3. Upon force application, the number of apoptotic osteocytes significantly increased in the pressure side at 1 d and remained the same at 3 d and 5 d. However, there was no significant difference in the number of apoptotic osteocytes between the two force groups. We conclude that osteocyte apoptosis appears to increase under orthodontic loading, reaching a plateau after 1 d. However, osteocyte apoptosis seems to be independent of the magnitude of orthodontic forces tested.
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http://dx.doi.org/10.1111/eos.12366DOI Listing
October 2017

A randomized clinical trial comparing 3 different replacement regimens of vitamin D in clinically asymptomatic pediatrics and adolescents with vitamin D insufficiency.

Ital J Pediatr 2016 Dec 7;42(1):106. Epub 2016 Dec 7.

Laboratory department, Prince Mansour Military Community Hospital, Taif, KSA, Saudi Arabia.

Background: Pediatric and Adolescent populations both have special needs for vitamin D especially for growing bone. Inadequate vitamin D is defined as 25 (OH) D(25hydroxy vitamin D) < 30 ng/ml.

Methods: We conducted a randomized, controlled clinical trial from July 2014 over 1 year, aiming to assess the changes in 25 (OH) D and biochemical outcome on calcium and PTH(parathyroid hormone) using 3 different regimens of vitamin D replacement. Initial and 4 month 25 (OH) D, calcium, PTH and 12 month 25 (OH) D levels were assayed. Participants divided into 3 groups: 1) given 400 IU daily, 2) given 45000 IU weekly for 2 months then 400 IU daily, 3) given 2000 IU daily for 3 months then 1000 IU daily.

Results: The results showed significant difference between the 3 groups as regards 25 (OH) D at 4 and 12 months (P < 0.001). Regimens used in group 2 and 3 caused increase in 25 (OH) D after 4 month (median increase is 225% and 200% respectively). 25 (OH) D dropped in group 1 and 2 (median decrease is 42 and 53% respectively) but continued to increase in group 3 (median change is 6%). In group 2 serum calcium median change was 1.2% with few cases of hypercalcuria. 94.9, 76.1 and 7.7 are the percent of vitamin D deficient participants in groups 1, 2 and 3 respectively after 12 months follow up.

Conclusion: We advise as a replacement for vitamin D insufficiency, low loading dose with high maintaince dose rather than the opposite to achieve steady increase in serum 25 (OH) D with no hypercalcemic side effects.
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http://dx.doi.org/10.1186/s13052-016-0314-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142392PMC
December 2016

The effect of chitosan nanospheres on the immunogenicity of Toxoplasma lysate vaccine in mice.

J Parasit Dis 2016 Sep 5;40(3):611-26. Epub 2014 Sep 5.

Department of Medical Parasitology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.

Toxoplasmosis, a zoonotic parasitic disease, is a huge challenge for which there is no effective vaccine up till now. In this study, chitosan nanospheres encapsulated with Toxoplasma lysate vaccine was evaluated for its ability to protect mice against both acute and chronic toxoplasmosis models of infection. Results showed that chitosan nanospheres were equally effective to Freund's incomplete adjuvant (FIA) in enhancing the efficacy of Toxoplasma lysate vaccine. The effectiveness was demonstrated by the delayed death of vaccinated mice following challenge either with virulent RH or avirulent Me49 strains, the significant decrease in parasite density in different organs, significant increase in the humoral and cellular immune response (IgG and IFN γ) with a marked reduction of pathological changes in the different organs. However chitosan nanospheres were superior to FIA due to their cost effective preparation and much less necrotic changes induced in the studied organs. The success of chitosan polymer as an alternative to commonly used adjuvants paves the way for the use of other newly developed polymers to be used in the field of vaccine development.
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http://dx.doi.org/10.1007/s12639-014-0546-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996159PMC
September 2016

Role of bacterial biofilm in development of middle ear effusion.

Eur Arch Otorhinolaryngol 2016 Nov 27;273(11):4003-4009. Epub 2016 May 27.

Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Alexandria University, 8 El Gesh St, El Azareeta, Alexandria, Egypt.

Biofilms have been implicated in the development of several chronic upper respiratory tract infections. Role of bacterial biofilms has been well studied in the pathogenesis of chronic rhinosinusitis. However, its impact on development of middle ear effusion is still a matter of debate. To study the extent of surface adenoid biofilm and evaluate its role in the pathogenesis of chronic otitis media with effusion in children. The study was carried out on 40 children in Alexandria Main University Hospital between 1 and 16 years of age without sex predilection, who were divided into two groups. The first group (20 children) had otitis media with effusion associated with adenoid hypertrophy, whereas the second group (20 children) had adenoid hypertrophy without middle ear effusion. Adenoidectomy with ventilation tube insertion was done for group 1 cases, whereas, only Adenoidectomy was done for group 2 cases. The samples were processed for the detection of biofilms by scanning electron microscopy. The biofilm formation was graded according to extension. Biofilm formation was detected on all samples for group 1. Adenoids removed from patients with otitis media with effusion had higher-grade biofilm formation than the other group (P 0.0001). No correlation was found between adenoid size and biofilm formation. In pediatric population, adenoid surface biofilm formation may be involved in the pathogenesis otitis media with effusion.
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http://dx.doi.org/10.1007/s00405-016-4094-2DOI Listing
November 2016

Prevalence of human papilloma virus (HPV) and its genotypes in cervical specimens of Egyptian women by linear array HPV genotyping test.

Infect Agent Cancer 2016 17;11. Epub 2016 Feb 17.

Department of obstetrics& gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background: The association of human papillomavirus (HPV) with cervical cancer is well established.

Aim: To investigate HPV genotype distribution and co-infection occurrence in cervical specimens from a group of Egyptian women.

Methods: A group of 152 women with and without cervical lesions were studied. All women had cervical cytology and HPV testing. They were classified according to cytology into those with normal cytology, with squamous intraepithelial lesions (SIL) and invasive squamous cell carcinoma (SCC). Cervical samples were analyzed to identify the presence of HPV by PCR, and all positive HPV-DNA samples underwent viral genotype analysis by means of LINEAR ARRAY HPV Genotyping assay.

Results: A total of 26 HPV types with a prevalence of 40.8 % were detected. This prevalence was distributed as follows: 17.7 % among cytologically normal females, 56.5, 3.2, and 22.6 % among those with LSIL, HSIL and invasive SCC respectively. Low-risk HPV types were detected in 81.8 % of the cytologically-normal women, in 5.7 % of those in LSIL women, and in 14.3 % of infections with invasive SCC, while no low-risk types were detected in HSIL. High-risk HPV types were detected in 18.2 % of infections in the cytologically normal women, 14.3 % of infections in LSIL, and in 21.4 % of invasive lesions. The probable and possible carcinogenic HPV were not detected as single infections. Mixed infection was present in 80 % of women with LSIL, in 100 % of those with HSIL, and in 64.3 % of those with invasive SCC. This difference was statistically significant. HPV 16, 18 and 31 were the most prevalent HR HPV types, constituting 41.9, 29.03 and 12.9 % respectively, and HPV 6, 62 and CP6108 were the most prevalent LR HPV types constituting 11.3, 9.7 and 9.7 % respectively.

Conclusion: These data expand the knowledge concerning HPV prevalence and type distribution in Egypt which may help to create a national HPV prevention program. HPV testing using the LINEAR ARRAY HPV Genotyping assay is a useful tool when combined with cytology in the diagnosis of mixed and non-conventional HPV viral types.
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http://dx.doi.org/10.1186/s13027-016-0053-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756400PMC
February 2016

Combination between Taxol-Encapsulated Liposomes and Eruca sativa Seed Extract Suppresses Mammary Tumors in Female Rats Induced by 7,12 Dimethylbenz(α)anthracene.

Asian Pac J Cancer Prev 2016 ;17(1):117-23

Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt E-mail :

Taxol (paclitaxel) is a powerful anti-cancer drug widely used against several types of malignant tumors. Because Taxol may exert several side effects, a variety of formulations have been developed. One of these features liposomes, regarded as one of the most promising drug carriers, biocompatible and best able to reduce drug toxicity without changing efficacy against tumor cells. Eruca sativa seed extract (SE) is considered a promising natural product from cruciferous vegetables against breast cancer, increasing chemotherapeutic and eliminating harmful side effects. The effects of Taxol-encapsulated liposomes (T) alone and in combination between Eruca sativa seed extract on nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels were investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(α) anthracene (DMBA) using qRT-PCR. The results showed that DMBA increased NF-κB, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while decreasing glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. T and T-SE treatment reduced NF-κB, COX-2 and Bcl-2 gene expression levels and LP. Hence, T and T-SE treatment appeared to reduce inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC.
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http://dx.doi.org/10.7314/apjcp.2016.17.1.117DOI Listing
December 2016

Inhibition of NF-κB, Bcl-2 and COX-2 Gene Expression by an Extract of Eruca sativa Seeds during Rat Mammary Gland Carcinogenesis.

Asian Pac J Cancer Prev 2015 ;16(18):8411-8

Department of Nucleic Acid Research, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, Alexandria, Egypt E-mail :

The effect of Eruca sativa seed extract (SE) on nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels was investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(α)anthracene (DMBA). DMBA increased NF-κB, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while, decreased glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. After DMBA administration, SE treatment reduced NF-κB, COX-2 and Bcl-2 gene expression levels and LP. Hence, SE treatment reduced inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC. Analysis revealed that SE has high concentrations of total flavonoids, triterpenoids, alkaloids and polyphenolic compounds such as gallic, chlorogenic, caffeic, 3,4-dicaffeoyl quinic, 3,5-dicaffeoyl quinic, tannic, cinnamic acids, catechin and phloridzin. These findings indicate that SE may be considered a promising natural product from cruciferous vegetables against breast cancer, especially given its high antioxidant properties.
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http://dx.doi.org/10.7314/apjcp.2015.16.18.8411DOI Listing
October 2016

First report of co-morbidity of pantothenate kinase-associated neurodegeneration and three types of chronic hemolytic anemias.

Ann Med Surg (Lond) 2016 Feb 10;5:11-3. Epub 2015 Nov 10.

Prince Mansour Hospital, Taif, Saudi Arabia.

Background: Pantothenate kinase-associated neurodegeneration (PKAN), sickle cell anemia, and thalassemia are autosomal recessive disorders that can cause iron deposition in tissues during childhood. PKAN is characterized by accumulation of iron in the basal ganglia causing progressive extrapyramidal manifestations. Thalassemia and sickle cell disease can cause iron overload and deposition in tissues, including central nervous system.

Presentation Of Case: we herein report the first report of comorbidity of PKAN, β-thalassemia-major, sickle cell and glucose-6-phosphate dehydrogenase deficiency (G6PD) anemias in a 9 years old Saudi female patient who presented with gait disturbance, speech difficulty, and progressive movement disorders of the neck, upper and lower limbs.

Conclusion: Although extremely rare, β-thalassemia-major, sickle cell and G6PD anemias can be associated with PKAN. It is unknown whether this association is random or due to an unknown factor that may have caused several mutations.
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http://dx.doi.org/10.1016/j.amsu.2015.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680082PMC
February 2016

Neurometabolic Disorders-Related Early Childhood Epilepsy: A Single-Center Experience in Saudi Arabia.

Pediatr Neonatol 2015 Dec 28;56(6):393-401. Epub 2015 Apr 28.

Ophthalmic Genetics Laboratory, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Background: Data on the pattern of epilepsy caused by metabolic disorders in the first 2 years of life are limited in developing countries. We aimed to identify the metabolic causes of epilepsy presented in the first 2 years of life and to describe their clinical, radiological, molecular, and electroencephalographic characteristics.

Methods: This retrospective study was conducted between January 2010 and December 2011 at Saad Specialist Hospital (Al Khobar, Saudi Arabia). All patients younger than 2 years at the onset of epilepsy caused by metabolic disorders were reviewed. The International League Against Epilepsy definition was used, and febrile convulsion was excluded.

Results: Of 221 children diagnosed with epilepsy in the first 2 years of life at our hospital, 24 had metabolic diseases. The characteristics of these 24 children included the following: consanguinity in 18 patients (75%), developmental delay in 13 (54%), generalized tonic-clonic seizures in 10 (42%), infantile spasms in four (17%), myoclonic in seven (29%), and focal seizures in three. The diagnosis was confirmed by DNA studies in 17 patients (71%) and enzyme assay in seven (29%). The main diagnoses were peroxisomal disorders (n = 3), nonketotic hyperglycinemia (n = 3), Menkes disease (n = 2), neuronal ceroid lipofuscinosis (n = 2), biotinidase deficiency (n = 2), and mitochondrial disorder (n = 2). The remaining patients had lysosomal storage disease, aminoacidopathy, fatty acid oxidation defects, and organic aciduria. Seizure freedom was achieved in one third of patients in this cohort.

Conclusion: Different metabolic disorders were identified in this cohort, which caused different types of epilepsy, especially myoclonic seizures and infantile spasms.
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http://dx.doi.org/10.1016/j.pedneo.2015.02.004DOI Listing
December 2015

Changes in growth, hormones levels and essential oil content of Ammi visnaga L. plants treated with some bioregulators.

Saudi J Biol Sci 2014 Sep 19;21(4):355-65. Epub 2013 Nov 19.

Botany Department, National Research Centre, Cairo, Egypt.

The effects of foliar application of different concentrations of amino acids (tyrosine and phenylalanine) and phenolic acids (trans-cinnamic acid, benzoic acid and salicylic acid) on growth, pigment content, hormones levels and essential oil content of Ammi visnaga L were carried out during two successive seasons. It is clear that foliar application of either amino acids or phenolics significantly promoted the growth parameters in terms of shoot height, fresh and dry biomass, number of branches and number of umbels per plant. The increment of growth parameter was associated with elevated levels of growth promoters (IAA, GA3, total cytokinins) and low level of ABA. The greatest increase in the previously mentioned parameters was measured in plants exposed to different concentrations of phenols particularly in benzoic acid-treated plants. Such effect was concentration dependent. All treatments led to significant increments in yield seeds and oil content. Moreover, gas liquid chromatographic analysis revealed that the main identified components of essential oil were 2,2-dimethyl butanoic acid, isobutyl isobutyrate, α-isophorone, thymol, fenchyl acetate and linalool. Phenolics and amino acid treatments resulted in qualitative differences in these components of essential oil.
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http://dx.doi.org/10.1016/j.sjbs.2013.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150225PMC
September 2014