Papers by Nourhan Abu Shahba
European Journal of Medical Genetics, 2011
Hereditary spastic paraplegia (HSP) represents a large group of neurological disorders characteri... more Hereditary spastic paraplegia (HSP) represents a large group of neurological disorders characterized by progressive spasticity of the lower limbs. One subtype of HSP shows an autosomal recessive form of inheritance with this corpus callosum (ARHSP-TCC), and displays genetic heterogeneity with four known loci. We identified a consanguineous Egyptian family with five affected individuals with ARHSP-TCC. We found linkage to the SPG11 locus and identified a novel homozygous p.Q498X stop codon mutation in exon 7 in the SPG11 gene encoding Spatacsin. Cognitive impairment and polyneuropathy, reported as frequent in SPG11, were not evident. This family supports the importance of SPG11 as a frequent cause for ARHSP-TCC, and expands the clinic SPG11 spectrum.
Cancer Informatics
Abnormal miRNA expression has been evidenced to be directly linked to HCC initiation and progress... more Abnormal miRNA expression has been evidenced to be directly linked to HCC initiation and progression. This study was designed to detect possible prognostic, diagnostic, and/or therapeutic miRNAs for HCC using computational analysis of miRNAs expression. Methods: miRNA expression datasets meta-analysis was performed using the YM500v2 server to compare miRNA expression in normal and cancerous liver tissues. The most significant differentially regulated miRNAs in our study undergone target gene analysis using the mirWalk tool to obtain their validated and predicted targets. The combinatorial target prediction tool; miRror Suite was used to obtain the commonly regulated target genes. Functional enrichment analysis was performed on the resulting targets using the DAVID tool. A network was constructed based on interactions among microRNAs, their targets, and transcription factors. Hub nodes and gatekeepers were identified using network topological analysis. Further, we performed patient d...
Azhar International Journal of Pharmaceutical and Medical Sciences
Adipose tissue is a readily available and plentiful source of multipotent mesenchymal stromal/ste... more Adipose tissue is a readily available and plentiful source of multipotent mesenchymal stromal/stem cells (AT-MSC). The immunomodulatory properties of AT-MSC are being introduced in type 2 diabetes (T2D) cell-based therapy. The study aimed to uncover the impact of T2D, on the interplay between AT-MSC and immune cells to develop an effective and safe AT-MSC immunotherapeutic modality. Thus, a direct allogenic co-culture of healthy AT-MSC (nAT-MSC) and peripheral blood mononuclear cells (PBMC), from healthy (nPBMC) or T2D (dPBMC) donors, and stimulated with anti-CD3/CD28, was established in vitro. PBMC proliferation was evaluated by measuring 5-bromo-20-deoxyuridine (Brdu) incorporation in the DNA of proliferating cells in a colorimetric ELISA assay. Expression levels of CD3 + T cell activation surface markers (CD25 and HLA-DR) were detected using a flow cytometer. As well, the anti-proliferative effect of naïve and interferon gamma (IFN-ɤ)-primed AT-MSC, isolated from T2D patients (dAT-MSC), on autologous PBMC was explored using the Brdu proliferation assay. In the applied co-culture setting, the diabetic milieu does not significantly impact the potential of nAT-MSC to suppress stimulated PBMC proliferation. However, it significantly compromises nAT-MSC ability to modulate the activation markers expression, making them less potent to suppress CD25 and HLA-DR expression. Moreover, the dAT-MSC have attenuated ability to suppress the proliferation of autologous stimulated dPBMC, nevertheless, priming of dAT-MSC with IFN-ɤ, might improve such defect. The results suggest that T2D might affect the immunosuppressive potential of AT-MSC and pre-conditioning of dAT-MSC with a pro-inflammatory stimulus could enhance their therapeutic effect.
Stem Cells International, 2016
The effect of mesenchymal stem cells (MSCs) on bone formation has been extensively demonstrated t... more The effect of mesenchymal stem cells (MSCs) on bone formation has been extensively demonstrated through severalin vitroandin vivostudies. However, few studies addressed the effect of MSCs on osteoclastogenesis and bone resorption. Under physiological conditions, MSCs support osteoclastogenesis through producing the main osteoclastogenic cytokines, RANKL and M-CSF. However, during inflammation, MSCs suppress osteoclast formation and activity, partly via secretion of the key anti-osteoclastogenic factor, osteoprotegerin (OPG).In vitro, co-culture of MSCs with osteoclasts in the presence of high concentrations of osteoclast-inducing factors might reflect thein vivoinflammatory pathology and prompt MSCs to exert an osteoclastogenic suppressive effect. MSCs thus seem to have a dual effect, by stimulating or inhibiting osteoclastogenesis, depending on the inflammatory milieu. This effect of MSCs on osteoclast formation seems to mirror the effect of MSCs on other immune cells, and may be e...
Copyright © 2016 Wessam E. Sharaf-Eldin et al.This is an open access article distributed under th... more Copyright © 2016 Wessam E. Sharaf-Eldin et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the originalwork is properly cited. The effect of mesenchymal stem cells (MSCs) on bone formation has been extensively demonstrated through several in vitro and in vivo studies. However, few studies addressed the effect of MSCs on osteoclastogenesis and bone resorption. Under physiological conditions, MSCs support osteoclastogenesis through producing the main osteoclastogenic cytokines, RANKL and M-CSF. However, during inflammation, MSCs suppress osteoclast formation and activity, partly via secretion of the key anti-osteoclastogenic factor, osteoprotegerin (OPG). In vitro, co-culture ofMSCs with osteoclasts in the presence of high concentrations of osteoclast-inducing factors might reflect the in vivo inflammatory pathology and prompt MSCs to exert an osteoclasto...
Genes & Nutrition, 2020
Background MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and ... more Background MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and have been approved to play a role in obesity. Despite several studies have focused on microRNA expression profiles and functions in different metabolic tissues, little is known about their response to nutritional interventions in white adipose tissue during obesity stages, and whether they differ in this response to weight-reduction strategy is poorly understood. Our objectives were to study the dysregulation of some miRNAs in subcutaneous inguinal white adipose tissue during weight change, expansion/reduction; in response to both a high-fat diet and switching to a normal diet feeding, and to evaluate them as potential biomarkers and therapeutic targets for early obesity management Method A hundred 6-week-old male Wister rats were randomly divided into a normal diet group (N.D), a high-fat diet group (H.F.D), and a switched to a normal diet group (H.F.D/N.D). At the beginning and at inte...
Cell Regeneration
Background Adipose-derived stem cells (ASCs) are considered ideal candidates for both research an... more Background Adipose-derived stem cells (ASCs) are considered ideal candidates for both research and cellular therapy due to ease of access, large yield, feasibility, and efficacy in preclinical and clinical studies. Unlike the subcutaneous abdominal fat depot, breast ASCs features are still not well recognized, limiting their possible therapeutic use. ASCs were found to exert immunomodulatory and antioxidative activities for maintaining homeostasis and functionality of diseased/damaged tissues. This study aims to investigate the immunomodulatory and antioxidative potentials of breast versus abdominal isolated ASCs to find out which anatomical site provides ASCs with better immunoregulatory and oxidative stress resistance capabilities. Methods ASCs were isolated from abdominal and breast tissues. Gene expression analysis was conducted for a panel of immunomodulatory and antioxidative genes, as well as adipokines and proliferation genes. Flow cytometric analysis of a group of immunomod...
The International Journal of Biochemistry & Cell Biology
Scientific Reports
Hepatic cancer stem cells (HCsCs) are considered as main players for the hepatocellular carcinoma... more Hepatic cancer stem cells (HCsCs) are considered as main players for the hepatocellular carcinoma (HCC) initiation, metastasis, drug resistance and recurrence. there is a growing evidence supporting the down-regulated miRNAs in HCsCs as key suppressors for the stemness traits, but still more details are vague about how these miRNAs modulate the HCC development. to uncover some of these miRNA regulatory aspects in HCSC, we compiled 15 down-regulated miRNA and their validated and predicted up-regulated targets in HCsC. the targets were enriched for several cancer cell stemness hallmarks and CsC pre-metastatic niche, which support these miRNAs role in suppression of HCsCs neoplastic transformation. Further, we constructed miRNA-transcription factor (tF) regulatory networks, which provided new insights on the role of the proposed miRNA-tF co-regulation in the cancer stemness axis and its cross talk with the surrounding microenvironment. our analysis revealed HCsC important hubs as candidate regulators for targeting hepatic cancer stemness such as, miR-148a, miR-214, E2F family, MYC and SLC7A5. Finally, we proposed a possible model for miRNA and TF co-regulation of HCSC signaling pathways. Our study identified an HCSC signature and set bridges between the reported results to give guide for future validation of HCC therapeutic strategies avoiding drug resistance. Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide 1. Accumulating evidence suggests the hepatic cancer stem cells (HCSC) to be the main organizer for the HCC initiation, as hepatic tumor initiating cells (HTIC). HCSC are a distinct subset of undifferentiated cells endowing tumorigenic and stem-like-characteristics. HCSCs could be identified by various cell surface markers including CD13, CD24, CD44, CD90, CD133, EpCAM (CD326) and OV6 2 , or by selection for the side population cells and those with a high aldehyde dehydrogenase activity 3. Stemness features of HCSCs include persistent self-renewal, colony and sphere forming abilities and sustained ability of proliferation and differentiation into a tumor bulk. HCSCs are also related to poor outcomes and recurrence in HCC patients, due to their potentials for migration, invasion, metastasis, epithelial-to-mesenchymal transition (EMT) and drug-resistance. Research over the past decade has unraveled that HCSC are regulated by many factors including HCSC niche, genetic and epigenetic microenvironment and stemness-related signaling pathways 2. These factors drive the CSC to exhibit metabolic flexibility 4 and promote angiogenesis 5 , neurogenesis 6 and immune resistance 7. Moreover, these factors confer the bio-energetic and biosynthetic requirements for maintenance of the tumor homeostasis and progression 2. Thus, the deeper
Open Access Macedonian Journal of Medical Sciences
BACKGROUND: Cell therapies offer a promising potential in promoting bone regeneration. Stem cell ... more BACKGROUND: Cell therapies offer a promising potential in promoting bone regeneration. Stem cell therapy presents attractive care modality in treating degenerative conditions or tissue injuries. The rationale behind this is both the expansion potential of stem cells into a large cell population size and its differentiation abilities into a wide variety of tissue types, when given the proper stimuli. A progenitor stem cell is a promising source of cell therapy in regenerative medicine and bone tissue engineering. AIM: This study aimed to compare the osteogenic differentiation and regenerative potentials of human mesenchymal stem cells derived from human bone marrow (hBM-MSCs) or amniotic fluid (hAF-MSCs), both in vitro and in vivo studies. SUBJECTS AND METHODS: Human MSCs, used in this study, were successfully isolated from two human sources; the bone marrow (BM) and amniotic fluid (AF) collected at the gestational ages of second or third trimesters. RESULTS: The stem cells derived f...
Stem Cell Reviews and Reports
EXCLI journal, 2017
Endometriosis is defined by presence of endometrial-like-tissue outside the uterus. Recently, ect... more Endometriosis is defined by presence of endometrial-like-tissue outside the uterus. Recently, ectopic endometriotic lesions have been suggested to originate by abnormal differentiation of endometrial mesenchymal stem cells (eMSCs). MicroRNAs (miRNAs) play an important role in the pathophysiology of endometriosis. Through a PCR array approach, we aimed to assess the differential expression of microRNAs in human eMSC treated in culture with sera derived from women with severe endometriosis. Sera were collected from five patients with severe endometriosis and three control women and added individually in the culture medium to conduct experimental and control eMSC sets, respectively. Regular microscopic follow-up for cell morphology was performed. SYBR Green based real-time PCR array was used to assess the expression of 84 miRNAs. Bioinformatics analysis was done to predict the target genes of the significantly dysregulated miRNAs and their enriched biological processes and pathways. Th...
Tumor Biology
Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular ... more Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks-linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein-protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.
Genomics, Proteomics & Bioinformatics, 2013
We aimed to shed new light on the roles of microRNAs (miRNAs) in liver cancer using an integrativ... more We aimed to shed new light on the roles of microRNAs (miRNAs) in liver cancer using an integrative in silico bioinformatics analysis. A new protocol for target prediction and functional analysis is presented and applied to the 26 highly differentially deregulated miRNAs in hepatocellular carcinoma. This framework comprises: (1) the overlap of prediction results by four out of five target prediction tools, including TargetScan, PicTar, miRanda, DIANA-microT and miRDB (combining machine-learning, alignment, interaction energy and statistical tests in order to minimize false positives), (2) evidence from previous microarray analysis on the expression of these targets, (3) gene ontology (GO) and pathway enrichment analysis of the miRNA targets and their pathways and (4) linking these results to oncogenesis and cancer hallmarks. This yielded new insights into the roles of miRNAs in cancer hallmarks. Here we presented several key targets and hundreds of new targets that are significantly enriched in many new cancer-related hallmarks. In addition, we also revealed some known and new oncogenic pathways for liver cancer. These included the famous MAPK, TGFb and cell cycle pathways. New insights were also provided into Wnt signaling, prostate cancer, axon guidance and oocyte meiosis pathways. These signaling and developmental pathways crosstalk to regulate stem cell transformation and implicate a role of miRNAs in hepatic stem cell deregulation and cancer development.
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Papers by Nourhan Abu Shahba