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result(s) for
"Megahed, Fayed"
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MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1
2021
Monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide from Entamoeba histolytica . Our previous study found that MLIF protects against ischemic stroke in rats and mice and exerts a neuroprotection effect in human neuroblastoma SH-SY5Y cells. Microglia/macrophage polarization has been proven to be vital in the pathology of ischemic stroke. Nevertheless, whether MLIF is able to modulate microglia/macrophage polarization remains unclear. We performed middle cerebral artery occlusion (MCAO) on C57BL/6J male mice and induced cultured BV2 microglia by oxygen-glucose deprivation (OGD), respectively. Immunfluorescence was utilized to detect the M1/2 markers, such as CD206 and CD16/32. qPCR and ELISA were used to detect the signature gene change of M1/2. The MAPK and NF-κB pathway associated proteins were measured by Western blot. To identify the protein target of MLIF, a pull-down assay was performed. We found that MLIF promoted microglia transferring from a “sick” M1 phenotype to a “healthy” M2 phenotype in vivo or in vitro . Furthermore, we proved that eukaryotic elongation factor 1A1 (eEF1A1) was involved in the modulation of microglia/macrophage polarization. Knocking down eEF1A1 by siRNA exhibited the M1 promotion effect and M2 inhibition effect. Taken together, our results demonstrated MLIF modulated microglia/macrophage polarization by targeting eEF1A1 in ischemic stroke.
Journal Article
NAIP Gene Deletion and SMN2 Copy Number as Molecular Tools in Predicting the Severity of Spinal Muscular Atrophy
by
Abd El Mutaleb, Abdel Nasser H.
,
Ibrahim, Fawziya A. R.
,
Omar, Tarek E. I.
in
Apoptosis
,
Atrophy
,
Biochemistry
2024
Spinal muscular atrophy (SMA) is one of the most prevalent autosomal recessive illnesses with type I being the most severe type. Genomic alterations including survival motor neuron (
SMN)
copy number as well as deletions in
SMN
and Neuronal Apoptosis Inhibitory Protein
(NAIP)
are greatly implicated in the emergence of SMA. However, the association of such alterations with the severity of the disease is yet to be investigated. This study was directed to elucidate the molecular assessment of
NAIP
and
SMN
genomic alterations as a useful tool in predicting the severity of SMA among patients. This study included 65 SMA pediatric patients (30 type I and 35 type II) and 65 healthy controls. RFLP-PCR was employed to determine the genetic polymorphisms of the
SMN1
,
SMN2
, and
NAIP
genes. In addition, qRT-PCR was used to identify the expression of the
SMN1
and
SMN
2 genes, and serum levels of creatine kinase were measured using a colorimetric method. DNA sequencing was performed on some samples to detect any single nucleotide polymorphisms in
SMN1, SMN2, and NAIP
genes. All SMA patients had a homozygous deficiency of
SMN1
exon 7. The homozygous deficiency of
SMN1
exons 7 and 8, with the deletion of
NAIP
exon 5 was found among the majority of Type I patients. In contrast, patients with the less severe condition (type II) had
SMN1
exons 7 and 8 deleted but did not have any deletions in
NAIP
, additionally; 65.7% of patients had multiple copies of
SMN2
. Analysis of
NAIP
deletion alongside assessing
SMN2
copy number might enhance the effectiveness of the diagnosis that can predict severity among Spinal Muscular Atrophy patients.
Journal Article
The Intrinsic Innate Immunity of Hepatocytes Suppresses HBV Replication and Is Antagonized by HBx
by
Liu, Qin
,
Zhou, Qi
,
Xie, Qingdong
in
Analysis
,
Bioinformatics
,
Carcinoma, Hepatocellular - immunology
2025
(1) Background: Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of viruses that interact with hepatocytes. HBV infection is a major global health problem. Most adults clear the infection quickly after being infected with HBV, while a few people develop chronic HBV infection. It is well-known that the early innate immune response of host cells plays an important role in the fight against virus infection. However, the interactions between HBV and the intrinsic innate immune system of hepatocytes are still not fully understood. The aim of this study was to confirm the interaction between HBV and hepatocytes, and to identify the interferon-stimulated genes (ISGs) regulated by HBx and their expression in association with HBV-associated HCC (HBV-HCC), so that we can refine our understanding of the interaction between HBV and ISGs and its potential influence on HBV-HCC. (2) Methods: We analyzed data concerning the stimulation of IFN-dependent genes in primary human hepatocytes (PHHs) transfected with pathogen DNA mimetics or infected with HBV in the GSE69590 database. Bioinformatic methods, such as GSEA, GO, and KEGG, were used to analyze the differentially expressed innate immunity genes and their related pathways to identify candidate intrinsic innate immune factors. qPCR on HepG2 and Huh7 cells, which highly express HBx, was used to detect relevant intrinsic innate immune factors. qPCR, RNAi, and Elisa methods were used to identify intrinsic innate immune factors in HBV-integrated HepG2.2.15 cells, and bioinformatics analysis was conducted on the HBV-infected tissues and cells in the GEO database. (3) Results: Inhibition of the JAK-STAT pathway enhanced HBV replication in HepG2 cells transfected with HBV plasmid and HepG2-NTCP cells infected with HBV. GSEA analysis of the GSE69590 data revealed significant changes in intrinsic innate immune pathways during HBV infection with PHH for 40 h. A total of 84 differentially expressed, candidate innate immunity genes were identified in GSE69590. Validation showed that
and
were down-regulated when HBx was expressed. Consistently,
and
were up-regulated following inhibition of HBx by transfection of HBx siRNA into HepG2.2.15 cells, and HBV pgRNA was up-regulated following down-regulated expression of
and
in HEK293 cells. Receiver operating characteristics (ROC) and overall survival (OS) analysis of 204 HBV-HCC patients showed that expression of
was closely associated with HBV-HCC, and high expression of
was associated with longer survival. (4) Conclusions: Innate immunity genes
and
are regulated by HBx, and higher expression of
is closely related to longer survival of HBV-HCC patients.
Journal Article
The association between body mass index elevation and differentiation in vitamin D receptor gene expression, genetic polymorphism, and oxidative stress in adult Egyptian individuals
by
Shaban, Nadia Z.
,
Atta, Mohamed N.
,
Abdul-Aziz, Ahmed A.
in
25-Hydroxyvitamin D
,
631/208
,
631/337
2023
Vitamin D plays a central role in maintaining calcium, phosphorus, and bone homeostasis in close interaction with the parathyroid hormone. Obesity is a significant health problem worldwide, particularly in developed nations. The current study was carried out to investigate the possible relationship between body mass index (BMI) elevation and differentiation in 25-hydroxyvitamin D (VD), vitamin D receptor (VDR) gene expression, and genetic polymorphism besides oxidative stress in adult Egyptian individuals. This was done to explore the mechanisms underlying the suggested role of the VD/VDR complex in the pathogenesis of obesity. A total of 70 subjects (30 obese, 25 overweight, and 15 normal, age: 20–50 years, without other chronic diseases) were selected. The study focused on the determination of VD, VDR gene polymorphism, VDR gene expression, alkaline phosphatase, calcium, phosphorus, glucose, lipid profile, oxidative stress including, oxidant (malondialdehyde), and anti-oxidants (reduced glutathione and superoxide dismutase). The results showed that elevation in BMI led to the percentage of the Ff 'allele' becoming predominant, while the percentage of the FF 'allele' was in the normal BMI range. Also, BMI elevation caused significant reductions in VD and VDR expression, with significant elevations in alkaline phosphatase and the levels of calcium and phosphate in serum. Also, oxidative stress increases with increasing BMI. Elevation in BMI causes a reduction in VD concentration and VDR gene expression levels. Also, the percentage of heterozygous mutant genotype Ff 'allele' is predominantly in the obese human, in contrast to normal subjects, where the percentage of homozygous wild genotype FF 'allele' is predominant. In general, the genetic expression and polymorphism of VD and VDR can be used as a genetic marker for predisposition, diagnosis, prognosis, and progression of obesity.
Journal Article
Quantum Dot Nanomaterials: Preparation, Characterization, Advanced Bio-Imaging and Therapeutic Applications
2024
The bio-imaging technology is one of the most significant modern applications used in several fields, including early diagnosis of many illnesses that are most important diseases facing humanity and other vital uses. The primary advancement in nanotechnology is the creation of innovative fluorescence probes called quantum dots (QDs). The use of molecular tagging in research, in vivo, and in vitro studies is revolutionized by quantum dots. The application of QD indicates conversion in natural imaging and photography has demonstrated extraordinary appropriateness in bio-imaging, the discovery of novel drugs, and delivery of targeted genes, biosensing, photodynamic therapy, and diagnosis. New potential methods of early cancer detection and treatment management are being researched as a result of the special physical and chemical characteristics of QD probes. The bio-imaging technique depends on the fluorescent emission of the used materials, which is paired with living cells that are easy to see it in 3D without any surgical intervention. Therefore, the use of QDs many types that have unique and appropriate properties for use in that application; In terms of fluorescent emission strength, duration and luminosity.This review article displays some methods of preparation for QDs nanomaterials and the devices used in this. In addition, it presentssome of challenges that must be avoided for the possibility of using them in the bio-imaging field; as toxicity, bio-compatibility, and hydrophilization. It’s reviewed some of the devices that use QDs in bio-imaging technique, the QDs application in cell analysis-imaging, and QDs application in vivo imaging.
Journal Article
The Interactions Between HBV and the Innate Immunity of Hepatocytes
by
Megahed, Fayed Attia Koutb
,
Zhou, Xiaoling
,
Sun, Pingnan
in
adults
,
Cell Line
,
Cells, Cultured
2020
Hepatitis B virus (HBV) infection affects ~350 million people and poses a major public health problem worldwide. HBV is a major cause of cirrhosis and hepatocellular carcinoma. Fewer than 5% of HBV-infected adults (but up to 90% of HBV-infected infants and children) develop chronic HBV infection as indicated by continued, detectable expression of hepatitis B surface antigen (HBsAg) for at least 6 months after the initial infection. Increasing evidence indicates that HBV interacts with innate immunity signaling pathways of hepatocytes to suppress innate immunity. However, it is still not clear how HBV avoids monitoring by the innate immunity of hepatocytes and whether the innate immunity of hepatocytes can be effective against HBV if re-triggered. Moreover, a deep understanding of virus–host interactions is important in developing new therapeutic strategies for the treatment of HBV infection. In this review, we summarize the current knowledge regarding how HBV represses innate immune recognition, as well as recent progress with respect to in vitro models for studying HBV infection and innate immunity.
Journal Article
MicroRNAs: Small Molecules with Significant Functions, Particularly in the Context of Viral Hepatitis B and C Infection
by
Petrovic, Ana
,
Smolic, Martina
,
Atta, Shimaa
in
Antiviral drugs
,
Biomarkers
,
Biomarkers - metabolism
2023
A MicroRNA (miRNA) is defined as a small molecule of non-coding RNA (ncRNA). Its molecular size is about 20 nucleotides (nt), and it acts on gene expression’s regulation at the post-transcription level through binding to the 3’untranslated regions (UTR), coding sequences, or 5’UTR of the target messenger RNAs (mRNAs), which leads to the suppression or degradation of the mRNA. In recent years, a huge evolution has identified the origin and function of miRNAs, focusing on their important effects in research and clinical applications. For example, microRNAs are key players in HCV infection and have important host cellular factors required for HCV replication and cell growth. Altered expression of miRNAs affects the pathogenicity associated with HCV infection through regulating different signaling pathways that control HCV/immunity interactions, proliferation, and cell death. On the other hand, circulating miRNAs can be used as novel biomarkers and diagnostic tools for HCV pathogenesis and early therapeutic response. Moreover, microRNAs (miRNA) have been involved in hepatitis B virus (HBV) gene expression and advanced antiviral discovery. They regulate HBV/HCV replication and pathogenesis with different pathways involving facilitation, inhibition, activation of the immune system (innate and adaptive), and epigenetic modifications. In this short review, we will discuss how microRNAs can be used as prognostic, diagnostic, and therapeutic tools, especially for chronic hepatitis viruses (HBV and HCV), as well as how they could be used as new biomarkers during infection and advanced treatment.
Journal Article
Evaluation of Anti-Diabetic and Sensory Effect of Fermented Rayeb Milk Fortified with Nano-Lemon Grass in Male Rats
by
Abdel-Kader, Mariam Ahmed Ali
,
Megahed, Fayed Attia Koutb
,
Elwardany, Neveen A
in
اللبن الرائب
,
عشبة الليمون
,
مرضى السكري
2024
Lemongrass (Cymbopogon citratus DC, Stapf.), a member of family Poaceae, is commonly used to cure several diseases. Lemongrass aqueous extract (LGE) and LGE-loaded chitosan nanoparticles (LGECSNPs) exhibited potential effectiveness as antioxidant, anti-diabetic, and protective effects in male rats. Reducing power, free radical scavengers and Haemolytic activity of LGE and LGE-CSNPs were evaluated on protein levels. Total phenolics and total flavonoid contents were studied using (HPLC). Six groups of thirty-six adult male albino rats were given three different measurements of C. citratus LGE-CSNPs orally. Antioxidant activities and oxidative stress of LGE-CSNPs were evaluated on protein levels. Diabetic parameter (HBA1C) was determined. Pancreatic histopathological examinations were also studied. The sensory properties of this blind as a food supplement to fermented milk (Rayeb milk) were also evaluated. The polyphenol fingerprint of LGE revealed that chlorogenic acid (14.56 mg/ml), and quercetin (18.25 mg/ml) were the major polyphenols present in this extract. Glutathione peroxidase (GPx) of LGE-CSNPs as antioxidant activity was more active than LGE. Thiobarbituric Acid Reactive Substance (TABRAS) as oxidant concentrations and free radical scavengers have been decreased in the reference drug (Metformin), LGE, and LGE-CSNPs-treated rat groups compared to the control group (untreated). LGE-CSNPs (5 mg/kg Bwt) exhibited the lowest levels of TABRAS and (GPx). Diabetes parameters have been decreased in LGE-CSNPs (5 mg/kg Bwt) (5.13) in comparison with the reference drug (5.62). Results suggested a natural nutritional supplement that improves diabetics' condition of health. It is recommended to be added to fermented milk (Rayeb milk) as a nutritional supplement.
Journal Article
Anti-Hyperlipidemia Protective Effect of Helianthus Tuberosus Extract in Male Rats and Evaluation of its Sensory Effect on Chicken and Shrimp Pop
by
Abdel-Kader, Mariam Ahmed Ali
,
Megahed, Fayed Attia Koutb
,
Elwardany, Neveen A
in
درنات الطرطوفة
,
ذكور الجرذان
,
كرات الدجاج
2024
This study aimed to reach a comprehensive biological evaluation of Jerusalem artichoke (Helianthus tuberoses L.) tubers aqueous extract in adult male albino and to determine its influence on anti-hyperlipidemia protective and sensory properties of chicken and shrimp pops fortified with the extract. Thirty-six adult male albino rats were divided into six groups and treated orally with three concentrations (100, 200, and 300 mg/kg body weight) of H. tuberoses extract. Blood and liver samples were collected to measure the biochemical indicators, protein level, antioxidant parameters, and histopathological examination. Chicken and shrimp pops fortified with the extract were evaluated for their sensory characteristics. The results showed that decrease in liver and adipose tissue weights using H. tuberoses extract as compared with reference drug (Atorvastatin) group, especially at H. tuberoses extract (200mg/kg bwt). Liver aminotransferase enzyme activity (AST and ALT) significantly increased in the control positive group compared to the control negative group. H. tuberosus extract-treated groups. Total count of HB, other blood indices, and platelets count were slightly increased in treated groups with extract as compared with the reference drug (Atorvastatin) group. Antioxidant enzymes activities (GPx and SOD) were observed at the highest activities were observed at H. tuberosus extract 100, 300 mg/kg bwt. Administration of the extract induced a significant improvement in histological picture of the liver. Sensory evaluation of chicken and shrimp pops fortified with extract showed acceptability related to taste, tenderness, and appearance. H. tuberoses extract could be used as antihyperlipidemic, properties when used as a food supplement
Journal Article
The interplay between non-alcoholic fatty liver disease and innate immunity in hepatitis B virus patients
by
Megahed, Fayed Attia Koutb
,
Elmaghrabi, Marwa Mohamed
,
Zhou, Xiaoling
in
Analysis
,
Body mass index
,
Care and treatment
2021
Non-alcoholic fatty liver disease (NAFLD) is the most epidemic liver disorder worldwide as a result of rapid lifestyle transformation over the past few decades and is expected to elevate in the next few years as well as it is ranging from plain hepatic steatosis via non-alcoholic steatohepatitis (NASH) to liver cirrhosis and hepatocellular carcinoma (HCC). The liver is an essential innate immune organ with large numbers of innate immune cells that contribute in NAFLD pathogenesis, additionally play the influential role that control NAFLD progression in the hepatitis B patients. Here, we summarized the recent advances in understanding and managing the NAFLD patients with chronic hepatitis B infection and interplay with innate immunity.
Journal Article