Hani Hafez
Suez Canal University, Biology, Faculty Member
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The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its further use in cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted... more
The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its further use in cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted O-carboxymethyl chitosan (GA@CMCS) against nephrotoxicity induced by CDDP in rats. Renal injury was assessed in the GA@CMCS/CDDP-treated rats using kidney injury molecule-1 (KIM-1). Moreover, the levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were measured. The comet assay was performed to measure the DNA damage. The renoprotective activity of GA@CMCS was supported by histo- and immuno-pathological studies of the kidney. GA@CMCS significantly normalized the increases in kidney homogenate of KIM-1, MDA, and NO-induced by CDDP and significantly increased GSH as compared with the CDDP group. GA@CMCS also significantly protects rat kidneys from CDDP-induced histo- and immuno-pathological changes. Both biochemical findi...
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AIM The current study aimed to explore the pretreatment of bone marrow mesenchymal stem cells (BMSCs) with hyaluronic acid (HA) on renal fibrosis in Adriamycin- induced CKD in rats. MATERIAL AND METHODS Sixty male SD rats were alienated... more
AIM The current study aimed to explore the pretreatment of bone marrow mesenchymal stem cells (BMSCs) with hyaluronic acid (HA) on renal fibrosis in Adriamycin- induced CKD in rats. MATERIAL AND METHODS Sixty male SD rats were alienated into 4 equal groups; The control group: rats received two saline injections at 1 and 14 days, adriamycin (ADR) group: rats were injected i.v. twice via tail vein at day one and after 2 weeks, BMSCs group; rats were injected i.v. twice after 5 days of each ADR injection, and HA + BMSCs; rats were i.v. injected twice with BMSCs pretreated with 1 mg/ml HA after 5 days of each ADR injection. Protective role of BMSCs on renal function and morphology was detected using biochemical analysis, molecular studies, histopathological, and immunohistohemical investigations. RESULTS Pretreatment of BMSCs with HA showed significant decrease in KIM-1, and increase in serum albumin compared to CKD group (p < 0.05). Moreover, it reduced the expression of the apoptotic marker Caspase-3, the inflammatory markers TNF and IL-6, and the fibrotic markers Wnt7a, β-catenin, and fibronectin1 than the CKD group (p < 0.05). CONCLUSION The current outcomes suggested that BMSCs preconditioned with HA could attenuate the renal fibrosis in adriamycin- induced CKD.
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Research Interests: Neuroscience, Stem Cells, Biology, Stem Cell, Medicine, and 15 moreNeurodegenerative Diseases, Stem Cell Transplantation, Amyotrophic Lateral Sclerosis, Biological Sciences, Neural stem cell, Humans, Old Age, Animals, Disease, Embryonic Stem Cell, Animal Model, Mesenchymal Stem Cell, Neurodegenerative Disease, Alzheimer Disease, and Parkinson Disease
The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its futher use for cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted... more
The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its futher use for cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted O-carboxymethyl chitosan (GA@CMLMWC) against nephrotoxicity induced by CDDP in rats. Renal injury was assessed in the GA@CMLMWC/CDDP-treated rats using kidney injury molecule-1 (KIM-1). Moreover, the levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were measured. The comet assay was performed to measure the DNA damage. The renoprotective activity of GA@CMLMWC was supported by histo- and immuno-pathological studies of the kidney. GA@CMLMWC significantly normalized the increases in kidney homogenate of KIM-1, MDA, and NO-induced by CDDP and significantly increased GSH as compared with the CDDP group. GA@CMLMWC also significantly protects rat kidneys from CDDP-induced histo- and immuno-pathological changes. Both biochem...
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Background: Nonalcoholic steatohepatitis (NASH) is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. A high fat high cholesterol diet (HFD) was provided to female albino rats to... more
Background: Nonalcoholic steatohepatitis (NASH) is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. A high fat high cholesterol diet (HFD) was provided to female albino rats to establish a NASH model. It is well known that the offspring of obese mothers have an increased risk of obesity and diabetes. The present study aimed at evaluating the ameliorative effects of ipriflavone (IP) as a natural food supplement on lipid metabolism, improving insulin sensitivity, reducing oxidative stress and inflammation, modifying metabolic risk factors and/or reduce brain damage, in both neonates and their dams. Materials and Methods: The present aim was achieved by evaluating the oxidative stress and antioxidant defense system biomarkers, as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) activities. In addition, the neurotransmitter acetylcholine (Ach) and acetylcho...
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Background: Nephrotoxicity is considered one of the most serious and dose-limiting factors for restricting clinical use of Cisplatin and anticancer efficacy. Gallic acid is a non-toxic substance that has a wide range of therapeutic roles... more
Background: Nephrotoxicity is considered one of the most serious and dose-limiting factors for restricting clinical use of Cisplatin and anticancer efficacy. Gallic acid is a non-toxic substance that has a wide range of therapeutic roles with high antioxidant activity. So, the present study aims to investigate the concurrent protective action of Gallic acid against inflammatory and oxidative damage caused by Cisplatin in rat kidneys. Material and methods: Thirty-two male albino rats were classified into four groups, eight per each as follows: Group 1 (Normal Control group): without treatment. Group 2 (Gallic acid group): healthy rats were given Gallic acid. Group 3 (Cisplatin group): healthy rats were injected with cisplatin. Group 4 (Gallic acid + Cisplatin) treated group. Kidney functions, Paraoxonase-1, and inflammatory cytokines such as Tumor Necrosis Factor α, respectively were determined. Results: Cisplatin was induced kidney damage with a high significance (P <0.001) regar...
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Insulin resistance induces nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). W e used a high-fat, high-calorie solid diet (HFD) to create a model of insulin resistance and NASH in nongenetically modified rats and... more
Insulin resistance induces nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). W e used a high-fat, high-calorie solid diet (HFD) to create a model of insulin resistance and NASH in nongenetically modified rats and to stu dy the relationship between visceral adipose tissue and liver. Obesity and insulin resis tance occurred in HFD rats, accompanied by a marked reduction in visceral adipose tissue adiponectin-mRNA and deterioration of lipid profile . These modifications lead to hepatic steatosis acc ompanied by oxidative stress phenomena, necroinflammation, and hepatocyteballoon ing .Oral administration of ipriflavone (IP), to HF D-treated animals restored adipose tissue adiponectin expression, highly effective in decreasing the levels of serum total cholesterol (T C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), alanine aminotrans ferase (ALT) and aspartate aminotransferase (AST). It could decrease lipid accumulation in the hepatocytes and a...
Long-term exposure to environmental neurotoxic metals is implicated in the induction of dementia and cognitive decline. The present study aims to illustrate the therapeutic role of ipriflavone as a synthetic isoflavone against... more
Long-term exposure to environmental neurotoxic metals is implicated in the induction of dementia and cognitive decline. The present study aims to illustrate the therapeutic role of ipriflavone as a synthetic isoflavone against environmental metal–induced cognitive impairment in rats. Dementia was induced by a mixture of aluminum, cadmium, and fluoride for 90 days followed by ipriflavone for a further 30 days. Metal-treated animals exhibited abnormal behaviors in the Morris water maze task. Neuropathological biomarkers including oxidative stress (TBARS, NO, SOD, GPX, GST, and GSH), inflammation (TNF- α, IL-6, and IL-1β), neurotransmission (AChE and MAO), and insulin resistance (insulin, insulin receptor, and insulin-degrading enzyme) were altered, which consequently elevated the level of amyloid-β42 and tau protein in the hippocampus tissues inducing neuronal injury. Ipriflavone significantly (P < 0.05) ameliorated the neurobehavioral abnormalities and the cognitive dysfunction biomarkers via antioxidant/anti-inflammatory mechanism. Moreover, ipriflavone downregulated the mRNA expression level of amyloid precursor protein and tau protein, preventing amyloid plaques and neurofibrillary tangle aggregation at P < 0.05. A molecular docking study revealed that ipriflavone has a potent binding affinity towards AChE more than donepezil and acts as a strong AChE inhibitor. Our data concluded that the therapeutic potential of ipriflavone against dementia could provide a new strategy in AD treatment.
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A novel anticancer and anti-inflammatory agent based on hybrid curcuminoid-Gboxin analog (FLLL49-GbA) and its macromolecular silver(I) complex (Ag(I)FLLL49-GbA) have successfully synthesized. In addition, chitosan nanoparticles (CNPs)... more
A novel anticancer and anti-inflammatory agent based on hybrid curcuminoid-Gboxin analog (FLLL49-GbA) and its macromolecular silver(I) complex (Ag(I)FLLL49-GbA) have successfully synthesized. In addition, chitosan nanoparticles (CNPs) were used to encapsulate this macromolecular complex, targeting enhancing its therapeutic effect and minimizing its side impacts. The encapsulated Ag(I) complex was significantly triggered apoptosis (P < 0.05) with much more rapidly release of Ag(I)FLLL49-GbA from the CNPs at pH 5.3 than at pH 7.4, which is beneficial for cancer-targeted drug delivery. Free complex showed promising ability in preventing glucose uptake and lactate production coupled with cellular ATP depletion in cancer cells. Additionally, there was significant decrease in the inflammatory cytokines in breast cancer (MCF-7) and lung cancer (A549) cells with values of P < 0.01 and P < 0.001 after 24 h incubation. Furthermore, the death-inducing proteins have been significantly up-regulated (P < 0.01 to P < 0.001) after 36 h incubation of cancer cells. Consequently, the novel curcuminoid macromolecule showed significant feasibility in triggering the high expression of apoptotic caspases caspase 3, caspase 8, P53, and Bax (P < 0.01 to P < 0.001) after 48 h of chemotherapy. Noteworthy, the cytotoxicity of Ag(I)FLLL49-GbA was significantly increased toward cancer cells (MCF-7 > A549), while, reduced toward normal cells (HeLa) after loading on chitosan Nano-vehicles.
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In this work, we have successfully upgraded the crab wastes into Pd(II) complex of Gboxin analog–chitooligosaccharides conjugate (Pd(II)COS@GbA). This new complex has a high capacity to inhibit the proliferation of prostate cancer cells... more
In this work, we have successfully upgraded the crab wastes into Pd(II) complex of Gboxin analog–chitooligosaccharides conjugate (Pd(II)COS@GbA). This new complex has a high capacity to inhibit the proliferation of prostate cancer cells (IC50 = 1.92 μg/ml). This activity could be attributed to its ability to induce mitochondrial fragmentation through increasing mitochondrial fission dynamin‐related protein 1 (p < .05) and down‐regulation of optic atrophy 1 proteins (p < .05). Moreover, this complex can effectively disrupt ATP synthase action leading to declined ATP production, along with downstream of ATPase inhibitor factor1 that hinder energy production in the cancer cells. Also, it has an anti‐inflammatory effect by triggering modulators for the release of inflammatory molecules such as TNF‐α (p < .05), IL‐6 (p < .05), and mRNA transcripts of COX‐II (p < .01). Therefore, Pd(II)COS@GbA exhibited significant anti‐prostate cancer activity through different mechanisms in inducing energy depletion and mitochondrial fragmentation leading to disrupted oxidative phosphorylation (OXPHOS). Complex Pd(II)COS@GbA is more cytotoxic for PC3 than RWPE‐1 which in turn means it is may act as a selective cytotoxic agent for prostate cancer.
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Background: Epithelial-mesenchymal transition (EMT) is a critical event in wound healing and tissue repair following injury. Transforming growth factor beta-1 (TGFβ1) plays an important role in inducing EMT in lung epithelial cells in... more
Background: Epithelial-mesenchymal transition (EMT) is a critical event in wound healing and tissue repair following injury. Transforming growth factor beta-1 (TGFβ1) plays an important role in inducing EMT in lung epithelial cells in vitro and in vivo. As fibroblast growth factor-2 (FGF2) reverses TGFβ1-induced collagen I (COL1A1) and α-smooth muscle actin (Actin alpha 2; ACTA2) expression in primary mouse and human lung fibroblasts, we set out this study to determine the effect of FGF2 on TGFβ1-induced EMT in human lung epithelial cells. Methods: BEAS-2B and A549 cells were treated with recombinant FGF2 (2 nM) with or without TGFβ1 (2 ng/ml) for up to 4 days. The phenotypic alterations associated with EMT were assessed by quantitative real-time PCR and E-cadherin protein expression levels was assayed by western blot and immunofluorescence staining. Cell migration was confirmed using wound-healing assay. Results: TGFβ1 treatment led to significantly reduced expression of E-cadherin...
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Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or... more
Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin-induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double-transgenic (DTG) mice with doxycycline-inducible overexpression of human FGF2 (SPC-rtTA;TRE-hFGF2) or single-transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild-type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline-induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 ...
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Heavy metals are reported as neurodegenerative disorders progenitor. They play a role in the precipitation of abnormal β-amyloid protein and hyper-phosphorylated tau, the main hallmarks of Alzheimer's disease (AD). The present study... more
Heavy metals are reported as neurodegenerative disorders progenitor. They play a role in the precipitation of abnormal β-amyloid protein and hyper-phosphorylated tau, the main hallmarks of Alzheimer's disease (AD). The present study aimed to validate the heavy metals-induced Alzheimer's-like disease in rats as an experimental model of AD and explore the therapeutic effect of berberine via tracking its effect on the oxidative stress-inflammatory pathway. Alzheimer's-like disease was induced in rats orally by a mixture of aluminium, cadmium and fluoride for three months, followed by berberine treatment for another one month. Berberine improved the cognitive behaviors in Morris water maze test and offered a protective effect against heavy metals-induced memory impairment. Docking results showed that berberine inhibited acetylcholineesterase, COX-2 and TACE. Matching with in silico study, berberine downregulated the AChE expression and inhibited its activity in the brain tis...
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Research Interests: Psychopharmacology, Oxidative Stress, Medicine, Hippocampus, Blood brain barrier, and 14 moreAnimals, Male, Mitogen Activated Protein Kinase, Rats, Wistar Rats, Memory Disorders, Scopolamine, Memory Impairment, Neuroprotective Agents, Brain-derived neurotrophic factor (BDNF), isoflavones, Psychology and Cognitive Sciences, Medical and Health Sciences, and Scopolamine hydrobromide
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The human cytochrome P4501A1 (CYP1A1) enzyme plays an important role in the metabolism of xenobiotics and endogenous substrates. Because polymorphisms within the CYP1A1 gene have been shown to be associated with various cancer risks and... more
The human cytochrome P4501A1 (CYP1A1) enzyme plays an important role in the metabolism of xenobiotics and endogenous substrates. Because polymorphisms within the CYP1A1 gene have been shown to be associated with various cancer risks and with the predicting clinical efficacy of some chemotherapies in different populations , most studies focus on their clinical significance. We, however, were interested in evaluating whether the polymorphisms could be used to distinguish human populations. Four single nucleotide CYP1A1 polymorphisms (rs4646903/ g.75011641; rs1048943/g.75012985; g.75012235; and rs1799814/ g.75012987) were analyzed via PCR-RFLP assay in 1,195 individuals of various human groups from all over the world. In order to gain a more complete view of the genetic variability of the CYP1A1 gene, different statistical analyses were performed upon the populations of the present study and upon the limited data gleaned from previously studied populations.The allele and haplotype fr...
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Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired... more
Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL). The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE) and amyloid beta precursor protein (AβPP). These changes were significantly correlated with decreased insulin degrading enzyme (IDE) and beta-amyloid40 (Aβ 40) and increased beta-amyloid42 (Aβ 42) in the hippocampal region. Daily administration of berberine (50 mg/kg) for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.
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We investigated the genetic diversity and population structure of Bufo arabicus (Duttaphrynus arabicus)from the Arabian Peninsula in Saudi Arabia, according to mitochondrial DNA (D-Loop). Samples were collected from toes and prepared for... more
We investigated the genetic diversity and population structure of Bufo arabicus (Duttaphrynus arabicus)from the Arabian Peninsula in Saudi Arabia, according to mitochondrial DNA (D-Loop). Samples were collected from toes and prepared for mitochondrial DNA extraction and Polymerase chain reaction using the suitable primers. The products were sequenced using ABI Prism Big-dye. Phylogenetic analysis was carried out using DnaSP. V.5 version and maximum likelihood tree were constructed using MEGA 6. There were high polymorphic sites among the two species with high diversity of haplotypes. Nucleotide diversity of Bufo arabicus from Abha region was the highest population. Tajima‟s D test showed significant results from neutrality for all Bufo arabicus populations with P˂ 0.05. Fu‟s Fs was positive for the whole population and positive for the separated regional populations supported the allele deficiency due to recent population bottleneck or over-dominant selection without gene flow resul...
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Major characteristics of AD are synaptic loss, cholinergic dysfunction, and abnormal protein depositions in the brain. The amyloid β peptide (Aβ), a proteolytic fragment of amyloid-β-precursor protein (APP), aggregates to form neuritic... more
Major characteristics of AD are synaptic loss, cholinergic dysfunction, and abnormal protein depositions in the brain. The amyloid β peptide (Aβ), a proteolytic fragment of amyloid-β-precursor protein (APP), aggregates to form neuritic plaques and has a causative role in AD. A present focus of AD research is to develop a new safe AChE inhibitor acting as Aβ lowering drugs. This work was aimed to study the effect and understand the mechanism by which berberine treated AD induced in animal model. AD induced in rats by oral administration of 5 ml of contaminant water with Fluroid, Nicotine, Al and cadmium at dose of (500ug/L-27.7uM, 5mg/L-0.03mM, 50mg/L-1.9mM and 25ug/L--0.22uM in water, respectively) for 3 months. Then the treatment with berberine at dose of 50 mg/kg was carried out for another one month. Firstly, we examined the berberine in silico and we found that berberine is potent anti-acetylcholine, down regulated TNF-α-converting enzyme and COX-2. Our biochemical and molecular...
Objectives: Study the link between insulin resistance and Alzheimer's disease pathogenesis and the activity of ipriflavone as a therapeutic agent on AD as a cholinesterase inhibitor. Methods: Alzheimer's disease induced in rats by... more
Objectives: Study the link between insulin resistance and Alzheimer's disease pathogenesis and the activity of ipriflavone as a therapeutic agent on AD as a cholinesterase inhibitor. Methods: Alzheimer's disease induced in rats by oral administration of 5 ml of contaminated water with fluoride, aluminum and cadmium at a dose of (500ug/L, 50mg/L, and 25ug/L, respectively) for 3 months followed by Ipriflavone supplemental dose of 50 mg/kg for an extra month. Experimental parameters measured before and after supplementation. The Dock Module of MOE with Monte Carlo process used for docking the Ipriflavone into the active site of the AChE. Results: Data revealed the increased HOMA-IR, decreased HOMA-β percentage, and decreased β-amyloid40 accompanied with increased AChE in the hippocampus region of rat's brain in our AD model. mRNA expression of amyloid precursor protein (APP) was up regulated with the increase of mRNA of AChE expression and insulin receptor and quantitative ...
The most abundant of the collagen protein family, type I collagen is encoded by the COL1A2 gene. The COL1A2 restriction fragment length polymorphisms (RFLPs) EcoRI, RsaI and MspI in samples from several different central-eastern... more
The most abundant of the collagen protein family, type I collagen is encoded by the COL1A2 gene. The COL1A2 restriction fragment length polymorphisms (RFLPs) EcoRI, RsaI and MspI in samples from several different central-eastern Mediterranean populations were analysed and found to be potentially informative anthropogenetic markers. The objective was to define the genetic variability of COL1A2 in the central-eastern Mediterranean and to shed light on its genetic distribution in human groups over a wide geographic area. PCR-RFLP analysis of EcoRI, RsaI and MspI polymorphisms of the COL1A2 gene was performed on oral swab and blood samples from 308 individuals from the central-eastern Mediterranean Basin. The genetic similarities among these groups and other populations described in the literature were investigated through correspondence analysis. Single-marker data and haplotype frequencies seemed to suggest a genetic homogeneity within the European populations, whereas a certain degree of differentiation was noted for the Egyptians and the Turks. The genetic variability in the central-eastern Mediterranean area is probably a result of the geographical barrier of the Mediterranean Sea, which separated European and African populations over time.