Publications by authors named "Attalla F El-Kott"

16 Publications

  • Page 1 of 1

Cadmium chloride induces non-alcoholic fatty liver disease in rats by stimulating miR-34a/SIRT1/FXR/p53 axis.

Sci Total Environ 2021 Aug 18;784:147182. Epub 2021 Apr 18.

Mansoura Research Centre for Cord Stem Cell (MARC-CSC), Stem cells bank, Children's Hospital, Mansoura University, Mansoura, Egypt.

Cadmium (Cd) is associated with non-alcoholic fatty liver disease (NAFLD). The hepatic activation of p53/miR-43a-induced suppression of SIRT1/FXR axis plays a significant role in the development of NAFLD. In this study, we have investigated CdCl-induced NAFLD in rats involves activation of miR34a/SIRT1/FXR axis. Adult male rats were divided into 4 groups (n-8/each) as a control, CdCl (10 mg/l), CdCl + miR-34a antagomir (inhibitor), and CdCl + SRT1720 (a SIRT1 activator) for 8 weeks, daily. With no effect on fasting glucose and insulin levels, CdCl significantly reduced rats' final body, fat pads, and liver weights, and food intake. Concomitantly, it increased the circulatory levels of liver markers (ALT, AST, and γ-GTT), increased the serum and hepatic levels of total cholesterol and triglycerides coincided with increased hepatic lipid accumulation. Besides, it increased the mRNA and protein levels of SREBP1, SREBP2, FAS, and HMGCOA reductase but reduced mRNA levels of PPARα, CPT1, and CPT2. Interestingly, CdCl also increased mRNA levels of miR34 without altering mRNA levels of SIRT1 but with a significant reduction in protein levels of SIRT1. These effects were associated with increased total protein levels of p53 and acetylated protein of p53, and FXR. Of note, suppressing miR-34a with a specific anatomic or activating SIRT1 by SRT1720 completely prevented all these effects and reduced hepatic fat accumulations in the livers of rats. In conclusion, CdCl induced NAFLD by increasing the transcription of miR-34a which in turn downregulates SIRT1 at the translational level.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147182DOI Listing
August 2021

Immunomodulatory effects of bee pollen on doxorubicin-induced bone marrow/spleen immunosuppression in rat.

J Food Biochem 2021 Jun 5;45(6):e13747. Epub 2021 May 5.

Zoology Department, College of Science, Fayoum University, Fayoum, Egypt.

This study investigated the immunomodulatory effects of Bee Pollen (BP) on Doxorubicin (DOX)-induced bone marrow/spleen suppression in rats. 48 Wistar rats were divided into 6 groups (n = 8/group); control, DOX (5 mg/kg), BP (100 mg/kg), BP (200 mg/kg), BP (100 mg/kg) +DOX, and BP (200 mg/kg) +DOX groups. BP was administered orally for 42 days and 5 mg/kg of DOX was injected intravenously at days 7, 14, 21, 28, 35 and 42. Hematological parameters, antioxidant enzymes and inflammatory cytokines were measured. Apoptosis-related genes were investigated using Real-Time PCR and western blot. DOX significantly decreased blood cells count, cytokines, and antioxidant enzyme. It also increased the expression of apoptotic genes in spleen and BM. The BP significantly improved hematopoietic function, antioxidant parameters, and serum levels of hematopoietic simulating-cytokines. Also, BP significantly reduced the expression of apoptotic genes. These results confirm the immunomodulatory activity of BP in DOX-induced biochemical, molecular and histological immunosuppression. PRACTICAL APPLICATIONS: Chemotherapy drugs are being developed every day but are limited due to their side effects. The most important side effect of chemotherapy drugs is the suppression of hematopoiesis through its direct effect on bone marrow and hematopoietic cells. Today, many studies are done on natural, synthetic and semi-synthetic compounds to reduce the effects of chemotherapy drugs. Compounds that, along with chemotherapy drugs in the treatment of various tumors, maintain the hematopoietic pathway, synergize the antitumor effects of chemotherapy drugs, and also protect other organs of the body from free radical damage produced by chemotherapy drugs. One of these natural compounds is bee pollen, which has all the properties mentioned in chemotherapy supplements and can be used in the pharmaceutical industry.
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http://dx.doi.org/10.1111/jfbc.13747DOI Listing
June 2021

A Novel Combination Therapy Using Rosuvastatin and Combats Dextran Sodium Sulfate-Induced Colitis in High-Fat Diet-Fed Rats by Targeting the TXNIP/NLRP3 Interaction and Influencing Gut Microbiome Composition.

Pharmaceuticals (Basel) 2021 Apr 8;14(4). Epub 2021 Apr 8.

Department of Microbiology and Biotechnology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt.

Inflammasome targeting and controlling dysbiosis are promising therapeutic approaches to control ulcerative colitis. This report is the first to investigate the mechanisms underlying the coloprotective effects of rosuvastatin and and their combined therapy on dextran sodium sulfate (DSS)-induced colitis in high-fat diet (HFD)-fed rats. Our results demonstrate the aggravation of intestinal inflammation as a consequence of an HFD following DSS administration. An association between dyslipidemia, LDL oxidation, CD36 expression, ROS generation, thioredoxin-interacting protein (TXNIP) upregulation, and NLRP3 inflammasome activation was demonstrated by DSS exposure in HFD-fed rats. We demonstrated that rosuvastatin/ significantly suppressed the DSS/HFD-induced increase in colon weight/length ratio, DAI, MDI, and myeloperoxidase, as well as corrected dysbiosis and improved histological characteristics. Additionally, caspase-1 activity and IL-1β-driven pyroptotic activity was significantly reduced. Rosuvastatin/ showed prominent anti-inflammatory effects as revealed by the IL-10/IL-12 ratio and the levels of TNF-α and IL-6. These latter effects may be attributed to the inhibition of phosphorylation-induced activation of NF-κB and a concomitant reduction in the expression of NLRP3, pro-IL-1β, and pro-IL-18. Furthermore, rosuvastatin/ reduced Ox-LDL-induced TXNIP and attenuated the inflammatory response by inhibiting NLRP3 inflammasome assembly. To conclude, rosuvastatin/Lactobacillus offers a safe and effective strategy for the management of ulcerative colitis.
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http://dx.doi.org/10.3390/ph14040341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068273PMC
April 2021

Salidroside induces cell apoptosis and inhibits the invasiveness of HT29 colorectal cells by regulating protein kinase R, NF-κB and STAT3.

Cancer Biomark 2021 ;31(1):13-25

Mansoura Research Centre for Cord Stem Cell (MARC-CSC), Stem Cells Bank, Children's Hospital, Mansoura University, Mansoura, Egypt.

Background: Protein kinase R (PKR) can suppress various types of solid tumors by inducing cellular oxidative stress and apoptosis. Likewise, Slaidorside, a plant flavonoid, was shown to have anti-tumorigenesis in many solid tumors.

Objective: This study evaluated anti-tumorigenesis of Salidroside in HT29 colorectal cancer and investigated if the underlying mechanism involves activation of PKR.

Methods: Control or PKR deficient cells were cultured in DMEM media treated with 100 μM Salidroside and cell survival, apoptosis, and other biochemical-related markers were evaluated.

Results: Salidroside significantly reduced cell survival and proliferation and increased the release of lactate dehydrogenase (LDH) and levels of single-stranded DNA (ssDNA). It also increased the protein levels of caspases 3 and 8. Concomitantly, Salidroside increased the protein level and activity of PKR and increased the expression of its downstream targets, p-eIF2α (Ser51), p53 MAPK, and p53. On the contrary, it inhibited the nuclear activation of STAT-3 and NF-κB p65. In PKR deficient cells, the partial effects of Salidroside on cell survival, proliferation, and apoptotic markers were observed coincided with no effects on the expression of eIF-2α, and JNK, p53, p38 MAPK, and caspase 8 but with a significant decrease in the nuclear activities of STAT3 and NF-κB.

Conclusion: Salidroside suppresses the tumorigenesis of HT29 CRC by increasing activation of eIF-2α and JNK and upregulation of p53, p38 MAPK, and caspase-8 through upregulating and activation of PKR. However, the tumor suppressor effect of Salidroside requires also inhibition of STAT3 and NF-κB in a PKR-independent mechanism.
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http://dx.doi.org/10.3233/CBM-203257DOI Listing
January 2021

Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R.

Saudi Pharm J 2021 Jan 14;29(1):27-42. Epub 2020 Dec 14.

Department of Biochemistry, College of Sciences, University of Jeddah, Jeddah, Saudi Arabia.

This study examined if the Fisetin against streptozotocin-induced diabetic cardiomyopathy (DC) in rats involves regulating cardiac metabolism and suppressing protein kinase R (PKR). Male rats were divided (12/groups) as control (non-diabetic), control + Fisetin, T1DM, and T1DM + Fisetin. Fisetin was administered orally at a final dose of 2.5 mg/kg for 12 weeks. In T1DM1-induced rats, Fisetin prevented heart and final body weights loss, lowered circulatory levels troponin I and creatinine kinase-MB (CK-MB), increased fasting insulin levels, and improved ventricular systolic and diastolic functions. It also preserved the structure of the cardiomyocytes and reduced oxidative stress, fibrosis, protein levels of transforming growth factor-β1 (TGF-β1), collagenase 1A, caspase-3, and the activation of JNK, p53, and p38 MAPK. In the control and diabetic rats, Fisetin attenuated fasting hyperglycaemia, the increases in glucose levels after the oral and insulin tolerance tests, and HOMA-IR. It also increased cardiac glucose oxidation by increasing the activity of private dehydrogenase (PDH), phosphofructokinase (PFK), protein levels of PPAR-α and suppressed cardiac inflammation by inhibiting NF-κB. These effects were associated with a reduction in the activity of PKR and subsequent increase in the activity of eeukaryotic initiation factor 2 (eIF2) with a parallel increase in protein levels of p67, a cellular inhibitor of PKR. In cultured cardiomyocytes, Fisetin, prevented high glucose (HG)-induced activation of PKR and reduction in p67, in a dose-dependent manner. However, the effect of Fisetin on PKR was diminished in LG and HG-treated cardiomyocytes with p67-siRNA. In conclusion, Fisetin protects against DC in rats by improving cardiac glucose metabolism and suppressing PKR.
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http://dx.doi.org/10.1016/j.jsps.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873759PMC
January 2021

Acylated ghrelin protects against doxorubicin-induced nephropathy by activating silent information regulator 1.

Basic Clin Pharmacol Toxicol 2021 Jun 25;128(6):805-821. Epub 2021 Feb 25.

Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia.

This study investigated the nephroprotective role of acylated ghrelin (AG) against DOX-induced nephropathy and examined whether the protection involves silent information regulator 1 (SIRT1). Rats were divided into control, control + AG, DOX, DOX + AG, DOX + AG + [D-Lys3]-GHRP-6 (a ghrelin receptor antagonist), and DOX + AG + EX-527 (a sirt1 inhibitor). DOX was given over the first 2 weeks. AG (10 ng/kg) and both inhibitors were given as 3 doses/wk for 5 weeks. AG improved the structure and the function of the kidneys; down-regulated the renal expression of TGF-β1, collagen 1A1 and α-SMA; and inhibited the renal collagen deposition in the kidneys of DOX-treated rats. Concomitantly, it reduced the renal levels of ROS, MDA, TNF-α, and IL-6 and protein levels of cytochrome-c, TGF-β1, Smad3 and α-SMA in these rats. In both the control and DOX-treated rats, AG significantly increased the renal levels of SOD and GSH, decreased the expression of cleaved caspase-3 and Bax, increased the total levels and the nuclear activity of SIRT1 and reduced the deacetylation of p53, NF-κB and FOXO-31. All the effects were abolished by the concurrent administration of EX-527 and [D-Lys3]-GHRP-6. In conclusion, AG prevents DOX-induced nephropathy in SIRT1 and GSHRa1-dependent mechanism.
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http://dx.doi.org/10.1111/bcpt.13569DOI Listing
June 2021

Dipteran Carboxymethyl Chitosan as an Inexhaustible Derivative with a Potential Antiproliferative Activity in Hepatocellular Carcinoma Cells.

Evid Based Complement Alternat Med 2020 28;2020:4396305. Epub 2020 Sep 28.

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

Traditional folk therapies indicate that insects have diverse medicinal potentials. However, the therapeutic application of insect chitosan and its derivatives has not been explored. To investigate the application of chitosan and its derivatives, the carboxymethyl derivative of chitosan (CM-Ch) was extracted from two dipteran larvae species, and . The degree of deacetylation (DD) and CM-Ch functional groups were validated using Fourier-transform infrared (FTIR) spectroscopy analysis and proton nuclear magnetic resonance spectroscopy (H NMR), respectively. The molecular weight was estimated using MALDI-TOF MS analysis. The effect of CM-Ch on the morphology and proliferation of human liver HepG2 cancer cells was assessed. IC of CM-Ch induced significant growth-inhibitory effects in HepG2 cells. CM-Ch treatment altered the morphology of HepG2 in a dose-dependent manner and induced apoptosis in a caspase-dependent manner. CM-Ch treatment showed no signs of toxicity, and no alterations in liver and kidney biochemical markers were observed in albino rats. A CM-Ch derivative from commercial crustacean chitosan was used to assess the efficacy of the insect-derived CM-Ch. The data presented here introduce insect CM-Ch as a promising, inexhaustible, safe derivative of chitosan with antitumor potential in liver cancer. This is the first report highlighting the anticancer activity of insect CM-Ch in hepatocellular carcinoma cells.
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http://dx.doi.org/10.1155/2020/4396305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539079PMC
September 2020

Origanum vulgare L. leaves extract alleviates testis and sperm damages induced by finasteride: Biochemical, Immunohistological and apoptosis genes based evidences.

Andrologia 2020 Dec 23;52(11):e13823. Epub 2020 Sep 23.

Zoology Department, College of Science, Fayoum University, Fayoum, Egypt.

The aim of the current study was to investigate antioxidant, anti-inflammatory and anti-apoptotic effects of Origanum vulgare on finasteride-induced oxidative injury in mouse testis and sperm parameters. Thirty BALB/c mice were divided into 5 groups: negative control, received 0.5 ml/day distilled water; positive control, received 25 mg/kg finasteride orally; and three groups received 100, 200 and 400 mg/kg/day O. vulgare extract plus 25 mg kg  day finasteride for 35 days. At day 36, serum luteinising hormone, follicle-stimulating hormone and testosterone, inflammatory cytokines (IL-6, TNF-α, IL-1β), glutathione peroxidase, superoxide dismutase and nitric oxide levels were assessed. Also, apoptotic changes investigated through genes expression and immunohistochemical staining. Finasteride in 35 days resulted in significant destructive alterations in the testis architecture, suppressed antioxidant enzymes and increased lipid peroxidation. The expression of Bcl-2 was down-regulated, whereas p53 and caspase-3 were up-regulated. Origanum vulgare improved the serum level of hormones and restored the antioxidant defence. 200 and 400 mg/kg/day of O. vulgare alleviated the testis structure and sperm parameters, up-regulated the anti-apoptotic gene Bcl-2 and down-regulated the p53, caspase-3 genes in treated groups. The findings indicate that O. vulgare extract improved function and structure of testis tissue against finasteride-induced testicular toxicity.
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http://dx.doi.org/10.1111/and.13823DOI Listing
December 2020

The Possible Neuroprotective Effect of Silymarin against Aluminum Chloride-Prompted Alzheimer's-Like Disease in Rats.

Brain Sci 2020 Sep 11;10(9). Epub 2020 Sep 11.

Department of Biological and Geological Sciences, Faculty of Education, Ain Shams University, Cairo 11566, Egypt.

Alzheimer's disease (AD) is a worldwide rapidly growing neurodegenerative disease. Here, we elucidated the neuroprotective effects of silymarin (SM) on the hippocampal tissues of aluminum chloride (AlCl)-induced Alzheimer-like disease in rats using biochemical, histological, and ultrastructural approaches. Forty rats were divided into control, SM, AlCl, and AlCl + SM groups. Biochemically, AlCl administration resulted in marked elevation in levels of lipid peroxidation (LPO) and nitric oxide (NO) and decrease in levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Moreover, AlCl significantly increased tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), and acetylcholinesterase (AChE) activities. Furthermore, myriad histological and ultrastructural alterations were recorded in the hippocampal tissues of AlCl-treated rats represented as marked degenerative changes of pyramidal neurons, astrocytes, and oligodendrocytes. Additionally, some myelinated nerve fibers exhibited irregular arrangement of their myelin coats, while the others revealed focal degranulation of their myelin sheaths. Severe defects in the blood-brain barrier (BBB) were also recorded. However, co-administration of SM with AlCl reversed most of the biochemical, histological, and ultrastructural changes triggered by AlCl in rats. The results of the current study indicate that SM can potentially mend most of the previously evoked neuronal damage in the hippocampal tissues of AlCl-kindled rats.
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http://dx.doi.org/10.3390/brainsci10090628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564174PMC
September 2020

The anti-tumourigenic effect of ellagic acid in SKOV-3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK.

Clin Exp Pharmacol Physiol 2020 09 23;47(9):1611-1621. Epub 2020 Jun 23.

Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt.

This study investigated the effect of ellagic acid (EA) on SKOV-3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin-like growth factor-1 (IGF-1), a PI3K/Akt activator. EA, at an IC of 36.6 µmol/L, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV-3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin-1, ATG-5, LC3I/II, Bax, cleaved caspase-3/8 and reduced those of p62 and Bcl-2 in these cancer cells. Mechanistically, EA decreased levels of p-S6K1 (Thr ) and 4EBP-1 (Thr ), two downstream targets of mTORC1, and p-Akt (Thr ) but increased levels of AMPK (Thr ) and p-raptor (Ser ), a natural inhibitor of mTORC1. CC or IGF-1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin-1, and cleaved caspase-3. In conclusion, EA can inhibit SKOV-3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK.
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http://dx.doi.org/10.1111/1440-1681.13338DOI Listing
September 2020

The Protective Role of Toll-Like Receptor Agonist Monophosphoryl Lipid A Against Vaccinated Murine Schistosomiasis.

Acta Parasitol 2020 Sep 2;65(3):652-660. Epub 2020 Apr 2.

Biology Department, Faculty of Science, King Khalid University, PO Box 9004, Abha, 61413, Saudi Arabia.

Purpose: Schistosomiasis is a disease that afflicts over 220 million people worldwide. To date, there is no vaccine against schistosomiasis and chemotherapy relies basically on a single drug, praziquantel. The current study was undertaken to investigate the therapeutic effects of monophosphoryl lipid A (MPLA) as an adjuvant in soluble egg antigen (SEA)-vaccinated and Schistosoma mansoni-infected mice.

Methods: Mice were divided into two groups of uninfected and Schistosoma mansoni infected. The two groups were treated differently with MPLA, SEA and praziquantel. Study parameters included parasitological, immunological and biochemical parameters.

Results: Parasitological parameters revealed that intraperitoneal injection of MPLA into SEA-vaccinated and S. mansoni-infected mice was effective in reducing the worm and egg burden, granuloma count and diameter as well as the total area of infection in their livers versus SEA-untreated but infected ones. In addition, MPLA showed ameliorative action on the elevated liver oxidative stress marker, including malondialdehyde (MDA) and a decrease in the level of the antioxidant enzymes, reduced glutathione (GSH) and catalase (CAT) which may have a role in the liver damage and fibrosis due to S. mansoni infection.

Conclusion: Treatment with MPLA has multi-functions in attenuating the deleterious impacts of S. mansoni infection in mice livers. Its effects are mediated through a reduction of ova count, worm burden, granuloma diameter and amelioration of antioxidant defense systems, and liver function biomarkers.
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http://dx.doi.org/10.2478/s11686-020-00204-3DOI Listing
September 2020

Protective effects of thymoquinone and diallyl sulphide against malathion-induced toxicity in rats.

Environ Sci Pollut Res Int 2020 Apr 13;27(10):10228-10235. Epub 2020 Jan 13.

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.

Malathion is a potent organophosphate insecticide that inhibits acetylcholinesterase (AChE) enzyme. Our experimental objective was to investigate the beneficial effects of diallyl sulphide (DAS) and thymoquinone (TQ) against malathion-induced oxidative stress in rat cerebral, hepatic, and renal tissues. For 30 days, rats received corn oil alone (negative control) or malathion by intragastric gavage (200 mg/kg daily), either alone (positive control) or combined with oral DAS (200 mg/kg daily) or TQ (10 mg/kg daily) (treatment groups). Later, blood samples were collected via direct cardiac puncture and tissue samples were obtained for biochemical analysis. Malathion administration was associated with significant increases (p < 0.05) in the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase, cholesterol, urea, creatinine, and 8-OHdG (DNA damage biomarker), as well as significant (p < 0.05) decreases in the serum levels of total proteins, albumin, triglycerides, and AChE. Moreover, it significantly increased the tissue concentrations of malondialdehyde and nitric oxide and reduced tissue glutathione concentration and activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). Treatment of malathion-intoxicated rats with DAS or TQ significantly minimized these biochemical and oxidative effects with more frequent reversal to normal ranges of serum biomarkers, tissue oxidative markers, and antioxidant enzymes in the TQ group. In conclusion, treatment with DAS or TQ ameliorated the biochemical and oxidative effects of malathion, probably through reducing the generation of reactive oxygen and nitrogen radicals, as well as enhancing the antioxidant defense mechanisms.
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http://dx.doi.org/10.1007/s11356-019-07580-yDOI Listing
April 2020

Berberine chloride ameliorated PI3K/Akt-p/SIRT-1/PTEN signaling pathway in insulin resistance syndrome induced in rats.

J Food Biochem 2019 12 11;43(12):e13049. Epub 2019 Sep 11.

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

The liver is the main organ involved in lipid metabolism process and it helps in drug detoxification. Insulin resistance is considered one of risk reasons which lead to several metabolic diseases. Currently, berberine (BER) occupies a huge challenge against multiple diseases with no toxic effect. The present work was aimed to identify, does BER-chloride has a poisonous influence on the liver? and investigating the outcome of BER-chloride on PI3K/Akt-p/SIRT-1/PTEN pathway during insulin resistance syndrome. The insulin resistance model was achieved in experimental female rats via high-fat diet (HFD). Glucose, insulin, lipid profiles, and hepatic oxidative stress parameters were assessed. PI3K, AKt-p, SIRT-1, and PTEN levels in hepatic tissue were determined at genome and protein levels. Further adiponectin concentration was performed in serum, hepatic, and white adipose tissues. Molecular study of fold alteration in insulin, insulin receptor, and retinol binding protein-4 (RBP4) in liver was done. PRACTICAL APPLICATIONS: Obesity syndrome causes multiple obstacles in modern years. The current results revealed elevation the body weight of rats, plasma glucose, homeostatic model assessment, glycated hemoglobin, insulin, and lipid profiles concentrations in a group of rats, which nourished HFD for 8 weeks and this rise, was diminished after 2 weeks from BER-chloride administration. Further, BER-chloride improved transaminases enzymes, pro-oxidant, and antioxidant defense system, PI3K, AKt-p, SIRT-1, and PTEN in the liver, with downregulation of hepatic RBP4. Hence, these data provide a crucial message that BER-chloride enhanced both hepatic function and insulin signaling pathways that might be of therapeutic importance to insulin resistance with no harmful effect on the liver. BER-chloride is predicted to be a drug of choice for obesity complications cure.
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http://dx.doi.org/10.1111/jfbc.13049DOI Listing
December 2019

Chemoprevention of rat mammary carcinogenesis by spirulina.

Am J Pathol 2014 Jan 21;184(1):296-303. Epub 2013 Nov 21.

Department of Obstetrics and Gynecology, Stanley S. Scott Cancer; Louisiana State University Health Science Center, New Orleans, Louisiana.

Spirulina (SP) (Arthrospira platensis; previously Spirulina platensis) is a filamentous blue-green microalga (cyanobacterium) with potent dietary phytoantioxidant and anticancerous properties. We investigated the chemopreventive effect of SP against 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat breast carcinogenesis, and further studied its underlying mechanisms of action in vitro. Remarkably, SP cleared DMBA-induced rat mammary tumors, which was clearly confirmed by morphological and histological methods. SP supplementation reduced the incidence of breast tumors from 87% to 13%. At the molecular level, immunohistochemical analysis revealed that SP supplementation reduced expression of both Ki-67 and estrogen α. More interestingly, molecular analysis in the in vitro experiments indicated that SP treatment inhibited cell proliferation by 24 hours, which was accompanied by increased p53 expression, followed by increased expression of its downstream target gene, Cdkn1a (alias p21 or p21(Waf1/Cip1)). In addition, SP increased Bax and decreased Bcl-2 expression, indicating induction of apoptosis by 48 hours after SP treatment. To our knowledge, this is the first report of in vivo chemopreventive effect of SP against DMBA-induced breast carcinogenesis in rat, supporting its potential use in chemoprevention of cancer.
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http://dx.doi.org/10.1016/j.ajpath.2013.10.025DOI Listing
January 2014

Proliferating cell nuclear antigen (PCNA) overexpression and microvessel density predict survival in the urinary bladder carcinoma.

Int Urol Nephrol 2006 ;38(2):237-42

Faculty of Medicine, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Objective: To study proliferating cell nuclear antigen (PCNA) over expression and angiogenesis with their relationship to tumor parameters in squamous cell carcinoma of the urinary bladder in patients who underwent radical cystectomy.

Patients And Methods: The mean age of the patients was 53.53 years (range; 29-70 years) and the males were 98 of 154. Sections from paraffin embedded tissues were retrieved and stained with antibodies against PCNA for proliferation and CD34 for angiogenesis using immunohistochemical technique. Fisher's exact test was used to evaluate the relationship between categorical variables and the Kaplan-Meier procedure was used to assess survival outcomes. The Cox regression model was used for multivariate analysis.

Results: The median follow up period was 65 months. microvessel density (MVD), PCNA, tumor grade, P-stage, DNA ploidy, lymph node status had a significant impact on the 5-year survival of patients in univariate analysis. In Cox proportional hazard model, MVD, PCNA, DNA ploidy and stage sustained their significant impact on survival of the patients.

Conclusions: MVD, PCNA, DNA ploidy and stage are independent prognostic factors in patients with squamous cell carcinoma of the urinary bladder.
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http://dx.doi.org/10.1007/s11255-005-4760-6DOI Listing
March 2007

Histogenesis of human renal cell carcinoma by using electron microscopy and immunohistochemical techniques.

Int Urol Nephrol 2005 ;37(3):439-45

Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Electron microscopy and immunohistochemical techniques are powerful tools for the determination of tissue origin. Both techniques have been used in the current experiment for histogenesis of renal cell carcinoma. Fifty kidney tumors were subjected to immunohistochemical detection for intermediate filaments cytokeratin and vimentin, which are normally expressed in epithelial tissue and mesenchymal tissues, respectively. Twenty cases of the above were examined by electron microscopy for detection of ultrastructure features. From each kidney, two specimens were taken, one from the diseased area and another far from it to serve as a control. Immunohistochemical study revealed in cases of renal cell carcinoma, cytokeratin and vimentin were expressed alone in 44% of cases, and 40% of cases, respectively. Twelve percent of cases were coexpressed with both cytokeratin and vimentin. Electron microscopic study of diseased specimens revealed the expression of desmosomes which was observed in almost all tumor specimens. The expression of the vimentin in some cases either alone or with cytokeratin was interpreted as a change in the characters of some tumor cells which indicates the need for additional techniques in such cases to get the proper interpretation. The prevalence of the expression of cytokeratin and the persistence existence of desmosomes indicate the epithelial origin of the tumor. This data is very beneficial for determination of line of therapy and follow up of the patients. The results confirm the power of combined use of both immunohistochemistry and electron microscopy in the field of histogenesis.
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http://dx.doi.org/10.1007/s11255-004-6103-4DOI Listing
March 2006