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Gouda Helal

Al-Azhar University, Faculty of Pharmacy, Pharmacology and Toxicology, Faculty Member

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Carla Filomena Silva

Western University Canada

Tufts University

Iran University of Medical Sciences

Michele Calvano

Università degli Studi "La Sapienza" di Roma

Brent Mittelstadt

University of Oxford

Dr Alexandra-Paraskevi Chytiri

De Montfort University, Leicester, UK)

Izet Masic, MD, PhD, FWAAS, FEASA, FIAHSI, FEFMI, FACMI

University of Sarajevo

Mohammad Abu Fayez PGDHRM BSHRM

University of Colorado, Boulder

Wasun Chantratita

Mahidol University

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Papers by Gouda Helal

miRNAs driving diagnosis, prognosis and progression in Merkel cell carcinoma

Pathology Research and Practice, Aug 1, 2023

Ovarian cancer derived exosomes: Non-coding RNA (ncRNA) signatures and therapeutic targets

Transcriptomics: open access, Sep 9, 2016

Silencing of tissue factor by antisense deoxyoligonucleotide mitigates thioacetamide-induced liver injury

Naunyn-schmiedebergs Archives of Pharmacology, May 20, 2020

Background Retinoid receptors (RRs), RAR-α and RXR-α, work as transcription factors that regulate... more Background Retinoid receptors (RRs), RAR-α and RXR-α, work as transcription factors that regulate cell growth, differentiation, survival, and death. Hepatic stellate cells (HSCs) store retinoid and release its RRs as lipid droplets upon their activation. Purpose We test the hypothesis that loss of retinoid receptors RAR-α and RXR-α from HSCs is dependent on tissue factor (TF) during thioacetamide (TAA)-induced liver injury. Methods Liver toxicity markers, TF, fibrin, cleaved caspase-3, and cyclin D1 as well as histopathology were investigated. Results Increased TF, fibrin, cleaved caspase-3, and cyclin D1 protein expression is seen in zone of central vein after TAA injection compared with vehicle-treated mice. A strong downregulation of RAR-α and RXR-α is seen in TAA-induced liver injury. In addition, histopathological obliteration and pericentral expression of cleaved caspase 3 and cyclin D1 are observed after TAA injection compared with the normal vehicle-treated mice. No changes have been seen in TAA/TF-sense (SC) in whole parameters compared with TAAtreated animals. TAA/TF-antisense (AS)-treated mice show normal expression of all parameters and normal histopathological features when compared with the control mice. In conclusion, this study declares that the strong downregulation of RAR-α and RXR-α may cause liver injury and particularly activation of HSCs in TAA-induced toxicity. TF-AS treatment not only downregulates TF protein expression but also alleviates loss of liver RAR-α and RXR-α and suppresses the activated apoptosis signals in TAA-induced liver toxicity. Finally, TF and RAR-α/RXR-α are important regulatory molecules in TAA induced acute liver injury.

Taurine upregulated 1: Prognostic biomarker in breast cancer

Archives of Pharmaceutical Sciences Ain Shams University, Dec 1, 2022

The most common kind of cancer and the second leading cause of cancer mortality in women is breas... more The most common kind of cancer and the second leading cause of cancer mortality in women is breast cancer (BC). The most proven cause of mortality in BC patients comprises tumor metastasis and invasive development. Long noncoding RNAs are endangered by many crucial mechanisms involved in BC metastasis (lncRNAs). RNAs that are classified as lncRNAs are thought to be longer than 200 nucleotides in length. Literature has long shown that lncRNAs are promising therapeutic targets in BC as well as diagnostic and prognostic indicators. Only a few studies have, to our knowledge, described the bioenergetics of taurine upregulated 1 (TUG1). Human cancer has been linked to a new lncRNA called TUG1. TUG1 has drawn increasing interest in recent years and has been shown to express abnormality in several forms of cancer. Numerous research suggested that the development of tumefaction and cell metabolism may be favorably correlated with TUG1. As a result, we aimed to concentrate on recent developments in the primary molecular processes of TUG1 in cancer in this review. This includes its role in drug resistance, invasion, cell migration, apoptosis, and proliferation. Most recent investigations asserted that TUG was overexpressed in BC tissues and cell lines as compared to their normal counterparts. To better understand the critical impact of tamoxifen (TMX) resistance and improve quality of life (QOL), researchers are looking for an early diagnostic marker.

Taurine upregulated 1: Prognostic biomarker in breast cancer

Archives of Pharmaceutical Sciences Ain Shams University

The most common kind of cancer and the second leading cause of cancer mortality in women is breas... more The most common kind of cancer and the second leading cause of cancer mortality in women is breast cancer (BC). The most proven cause of mortality in BC patients comprises tumor metastasis and invasive development. Long noncoding RNAs are endangered by many crucial mechanisms involved in BC metastasis (lncRNAs). RNAs that are classified as lncRNAs are thought to be longer than 200 nucleotides in length. Literature has long shown that lncRNAs are promising therapeutic targets in BC as well as diagnostic and prognostic indicators. Only a few studies have, to our knowledge, described the bioenergetics of taurine upregulated 1 (TUG1). Human cancer has been linked to a new lncRNA called TUG1. TUG1 has drawn increasing interest in recent years and has been shown to express abnormality in several forms of cancer. Numerous research suggested that the development of tumefaction and cell metabolism may be favorably correlated with TUG1. As a result, we aimed to concentrate on recent developments in the primary molecular processes of TUG1 in cancer in this review. This includes its role in drug resistance, invasion, cell migration, apoptosis, and proliferation. Most recent investigations asserted that TUG was overexpressed in BC tissues and cell lines as compared to their normal counterparts. To better understand the critical impact of tamoxifen (TMX) resistance and improve quality of life (QOL), researchers are looking for an early diagnostic marker.

Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart

Pharmacological Research, Nov 1, 2003

The therapeutic value of doxorubicin (DOX) as anticancer antibiotic is limited by its cardiotoxic... more The therapeutic value of doxorubicin (DOX) as anticancer antibiotic is limited by its cardiotoxicity. The implication of natural phenolic acids in the prevention of many pathologic diseases has been reported. Herein, the ability of p-coumaric (PC) acid, a member of phenolic acids, to protect rat's heart against DOX-induced oxidative stress was investigated. Three main groups of albino rats were used; DOX, PC, and PC plus DOX-receiving animals. Corresponding control animals were also used. DOX was administered i.p. in a single dose of 15 mg kg −1. PC alone, in a dose of 100 mg kg −1 , was orally administered for five consecutive days. In PC/DOX group, rats received PC 5 days prior to DOX. DOX-induced high serum levels of lactic dehydrogenase (LDH) and creatine phosphokinase (CPK), were reduced significantly by PC administration, compared to DOX-receiving rats. Pretreatment with PC ameliorated the cardiac content of glutathione (GSH), and superoxide dismutase (SOD) & catalase (CAT) activities, compared to DOX-receiving rats. On the other hand, accumulation of cardiac content of MDA significantly decreased following PC pretreatment, compared to DOX-treated rats. The data presented here indicate that PC protects rats hearts against DOX-induced oxidative stress in the heart. It may be worthy to consider the usefulness of PC as adjuvant therapy in cancer management.

Neurotrophins and Their Receptors in Nerve Injury and Repair

Neurochemistry International, 1997

<ytokines are a heterogeneous group of polypeptide mediators that have been associated with activ... more

The role of mitochondrial/metabolic axis in development of tamoxifen resistance in breast cancer

Human Cell

Only a few investigations, to our knowledge, have examined the bioenergetics of Tamoxifen (TMX) r... more Only a few investigations, to our knowledge, have examined the bioenergetics of Tamoxifen (TMX) resistant individuals and reported altered mitochondrial activity and metabolic profile. The primary cause of TMX resistance is firmly suggested to be metabolic changes. Metabolic variations and hypoxia have also been linked in a bidirectional manner. Increased hypoxic levels correlate with early recurrence and proliferation and have a negative therapeutic impact on breast cancer (BC) patients. Hypoxia, carcinogenesis, and patient death are all correlated, resulting in more aggressive traits, a higher chance of metastasis, and TMX resistance. Consequently, we sought to investigate the possible role of the metabolic/hypoxial axis Long non-coding RNA (LncRNA) Taurine up-regulated 1 (TUG-1), Micro-RNA 186-5p (miR-186), Sirtuin-3 (SIRT3), Peroxisome Proliferator Activator Receptor alpha (PPAR-α), and Hypoxia-Inducible Factor-1 (HIF-1) in the development of TMX resistance in BC patients and to...

The potential role of miRNAs in the pathogenesis of adrenocortical carcinoma – A focus on signaling pathways interplay

Pathology - Research and Practice

Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer

Scientific Reports, Sep 27, 2022

Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation

American Journal of Obstetrics and Gynecology, 2003

Objective: Intrauterine and maternal systemic infections are proposed causes of preterm labor. Th... more Objective: Intrauterine and maternal systemic infections are proposed causes of preterm labor. The resulting prematurity is associated with 75% of infant mortality and 50% of long-term neurologic handicaps. We hypothesize that free radicals generated in large quantities during an inflammatory response shift the fetomaternal redox balance to an oxidative state, compromising the fetus. Thus, if our working hypothesis is correct,

Bacterial Lipopolysaccharide Vigorously Activate JAK2/STAT3 Induced Rheumatoid Arthritis Collate with Complete Freund’s Adjuvant in Experimental Rats

Biomedical and Pharmacology Journal, 2017

The Janus kinase-signal transducers and activators of transcription (JAK/STAT) is one of signalin... more The Janus kinase-signal transducers and activators of transcription (JAK/STAT) is one of signaling pathways that mediate rheumatoid arthritis (RA) pathogenesis. Present study designed to evaluate the stimulatory role of lipopolysaccharide (LPS) on JAK2/STAT3-induced RA, compared to the traditional Complete Freund’s Adjuvant (CFA)-induced RA. Rats were allocated into normal control group (saline only), CFA arthritic control groups (0.4 ml/3days/12days, S.C.), and LPS group (100μg/kg/day/12days, I.P.). After 12 days of induction, tissue samples were collected for assessment of tissue phosphorylated JAK2 and STAT3, while serum samples used for biochemical evaluation of interleukin-6 (IL-6) and anti-citrullinated protein antibody (ACPA). Results indicated that LPS significantly increased tissue phosphorylation of JAK2 and STAT3 in cope with significant increase in serum IL-6 and ACPA as compared to CFA. Conclusively, LPS can consider as a formidable inducer for RA, in partly through act...

Carbon tetrachloride-induced liver injury in mice is tissue factor dependent

Environmental Toxicology and Pharmacology, 2015

Tissue factor (TF) is a membranous glycoprotein that activates the coagulation system when blood ... more Tissue factor (TF) is a membranous glycoprotein that activates the coagulation system when blood vessels or tissues are damaged. TF was up-regulated in monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. The present study aimed to test the hypothesis that TF-dependent fibrin deposition occurs in liver toxicity induced by CCl 4 in mice. Pericentral deposition of TF and fibrin is resulted after CCl 4-induced liver toxicity. The toxicity was evaluated by determination of serum activities of ALT, AST and ALP as well as GSH content and histopathological changes. The results showed that injection of mice with TF-antisense deoxyoligonucleotide (TF-AS) prevented the accumulation of TF and fibrin in the hepatic tissues. Furthermore, it significantly restored blood biochemical parameters, GSH content and distorted histopathological features caused by CCl 4. The current study demonstrates that TF activation is associated with CCl 4-induced liver injury. Furthermore, administration of TF-AS successfully prevented this type of liver injury.

Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats

Pakistan Journal of Pharmaceutical Sciences, 2010

Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to... more Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to multiple organ failure. This study was carried out to investigate the effects of thymoquinone (TQ), the main constituent of Nigella sativa seeds, against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione (GSH) and significantly increased the level of malondialdehyde (MDA) and the activity of caspase-3 enzyme in the liver. Serum tumour necrosis factor-alpha (TNF-alpha) and bilirubin levels and the activities of alkaline phosphatase (ALP) and gamma-glutamyl transferase (gamma-GT) enzymes were markedly increased in LPS-treated rats. TQ supplementation resulted in normalization of liver GSH and decreases in the levels of MDA and caspase-3 activity in the liver with reduction of serum TNF-alpha, serum total bilirubin and the activities of ALP and gamma-GTenzymes. Histopathological examination revealed that TQ administration improved L...

Clinical evaluation of some sofosbuvir-based regimens for the treatment of hepatitis c in private healthcare sector in Egypt

Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats

Pakistan journal of pharmaceutical sciences, 2010

Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to... more Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to multiple organ failure. This study was carried out to investigate the effects of thymoquinone (TQ), the main constituent of Nigella sativa seeds, against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione (GSH) and significantly increased the level of malondialdehyde (MDA) and the activity of caspase-3 enzyme in the liver. Serum tumour necrosis factor-alpha (TNF-alpha) and bilirubin levels and the activities of alkaline phosphatase (ALP) and gamma-glutamyl transferase (gamma-GT) enzymes were markedly increased in LPS-treated rats. TQ supplementation resulted in normalization of liver GSH and decreases in the levels of MDA and caspase-3 activity in the liver with reduction of serum TNF-alpha, serum total bilirubin and the activities of ALP and gamma-GTenzymes. Histopathological examination revealed that TQ administration improved L...

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology, 2021

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis... more Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in N-acetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS pre...

Association between interleukin 28B polymorphism and sustained virological response to sofosbuvir plus daclatasvir in chronic hepatitis C genotype 4 Egyptian patients

Journal of Clinical Pharmacy and Therapeutics, 2021

Sofosbuvir has been approved as the first nonstructural protein 5B polymerase inhibitor with pan‐... more Sofosbuvir has been approved as the first nonstructural protein 5B polymerase inhibitor with pan‐genotypic activity against the hepatitis C (HCV) virus. Daclatasvir is a first‐in‐class hepatitis C virus nonstructural protein 5A replication complex inhibitor. We aimed to evaluate the usefulness of the reference single nucleotide polymorphism (rs12979860) interleukin 28B (CC genotype) for predicting sustained virological response to sofosbuvir plus daclatasvir in Egyptian patients infected with HCV‐4.

Antioxidants Reveal Protection against the Biochemical Changes in Liver, Kidney and Blood Profiles after Clindamycin / Ibuprofen Administration in Dental Patients

World Academy of Science, Engineering and Technology, International Journal of Medical, Health, Biomedical, Bioengineering and Pharmaceutical Engineering, 2014

The adverse effects of Clindamycin (Clind.) / Ibuprofen (Ibu.) combination on liver, kidney, bloo... more The adverse effects of Clindamycin (Clind.) / Ibuprofen (Ibu.) combination on liver, kidney, blood elements and the significances of antioxidants (N-acetylcysteine and Zinc) against these effects were evaluated. The study includes: Group I; control n=30, Group II; patients on Clind.300mg/Ibu.400mg twice daily for a week n=30, Group III; patients on Clind.300mg/Ibu.400mg+Nacetylcysteine 200mg twice daily for a week n=15 and Group IV; patients on Clind.300mg/Ibu.400mg+Zinc50mg twice daily for a week n=15. Serum malondialdehyde (MDA), alanine transferase (ALT), aspartate transferase (AST), γ glutamyl transferase (GGT), creatinine, blood urea nitrogen (BUN) were measured. Applying one way ANOVA followed by Tuckey Kramer post test, Group II showed significant increase in ALT, AST, GGT, BUN and decrease in Hb, RBCs, platelets than Group I. Group III showed significant decrease in ALT, AST, GGT, BUN than Group II. Moreover, Group IV showed significant decrease in ALT, AST, GGT and increase...

Claudin-4 induction could improve the homing and anti-fibrotic effect of bone marrow mesenchymal stem cells (BM-MSCS) in thioacetamide induced liver fibrosis in rats

Homing and migration of bone marrow mesenchymal stem cells (BM-MSCs) to a target tissue has been ... more Homing and migration of bone marrow mesenchymal stem cells (BM-MSCs) to a target tissue has been a major concern because, only few cells reach the target tissue and remain there after systemic administration. The current study aimed at investigating the potential hepatoprotective role of claudin-4 in improving the homing and antifibrotic effect of BM-MSCs. In our study, Sprague-Dawley rats were randomly divided into six groups: Control group; Meloxicam group; Thioacetamide group; Thioacetamide + BM-MSCs group; Meloxicam + Thioacetamide group; Thioacetamide + Meloxicam + BM-MSCs. Flowcytometry, Western Blot, hematoxylin and eosin (H&E), Masson’s trichrome staining, immunohistochemical studies for the detection of α-Smooth muscle actin (α-SMA) and enzyme-linked immunosorbent assay (ELISA) were involved to measure different parameters. Results showed that in vivo BM-MSCs administration significantly improved histopathological changes and attenuated the elevated liver enzymes, lipid per...

miRNAs driving diagnosis, prognosis and progression in Merkel cell carcinoma

Pathology Research and Practice, Aug 1, 2023

Ovarian cancer derived exosomes: Non-coding RNA (ncRNA) signatures and therapeutic targets

Transcriptomics: open access, Sep 9, 2016

Silencing of tissue factor by antisense deoxyoligonucleotide mitigates thioacetamide-induced liver injury

Naunyn-schmiedebergs Archives of Pharmacology, May 20, 2020

Background Retinoid receptors (RRs), RAR-α and RXR-α, work as transcription factors that regulate... more Background Retinoid receptors (RRs), RAR-α and RXR-α, work as transcription factors that regulate cell growth, differentiation, survival, and death. Hepatic stellate cells (HSCs) store retinoid and release its RRs as lipid droplets upon their activation. Purpose We test the hypothesis that loss of retinoid receptors RAR-α and RXR-α from HSCs is dependent on tissue factor (TF) during thioacetamide (TAA)-induced liver injury. Methods Liver toxicity markers, TF, fibrin, cleaved caspase-3, and cyclin D1 as well as histopathology were investigated. Results Increased TF, fibrin, cleaved caspase-3, and cyclin D1 protein expression is seen in zone of central vein after TAA injection compared with vehicle-treated mice. A strong downregulation of RAR-α and RXR-α is seen in TAA-induced liver injury. In addition, histopathological obliteration and pericentral expression of cleaved caspase 3 and cyclin D1 are observed after TAA injection compared with the normal vehicle-treated mice. No changes have been seen in TAA/TF-sense (SC) in whole parameters compared with TAAtreated animals. TAA/TF-antisense (AS)-treated mice show normal expression of all parameters and normal histopathological features when compared with the control mice. In conclusion, this study declares that the strong downregulation of RAR-α and RXR-α may cause liver injury and particularly activation of HSCs in TAA-induced toxicity. TF-AS treatment not only downregulates TF protein expression but also alleviates loss of liver RAR-α and RXR-α and suppresses the activated apoptosis signals in TAA-induced liver toxicity. Finally, TF and RAR-α/RXR-α are important regulatory molecules in TAA induced acute liver injury.

Taurine upregulated 1: Prognostic biomarker in breast cancer

Archives of Pharmaceutical Sciences Ain Shams University, Dec 1, 2022

The most common kind of cancer and the second leading cause of cancer mortality in women is breas... more The most common kind of cancer and the second leading cause of cancer mortality in women is breast cancer (BC). The most proven cause of mortality in BC patients comprises tumor metastasis and invasive development. Long noncoding RNAs are endangered by many crucial mechanisms involved in BC metastasis (lncRNAs). RNAs that are classified as lncRNAs are thought to be longer than 200 nucleotides in length. Literature has long shown that lncRNAs are promising therapeutic targets in BC as well as diagnostic and prognostic indicators. Only a few studies have, to our knowledge, described the bioenergetics of taurine upregulated 1 (TUG1). Human cancer has been linked to a new lncRNA called TUG1. TUG1 has drawn increasing interest in recent years and has been shown to express abnormality in several forms of cancer. Numerous research suggested that the development of tumefaction and cell metabolism may be favorably correlated with TUG1. As a result, we aimed to concentrate on recent developments in the primary molecular processes of TUG1 in cancer in this review. This includes its role in drug resistance, invasion, cell migration, apoptosis, and proliferation. Most recent investigations asserted that TUG was overexpressed in BC tissues and cell lines as compared to their normal counterparts. To better understand the critical impact of tamoxifen (TMX) resistance and improve quality of life (QOL), researchers are looking for an early diagnostic marker.

Taurine upregulated 1: Prognostic biomarker in breast cancer

Archives of Pharmaceutical Sciences Ain Shams University

The most common kind of cancer and the second leading cause of cancer mortality in women is breas... more The most common kind of cancer and the second leading cause of cancer mortality in women is breast cancer (BC). The most proven cause of mortality in BC patients comprises tumor metastasis and invasive development. Long noncoding RNAs are endangered by many crucial mechanisms involved in BC metastasis (lncRNAs). RNAs that are classified as lncRNAs are thought to be longer than 200 nucleotides in length. Literature has long shown that lncRNAs are promising therapeutic targets in BC as well as diagnostic and prognostic indicators. Only a few studies have, to our knowledge, described the bioenergetics of taurine upregulated 1 (TUG1). Human cancer has been linked to a new lncRNA called TUG1. TUG1 has drawn increasing interest in recent years and has been shown to express abnormality in several forms of cancer. Numerous research suggested that the development of tumefaction and cell metabolism may be favorably correlated with TUG1. As a result, we aimed to concentrate on recent developments in the primary molecular processes of TUG1 in cancer in this review. This includes its role in drug resistance, invasion, cell migration, apoptosis, and proliferation. Most recent investigations asserted that TUG was overexpressed in BC tissues and cell lines as compared to their normal counterparts. To better understand the critical impact of tamoxifen (TMX) resistance and improve quality of life (QOL), researchers are looking for an early diagnostic marker.

Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart

Pharmacological Research, Nov 1, 2003

The therapeutic value of doxorubicin (DOX) as anticancer antibiotic is limited by its cardiotoxic... more The therapeutic value of doxorubicin (DOX) as anticancer antibiotic is limited by its cardiotoxicity. The implication of natural phenolic acids in the prevention of many pathologic diseases has been reported. Herein, the ability of p-coumaric (PC) acid, a member of phenolic acids, to protect rat's heart against DOX-induced oxidative stress was investigated. Three main groups of albino rats were used; DOX, PC, and PC plus DOX-receiving animals. Corresponding control animals were also used. DOX was administered i.p. in a single dose of 15 mg kg −1. PC alone, in a dose of 100 mg kg −1 , was orally administered for five consecutive days. In PC/DOX group, rats received PC 5 days prior to DOX. DOX-induced high serum levels of lactic dehydrogenase (LDH) and creatine phosphokinase (CPK), were reduced significantly by PC administration, compared to DOX-receiving rats. Pretreatment with PC ameliorated the cardiac content of glutathione (GSH), and superoxide dismutase (SOD) & catalase (CAT) activities, compared to DOX-receiving rats. On the other hand, accumulation of cardiac content of MDA significantly decreased following PC pretreatment, compared to DOX-treated rats. The data presented here indicate that PC protects rats hearts against DOX-induced oxidative stress in the heart. It may be worthy to consider the usefulness of PC as adjuvant therapy in cancer management.

Neurotrophins and Their Receptors in Nerve Injury and Repair

Neurochemistry International, 1997

<ytokines are a heterogeneous group of polypeptide mediators that have been associated with activ... more

The role of mitochondrial/metabolic axis in development of tamoxifen resistance in breast cancer

Human Cell

Only a few investigations, to our knowledge, have examined the bioenergetics of Tamoxifen (TMX) r... more Only a few investigations, to our knowledge, have examined the bioenergetics of Tamoxifen (TMX) resistant individuals and reported altered mitochondrial activity and metabolic profile. The primary cause of TMX resistance is firmly suggested to be metabolic changes. Metabolic variations and hypoxia have also been linked in a bidirectional manner. Increased hypoxic levels correlate with early recurrence and proliferation and have a negative therapeutic impact on breast cancer (BC) patients. Hypoxia, carcinogenesis, and patient death are all correlated, resulting in more aggressive traits, a higher chance of metastasis, and TMX resistance. Consequently, we sought to investigate the possible role of the metabolic/hypoxial axis Long non-coding RNA (LncRNA) Taurine up-regulated 1 (TUG-1), Micro-RNA 186-5p (miR-186), Sirtuin-3 (SIRT3), Peroxisome Proliferator Activator Receptor alpha (PPAR-α), and Hypoxia-Inducible Factor-1 (HIF-1) in the development of TMX resistance in BC patients and to...

The potential role of miRNAs in the pathogenesis of adrenocortical carcinoma – A focus on signaling pathways interplay

Pathology - Research and Practice

Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer

Scientific Reports, Sep 27, 2022

Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation

American Journal of Obstetrics and Gynecology, 2003

Objective: Intrauterine and maternal systemic infections are proposed causes of preterm labor. Th... more Objective: Intrauterine and maternal systemic infections are proposed causes of preterm labor. The resulting prematurity is associated with 75% of infant mortality and 50% of long-term neurologic handicaps. We hypothesize that free radicals generated in large quantities during an inflammatory response shift the fetomaternal redox balance to an oxidative state, compromising the fetus. Thus, if our working hypothesis is correct,

Bacterial Lipopolysaccharide Vigorously Activate JAK2/STAT3 Induced Rheumatoid Arthritis Collate with Complete Freund’s Adjuvant in Experimental Rats

Biomedical and Pharmacology Journal, 2017

The Janus kinase-signal transducers and activators of transcription (JAK/STAT) is one of signalin... more The Janus kinase-signal transducers and activators of transcription (JAK/STAT) is one of signaling pathways that mediate rheumatoid arthritis (RA) pathogenesis. Present study designed to evaluate the stimulatory role of lipopolysaccharide (LPS) on JAK2/STAT3-induced RA, compared to the traditional Complete Freund’s Adjuvant (CFA)-induced RA. Rats were allocated into normal control group (saline only), CFA arthritic control groups (0.4 ml/3days/12days, S.C.), and LPS group (100μg/kg/day/12days, I.P.). After 12 days of induction, tissue samples were collected for assessment of tissue phosphorylated JAK2 and STAT3, while serum samples used for biochemical evaluation of interleukin-6 (IL-6) and anti-citrullinated protein antibody (ACPA). Results indicated that LPS significantly increased tissue phosphorylation of JAK2 and STAT3 in cope with significant increase in serum IL-6 and ACPA as compared to CFA. Conclusively, LPS can consider as a formidable inducer for RA, in partly through act...

Carbon tetrachloride-induced liver injury in mice is tissue factor dependent

Environmental Toxicology and Pharmacology, 2015

Tissue factor (TF) is a membranous glycoprotein that activates the coagulation system when blood ... more Tissue factor (TF) is a membranous glycoprotein that activates the coagulation system when blood vessels or tissues are damaged. TF was up-regulated in monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. The present study aimed to test the hypothesis that TF-dependent fibrin deposition occurs in liver toxicity induced by CCl 4 in mice. Pericentral deposition of TF and fibrin is resulted after CCl 4-induced liver toxicity. The toxicity was evaluated by determination of serum activities of ALT, AST and ALP as well as GSH content and histopathological changes. The results showed that injection of mice with TF-antisense deoxyoligonucleotide (TF-AS) prevented the accumulation of TF and fibrin in the hepatic tissues. Furthermore, it significantly restored blood biochemical parameters, GSH content and distorted histopathological features caused by CCl 4. The current study demonstrates that TF activation is associated with CCl 4-induced liver injury. Furthermore, administration of TF-AS successfully prevented this type of liver injury.

Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats

Pakistan Journal of Pharmaceutical Sciences, 2010

Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to... more Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to multiple organ failure. This study was carried out to investigate the effects of thymoquinone (TQ), the main constituent of Nigella sativa seeds, against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione (GSH) and significantly increased the level of malondialdehyde (MDA) and the activity of caspase-3 enzyme in the liver. Serum tumour necrosis factor-alpha (TNF-alpha) and bilirubin levels and the activities of alkaline phosphatase (ALP) and gamma-glutamyl transferase (gamma-GT) enzymes were markedly increased in LPS-treated rats. TQ supplementation resulted in normalization of liver GSH and decreases in the levels of MDA and caspase-3 activity in the liver with reduction of serum TNF-alpha, serum total bilirubin and the activities of ALP and gamma-GTenzymes. Histopathological examination revealed that TQ administration improved L...

Clinical evaluation of some sofosbuvir-based regimens for the treatment of hepatitis c in private healthcare sector in Egypt

Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats

Pakistan journal of pharmaceutical sciences, 2010

Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to... more Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to multiple organ failure. This study was carried out to investigate the effects of thymoquinone (TQ), the main constituent of Nigella sativa seeds, against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione (GSH) and significantly increased the level of malondialdehyde (MDA) and the activity of caspase-3 enzyme in the liver. Serum tumour necrosis factor-alpha (TNF-alpha) and bilirubin levels and the activities of alkaline phosphatase (ALP) and gamma-glutamyl transferase (gamma-GT) enzymes were markedly increased in LPS-treated rats. TQ supplementation resulted in normalization of liver GSH and decreases in the levels of MDA and caspase-3 activity in the liver with reduction of serum TNF-alpha, serum total bilirubin and the activities of ALP and gamma-GTenzymes. Histopathological examination revealed that TQ administration improved L...

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology, 2021

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis... more Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in N-acetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS pre...

Association between interleukin 28B polymorphism and sustained virological response to sofosbuvir plus daclatasvir in chronic hepatitis C genotype 4 Egyptian patients

Journal of Clinical Pharmacy and Therapeutics, 2021

Sofosbuvir has been approved as the first nonstructural protein 5B polymerase inhibitor with pan‐... more Sofosbuvir has been approved as the first nonstructural protein 5B polymerase inhibitor with pan‐genotypic activity against the hepatitis C (HCV) virus. Daclatasvir is a first‐in‐class hepatitis C virus nonstructural protein 5A replication complex inhibitor. We aimed to evaluate the usefulness of the reference single nucleotide polymorphism (rs12979860) interleukin 28B (CC genotype) for predicting sustained virological response to sofosbuvir plus daclatasvir in Egyptian patients infected with HCV‐4.

Antioxidants Reveal Protection against the Biochemical Changes in Liver, Kidney and Blood Profiles after Clindamycin / Ibuprofen Administration in Dental Patients

World Academy of Science, Engineering and Technology, International Journal of Medical, Health, Biomedical, Bioengineering and Pharmaceutical Engineering, 2014

The adverse effects of Clindamycin (Clind.) / Ibuprofen (Ibu.) combination on liver, kidney, bloo... more The adverse effects of Clindamycin (Clind.) / Ibuprofen (Ibu.) combination on liver, kidney, blood elements and the significances of antioxidants (N-acetylcysteine and Zinc) against these effects were evaluated. The study includes: Group I; control n=30, Group II; patients on Clind.300mg/Ibu.400mg twice daily for a week n=30, Group III; patients on Clind.300mg/Ibu.400mg+Nacetylcysteine 200mg twice daily for a week n=15 and Group IV; patients on Clind.300mg/Ibu.400mg+Zinc50mg twice daily for a week n=15. Serum malondialdehyde (MDA), alanine transferase (ALT), aspartate transferase (AST), γ glutamyl transferase (GGT), creatinine, blood urea nitrogen (BUN) were measured. Applying one way ANOVA followed by Tuckey Kramer post test, Group II showed significant increase in ALT, AST, GGT, BUN and decrease in Hb, RBCs, platelets than Group I. Group III showed significant decrease in ALT, AST, GGT, BUN than Group II. Moreover, Group IV showed significant decrease in ALT, AST, GGT and increase...

Claudin-4 induction could improve the homing and anti-fibrotic effect of bone marrow mesenchymal stem cells (BM-MSCS) in thioacetamide induced liver fibrosis in rats

Homing and migration of bone marrow mesenchymal stem cells (BM-MSCs) to a target tissue has been ... more Homing and migration of bone marrow mesenchymal stem cells (BM-MSCs) to a target tissue has been a major concern because, only few cells reach the target tissue and remain there after systemic administration. The current study aimed at investigating the potential hepatoprotective role of claudin-4 in improving the homing and antifibrotic effect of BM-MSCs. In our study, Sprague-Dawley rats were randomly divided into six groups: Control group; Meloxicam group; Thioacetamide group; Thioacetamide + BM-MSCs group; Meloxicam + Thioacetamide group; Thioacetamide + Meloxicam + BM-MSCs. Flowcytometry, Western Blot, hematoxylin and eosin (H&E), Masson’s trichrome staining, immunohistochemical studies for the detection of α-Smooth muscle actin (α-SMA) and enzyme-linked immunosorbent assay (ELISA) were involved to measure different parameters. Results showed that in vivo BM-MSCs administration significantly improved histopathological changes and attenuated the elevated liver enzymes, lipid per...