Attalla F. El‐kott

King Khalid University

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Kareem Morsy

Cairo University

Sally Negm

King Khalid University

Bikash Karmakar

Presidency University

Ayman El-Meghawry El-Kenawy

Taif University

Refaat A. Eid

King Khalid University

Ali A. Shati

King Khalid University

Mohamed M. Abdel‐Daim

King Saud University

Mohamed Samir Ahmed Zaki

King Khalid University

Mohammed A. AlShehri

King Khalid University

Mashael Mohammed Bin-Meferij

Princess Nourah bint Abdulrahman University

Cooperative Institutions

King Khalid University

125

Mansoura University

Cairo University

Chinese Academy of Sciences

King Saud University

Alexandria University

Zagazig University

Delta University for Science and Technology

Ain Shams University

King Abdulaziz University

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Echinops Asteraceae extract guards against malathion-induced liver damage via minimizing oxidative stress, inflammation, and apoptosis.

Toxicon (2024)

Refaat A. Eid Mohammed Abadi Alsaleem Mansour A. Alghamdi Attalla F. El‐kott Gamal A. Mohamed

Malondialdehyde

10.1016/j.toxicon.2024.107750

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Citations (0)

Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis In Vitro and In Silico Studies

Current Medicinal Chemistry (2024)

Urwa Khalid Noor Fatima Naeem Ullah Sobia Ahsan Halim Ajmal Khan

Introduction: Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential. Method: This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP. The hydrazones (5a-o), reported as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated in vitro POP inhibition with IC50 values ranging from 13.60 ± 2.51 to 36.51 ± 1.82 μM. The derivative 5h, with an IC50 of 13.60 ± 2.51 μM, emerged as the most potent inhibitor. Results: Moreover, the in vitro kinetic study of compound 5h indicated that it exhibited concentration-dependent type of inhibition. in silico docking studies of 5h revealed robust interactions in the POP enzyme's active site, yielding a docking score of ˗6.30 Kcal/- mol, consistent with experimental results. Conclusion: All findings underscored the potential of synthesized derivatives for drug development.

Oligopeptidase

Morpholine

Druggability

Docking (animal)

IC50

ADME

10.2174/0109298673304532240911070202

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Prognostic Relevance of Concordant Expression CD69 and CD56 in Response to Bortezomib Combination Therapy in Multiple Myeloma Patients

Cancer Investigation (2021)

Nadia El‐Menshawy Nora A. Farag Doaa Atia Nashwa Abousamra Doaa Shahin

Multiple myeloma is an incurable hematological malignancy. Currently, the use of proteasome inhibitors could be superior to chemotherapy-based regimen in the treatment of this disease. However, resistance to bortezomib combination therapy still occurs in some patients. So, this research work aims to assess CD69 and CD56 expression in these cases and their relation to the response to therapy.Immunophenotyping by 4-color multi-parameter flow cytometry was carried out on 98 multiple myeloma cases. Clonal plasma cells were gated by co-expression of CD38 with CD138 with low SSC, negative or dim CD45.Double negative CD69 and CD56 (47.9%) multiple myeloma cases were associated with high serum β2 microglobulin, creatinine, calcium and low serum albumin. There was also a significant correlation between the absence of these markers with osteolytic lesions and unfavorable cytogenetic t (4;14) (p < 0.001). Moreover, there was a highly significant correlation between CD69- and CD56- with non-response to bortezomib combination therapy in multiple myeloma patients (p < 0.0001). Regression analysis for the prediction of non- response to treatment in these cases using different prognostic indicators revealed that high serum β2 microglobulin, unfavorable cytogenetic, advanced stage, and low expression of CD69 and CD56 were poor predictors of non-response.CD69 in association with CD56 could be an independent prognostic factor in multiple myeloma cases. It could be used in the routine laboratory assessment for refining stratification and timely therapeutic decision for highly cost therapy in developing countries.

Combination therapy

10.1080/07357907.2021.1964521

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Citations (7)

Acylated ghrelin protects aorta damage post-MI via activation of eNOS and inhibition of angiotensin-converting enzyme induced activation of NAD(P)H-dependent oxidase

Ultrastructural Pathology (2018)

Refaat A. Eid Attalla F. El‐kott Mohamed Samir Ahmed Zaki Muhammad Alaa Eldeen Fahaid Al‐Hashem

NAD(P)H dependent oxidase derived-reactive oxygen species (ROS) due to activation of the renin-angiotensin-aldosterone system (RAAS) in blood vessels postmyocardial infarction MI or during the HF leads to endothelium dysfunction and enhanced apoptosis. Acylated ghrelin (AG) is a well-reported cardioprotective and antiapoptotic agent for the heart. AG receptors are widely distributed in most of blood vessels, suggesting a role in the regulation of endothelial function and survival. This study investigated if AG can protect aorta of rats' postmyocardial infarction (MI)-induced damage and endothelial dysfunction. Adult male rats were divided into four groups of (1) Sham, (2) Sham + AG, (3) MI, and (4) MI + AG. Vehicle (normal saline) or AG (100 µ/kg) was administered to rats for 21 consecutive days, after which, numerous biochemical markers were detected by blot. Both histological and electron microscope studies were carried on aortic samples from MI-induced rats. AG increased protein levels of both total and phosphorylated forms of endothelial nitric oxide synthase (eNOS and p-eNOS, respectively). Only in MI-treated rats, AG prevented the decreases in the levels of reduced glutathione (GSH) and superoxide dismutase (SOD) and lowered levels of malondialdehyde (MDA) and glutathione disulfide (GSSG). Concomitantly, it lowered the increased protein levels of angiotensin-converting enzyme (ACE), p22phox and cleaved caspase-3 and prevented the aorta histological and ultrustructural abnormalities induced by MI.

Malondialdehyde

Endothelial Dysfunction

NAD(P)H oxidase

10.1080/01913123.2018.1526242

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Luteolin Alleviates AflatoxinB1-Induced Apoptosis and Oxidative Stress in the Liver of Mice through Activation of Nrf2 Signaling Pathway

Antioxidants (2021)

Shahid Ali Rajput Aftab Shaukat Kuntan Wu Imran Rashid Rajput Dost Muhammad Baloch

Aflatoxin B1 (AFB1), a threatening mycotoxin, usually provokes oxidative stress and causes hepatotoxicity in animals and humans. Luteolin (LUTN), well-known as an active phytochemical agent, acts as a strong antioxidant. This research was designed to investigate whether LUTN exerts protective effects against AFB1-induced hepatotoxicity and explore the possible molecular mechanism in mice. A total of forty-eight mice were randomly allocated following four treatment groups (n = 12): Group 1, physiological saline (CON). Group 2, treated with 0.75 mg/kg BW aflatoxin B1 (AFB1). Group 3, treated with 50 mg/kg BW luteolin (LUTN), and Group 4, treated with 0.75 mg/kg BW aflatoxin B1 + 50 mg/kg BW luteolin (AFB1 + LUTN). Our findings revealed that LUTN treatment significantly alleviated growth retardation and rescued liver injury by relieving the pathological and serum biochemical alterations (ALT, AST, ALP, and GGT) under AFB1 exposure. LUTN ameliorated AFB1-induced oxidative stress by scavenging ROS and MDA accumulation and boosting the capacity of the antioxidant enzyme (CAT, T-SOD, GSH-Px and T-AOC). Moreover, LUTN treatment considerably attenuates the AFB1-induced apoptosis in mouse liver, as demonstrated by declined apoptotic cells percentage, decreased Bax, Cyt-c, caspase-3 and caspase-9 transcription and protein with increased Bcl-2 expression. Notably, administration of LUTN up-regulated the Nrf2 and its associated downstream molecules (HO-1, NQO1, GCLC, SOD1) at mRNA and protein levels under AFB1 exposure. Our results indicated that LUTN effectively alleviated AFB1-induced liver injury, and the underlying mechanisms were associated with the activation of the Nrf2 signaling pathway. Taken together, LUTN may serve as a potential mitigator against AFB1-induced liver injury and could be helpful for the development of novel treatment to combat liver diseases in humans and/or animals.

10.3390/antiox10081268

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Citations (70)

Prognostic value of p53 and MDM2 Expression in Bilharziasis-Associated Squamous Cell Carcinoma of the Urinary Bladder

The International Journal of Biological Markers (2003)

Ayman El-Meghawry El-Kenawy Attalla F. El‐kott Abdalla Khalil

The aim of this study was to elucidate the associations between immunostaining for MDM2 and p53, their respective expression in squamous cell carcinoma of the urinary bladder, and the value of these variables for predicting treatment outcome after cystectomy. Inactivation of TP53 might play a role in the development and progression of bladder cancer. Complex formation with the MDM2 product is one mechanism that inactivates the p53 protein. Therefore, the MDM2 and the p53 protein were investigated to study potential interactions in bladder cancer. Fifty archival bladder tissue specimens were immunohistochemically stained using monoclonal antibodies against p53 and MDM2. Staining for p53 was observed in 48% of the specimens and staining for MDM2 in 20%. Univariate analysis demonstrated a significant correlation between p53 accumulation and survival (p = 0.0101), while the correlation between MDM2 and survival was not significant (p = 0.7183). The combined expression of MDM2 and p53 doest not add to the prognostic information provided by p53 alone.

Immunostaining

Univariate analysis

10.1177/172460080301800406

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Citations (8)

Green preparation of copper nanoparticle-loaded chitosan/alginate bio-composite: Investigation of its cytotoxicity, antioxidant and anti-human breast cancer properties

Arabian Journal of Chemistry (2021)

Dong Xu Enmiao Li Bikash Karmakar Nasser S. Awwad Hala A. Ibrahium

In this study, an eco-friendly and low-cost procedure for the in situ fabrication of Cu nanoparticles by using chitosan/alginate hydrogel. The prepared Cu [email protected]/Alg nanocomposite were characterized by advanced physicochemical techniques like Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX) and X-ray Diffraction (XRD) study. It has been established that chitosan/alginate-capped gold nanoparticles have a spherical shape with a mean diameter from 10 to 20 nm. In the cellular and molecular part of the recent study, the treated cells with Cu [email protected]/Alg nanocomposite were assessed by MTT assay for 48 h about the cytotoxicity and anti-human breast cancer properties on normal (HUVEC) and breast cancer cell lines i.e. infiltrating lobular carcinoma of breast (UACC-3133), inflammatory carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453). In the antioxidant test, the IC50 of Cu [email protected]/Alg nanocomposite and BHT against DPPH free radicals were 344 and 193 µg/mL, respectively. The IC50 of Cu [email protected]/Alg nanocomposite were 297, 386, and 359 µg/mL against KYSE-270, OE33, and ESO26 cell lines, respectively. The viability of malignant breast cell line reduced dose-dependently in the presence of Cu [email protected]/Alg nanocomposite.

MTT assay

10.1016/j.arabjc.2021.103638

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Citations (27)

Effects of Electromagnetic Radiation Produced by Mobile Phone on Some Visceral Organs of Rat

Journal of Medical Sciences(Faisalabad) (2011)

Abu Bakr El-Bediwi Attalla F. El‐kott Mohamed Saad Eman Eid

Mobile phone

10.3923/jms.2011.256.260

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Citations (16)

Green Nanoarchitectonics of Cu/Fe3O4 Nanoparticles Using Helleborus niger Extract Towards an Efficient Nanocatalyst, Antioxidant and Anti-lung Cancer Agent

Journal of Inorganic and Organometallic Polymers and Materials (2022)

Xue Yang Bikash Karmakar Huda Salem AlSalem Mona Saad Binkadem Soha T. Al‐Goul

MTT assay

10.1007/s10904-022-02430-w

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Citations (14)

Panax ginseng leaf aqueous extract mediated green synthesis of AgNPs under ultrasound condition and investigation of its anti-lung adenocarcinoma effects

Open Chemistry (2023)

Jingli Ni Sally Negm Attalla F. El‐kott Heba I. Ghamry Bikash Karmakar

Abstract Panax ginseng has many therapeutic uses in medicine. In the recent research, silver nanoparticles (AgNPs) were formulated by the Panax ginseng aqueous extract. The synthesized AgNPs’ characterization was analyzed using UV-Vis spectrophotometry, energy dispersive X-ray spectroscopy, scanning electron microscopy, fourier transformed infrared spectroscopy, transmission electron microscopy, and elemental mapping. The AgNPs were analyzed for their surface morphology by SEM. The successful synthesis of AgNPs was evident with TEM images. The AgNPs had a uniform distribution and homogenous spherical shaped morphology with mean diameter in the range of 20–30 nm. The cytotoxic and anti-lung adenocarcinoma ‎potentials of biologically formulated AgNPs‎ against NCI-H1563‎, NCI-H1437‎, NCI-H1299‎, and NCI-H2126 cells were determined. The anti-lung adenocarcinoma ‎ properties of the AgNPs ‎ removed NCI-H1563‎, NCI-H1437‎, NCI-H1299‎, and NCI-H2126 cells. The AgNPs’ IC 50 ‎ were 193, 156, 250, and 278 µg/mL against NCI-H1563‎, NCI-H1437‎, NCI-H1299‎, and NCI-H2126 cells, respectively. Also, AgNPs presented high antioxidant potential.

Silver nanoparticle

10.1515/chem-2023-0103

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Citations (3)