Publications by authors named "Ibrahim M Ibrahim"

43 Publications

Unifying the diagnosis of gestational diabetes mellitus: Introducing the NPRP criteria.

Prim Care Diabetes 2021 Aug 18. Epub 2021 Aug 18.

Mater Research and The University of Queensland, Brisbane, Queensland, Australia.

Aims: Disagreement about the appropriate criteria for the diagnosis of gestational diabetes mellitus (GDM) persists. This study examines an alternative approach which combines information from all time-points on the glucose tolerance test (GTT) into a single index and expands the GDM spectrum into four categories using data from three geographically and ethnically distinct populations.

Methods: A retrospective observational study design was used. Data from Wisconsin, USA (723 women) was used in derivation of the criterion and data from Doha, Qatar (1284 women) and Cape Town, South Africa (220 women) for confirmation. Pregnant women without pre-existing diabetes with a GTT done between 23 and 30 weeks gestation were included. A novel index was derived from the GTT termed the weighted average glucose (wAG). This was categorized into four pre-defined groups (henceforth National Priorities Research Program (NPRP) criterion); i) normal gestational glycemia (NGG), ii) impaired gestational glycemia (IGG), iii) GDM and iv) high risk GDM (hGDM).

Results: In the Doha cohort, compared to the NGG group, the odds of large for gestational age babies increased 1.33 fold (P = 0.432), 2.86 fold (P < 0.001) and 3.35 fold (P < 0.001) in the IGG, GDM and hGDM groups respectively. The odds of pregnancy induced hypertension increased 2.10 fold (P = 0.024) in GDM & hGDM groups compared to the IGG and NGG groups. In the Cape Town cohort, a third of women in the GDM group and two-thirds in the hGDM group progressed to T2DM at 5 years.

Conclusions: The NPRP categorization identifies four distinct risk clusters of glycemia in pregnancy which may aid better decision making in routine management, avoid potential over-diagnosis of women at lower risk of complications and assist with diabetes prevention in women at high-risk after an index pregnancy with GDM.
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http://dx.doi.org/10.1016/j.pcd.2021.08.006DOI Listing
August 2021

Amyloid β fibrils disruption by kolaviron: Molecular docking and extended molecular dynamics simulation studies.

Comput Biol Chem 2021 Oct 5;94:107557. Epub 2021 Aug 5.

Department of Biophysics, Faculty of Sciences, Cairo University, Giza, Egypt.

Garcinia kola (GK) produces notable effects against neurodegenerative conditions, including experimentally-induced Alzheimer's disease (AD). These remarkable effects are basically attributable to kolaviron (KV), a bioflavonoid constituent of this seed. Specifically, it has been reported that in AD models, KV produces interesting neuroprotective effects, being able to diminish associated neurotoxicity, via modulation of antioxidative, inflammatory and other disease modifying processes. Intriguingly, the effect of KV on amyloid-beta (Aβ) aggregation and disruption of preformed Aβ fibrils have not been studied. In this study, we have described a thorough computational study on the mechanism of action of KV as an Aβ fibrils disruptor at molecular level. We used comprehensive in silico docking evaluations and extended molecular dynamics simulation to mimic KV/Aβ fibrils system. Results indicate that KV was able to move within the Aβ fibrils, binding with important residues and components in the Aβ peptide identified to be vital for stabilizing preformed fibrils. KV destabilized the assembled Aβ fibrils, indicating the ability KV as a potential anti-amyloidogenic agent. Furthermore, this work highlighted the possibility of identifying new multifunctional phytocompounds as potent AD drugs.
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http://dx.doi.org/10.1016/j.compbiolchem.2021.107557DOI Listing
October 2021

SARS-CoV-2 host cell entry: an in silico investigation of potential inhibitory roles of terpenoids.

J Genet Eng Biotechnol 2021 Aug 5;19(1):113. Epub 2021 Aug 5.

Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria.

Background: Targeting viral cell entry proteins is an emerging therapeutic strategy for inhibiting the first stage of SARS-CoV-2 infection. In this study, 106 bioactive terpenoids from African medicinal plants were screened through molecular docking analysis against human angiotensin-converting enzyme 2 (hACE2), human transmembrane protease serine 2 (TMPRSS2), and the spike (S) proteins of SARS-CoV-2, SARS-CoV, and MERS-CoV. In silico absorption-distribution-metabolism-excretion-toxicity (ADMET) and drug-likeness prediction, molecular dynamics (MD) simulation, binding free energy calculations, and clustering analysis of MD simulation trajectories were performed on the top docked terpenoids to respective protein targets.

Results: The results revealed eight terpenoids with high binding tendencies to the catalytic residues of different targets. Two pentacyclic terpenoids (24-methylene cycloartenol and isoiguesteri) interacted with the hACE2 binding hotspots for the SARS-CoV-2 spike protein, while the abietane diterpenes were found accommodated within the S1-specificity pocket, interacting strongly with the active site residues TMPRSS2. 3-benzoylhosloppone and cucurbitacin interacted with the RBD and S2 subunit of SARS-CoV-2 spike protein respectively. These interactions were preserved in a simulated dynamic environment, thereby, demonstrating high structural stability. The MM-GBSA binding free energy calculations corroborated the docking interactions. The top docked terpenoids showed favorable drug-likeness and ADMET properties over a wide range of molecular descriptors.

Conclusion: The identified terpenoids from this study provides core structure that can be exploited for further lead optimization to design drugs against SARS-CoV-2 cell-mediated entry proteins. They are therefore recommended for further in vitro and in vivo studies towards developing entry inhibitors against the ongoing COVID-19 pandemic.
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http://dx.doi.org/10.1186/s43141-021-00209-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339396PMC
August 2021

Structure-based virtual screening suggests inhibitors of 3-Chymotrypsin-Like Protease of SARS-CoV-2 from Vernonia amygdalina and Occinum gratissimum.

Comput Biol Med 2021 09 21;136:104671. Epub 2021 Jul 21.

Human Nutraceuticals and Bioinformatics Research Unit, Department of Biochemistry, Salem University, Nigeria.

Antiviral culinary plants are potential bioresources for preventive nutraceuticals and/or antiviral drugs in COVID-19. Structure-based virtual screening was undertaken to screen 173 compounds previously reported from Vernonia amygdalina and Occinum gratissimum for direct interaction with the active site of the 3-Chymotrypsin-Like Protease (3CL) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on docking scores and comparison with reference inhibitors, a hit-list of 10 top phytocompounds was defined, which also had strong interactions with the catalytic centre of 3CL from three related strains of coronavirus (SARS-CoV, MERS-CoV, HKU4). Among these, six compounds (neoandrographolide, vernolide, isorhamnetin, chicoric acid, luteolin, and myricetin) exhibited the highest binding tendencies to the equilibrated conformers of SARS-CoV-2 3CL in an in-depth docking analysis to 5 different representative conformations from the cluster analysis of the molecular dynamics simulation (MDS) trajectories of the protein. In silico drug-likeness analyses revealed two drug-like terpenoids viz: neoandrographolide and vernolide as promising inhibitors of SARS-CoV-2 3CL. These structures were accommodated within the substrate-binding pocket; and interacted with the catalytic dyad (Cys and His), the oxyanion loop (residues 138-145), and the S1/S2 sub-sites of the enzyme active site through the formation of an array of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulation and binding free energy calculation revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability. Therefore, these compounds may stabilize the conformation of the flexible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during the proteolytic activity of the enzyme.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294106PMC
September 2021

Novel adenosine derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective.

Pharmacol Rep 2021 Jun 24. Epub 2021 Jun 24.

Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt.

Background: SARS-CoV-2 is a newly emerged human coronavirus that severely affected human health and the economy. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target to stop virus replication. The adenosine derivative, remdesivir, was authorized for emergency use 10 months ago by the United States FDA against COVID-19 despite its doubtful efficacy against SARS-CoV-2.

Methods: A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work.

Results: The results reveal a better binding affinity of 11 modifications compared to remdesivir. Compounds 8, 9, 10, and 11 show the best binding affinities against SARS-CoV-2 RdRp conformations gathered during 100 ns of the Molecular Dynamics Simulation (MDS) run (- 8.13 ± 0.45 kcal/mol, - 8.09 ± 0.67 kcal/mol, - 8.09 ± 0.64 kcal/mol, and - 8.07 ± 0.73 kcal/mol, respectively).

Conclusions: The present study suggests these four compounds as potential SARS-CoV-2 RdRp inhibitors, which need to be validated experimentally.
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http://dx.doi.org/10.1007/s43440-021-00300-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222949PMC
June 2021

Recognition through GRP78 is enhanced in the UK, South African, and Brazilian variants of SARS-CoV-2; An in silico perspective.

Biochem Biophys Res Commun 2021 07 21;562:89-93. Epub 2021 May 21.

Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.

New SARS-CoV-2 variants emerged in the United Kingdom and South Africa in December 2020 in concomitant with the Brazillian variant in February 2021 (B.1.1.248 lineage) and currently sparking worldwide during the last few months. The new strain 501.V2 in South Africa bears three mutations in the spike receptor-binding domain (RBD); K417 N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage has 12 mutations. In the current study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wild-type and mutated isoforms. Additionally, the cell-surface Glucose Regulated Protein 78 (CS-GRP78) associated with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-S RBD) is modeled at the presence of these mutant variants of the viral spike. The results showed that E484K and N501Y are critical in viral spike recognition through either ACE2 or CS-GRP78. The mutated variants (the UK, South African, and Brazilian) of the spike RBD tightly bind to GRP78 more than in the case of the wild-type RBD. These results point to the potent role of GRP78 with ACE2 in the attachment of the new variants, which could be a key for the design of inhibitors to block SARS-CoV-2 attachment and entry to the host cell.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139235PMC
July 2021

COVID-19 and Cell Stress.

Adv Exp Med Biol 2021 ;1318:169-178

Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.

The present century will undoubtedly be marked with the COVID-19 global health crisis. It is not time yet to talk about the total number of deaths and hospitalizations, as they are enormously growing daily. Understanding the nature of COVID-19-induced pneumonia is vital in order to deal with the associated health complications. Cell stress is an established mechanism known to be associated with infection and cancer. Different proteins crucial for cellular response to stress are reported to be a possible target to stop the infection and to reduce the chemo-resistance in cancer. Heat shock protein (HSP) families of chaperones play an essential role in cells both in normal state and under stress. The upregulation of HSP5A, also termed GRP78 or Bip, is reported in different viral infections. This chapter introduces the current knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the COVID-19 pandemic, and cell stress aimed at defining possible strategies to combat the COVID-19 pandemic.
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http://dx.doi.org/10.1007/978-3-030-63761-3_10DOI Listing
May 2021

A Hyaluronic Acid Functionalized Self-Nano-Emulsifying Drug Delivery System (SNEDDS) for Enhancement in Ciprofloxacin Targeted Delivery against Intracellular Infection.

Nanomaterials (Basel) 2021 Apr 22;11(5). Epub 2021 Apr 22.

Department of Chemistry, College of Natural Science, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Gyeongbuk, Korea.

Ciprofloxacin (CIP), a potent anti-bacterial agent of the fluroquinolone family, shows poor solubility and permeability, thus leading to the development of intracellular pathogens induced multi-drug resistance and biofilms formation. To synergistically improve the biopharmaceutical parameters of CIP, a hyaluronic acid (FDA approved biocompatible polymer) functionalized self-nano emulsifying drug delivery system (HA-CIP-SNEDDS) was designed in the present study. SNEDDS formulations were tested via solubility, droplet size, zeta potential, a polydispersity index, thermodynamic stability, surface morphology, solid-state characterization, drug loading/release, cellular uptake, and biocompatibility. The final (HA-CIP-SNEDDS) formulation exhibited a mean droplet size of 50 nm with the 0.3 poly dispersity index and negative zeta potential (-11.4 mV). HA-based SNEDDS containing CIP showed an improved ability to permeate goat intestinal mucus. After 4 h, CIP-SNEDDS showed a 2-fold and HA-CIP-SNEDDS showed a 4-fold permeation enhancement as compared to the free CIP. Moreover, 80% drug release of HA-CIP-SNEDDS was demonstrated to be superior and sustained for 72 h in comparison to free CIP. However, anti-biofilm activity of HA-CIP-SNEDDS against was higher than CIP-SNEDDS and free CIP. HA-CIP-SNEDDS exhibited increased biocompatibility and improved oral pharmacokinetics as compared to free CIP. Taken together, HA-CIP-SNEDDS formulation seems to be a promising agent against with a strong targeting potential.
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http://dx.doi.org/10.3390/nano11051086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146397PMC
April 2021

Dual targeting of cytokine storm and viral replication in COVID-19 by plant-derived steroidal pregnanes: An in silico perspective.

Comput Biol Med 2021 07 18;134:104406. Epub 2021 Apr 18.

Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria.

The high morbidity and mortality rate of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection arises majorly from the Acute Respiratory Distress Syndrome and "cytokine storm" syndrome, which is sustained by an aberrant systemic inflammatory response and elevated pro-inflammatory cytokines. Thus, phytocompounds with broad-spectrum anti-inflammatory activity that target multiple SARS-CoV-2 proteins will enhance the development of effective drugs against the disease. In this study, an in-house library of 117 steroidal plant-derived pregnanes (PDPs) was docked in the active regions of human glucocorticoid receptors (hGRs) in a comparative molecular docking analysis. Based on the minimal binding energy and a comparative dexamethasone binding mode analysis, a list of top twenty ranked PDPs docked in the agonist conformation of hGR, with binding energies ranging between -9.8 and -11.2 kcal/mol, was obtained and analyzed for possible interactions with the human Janus kinases 1 and Interleukins-6 and SARS-CoV-2 3-chymotrypsin-like protease, Papain-like protease and RNA-dependent RNA polymerase. For each target protein, the top three ranked PDPs were selected. Eight PDPs (bregenin, hirundigenin, anhydroholantogenin, atratogenin A, atratogenin B, glaucogenin A, glaucogenin C and glaucogenin D) with high binding tendencies to the catalytic residues of multiple targets were identified. A high degree of structural stability was observed from the 100 ns molecular dynamics simulation analyses of glaucogenin C and hirundigenin complexes of hGR. The selected top-eight ranked PDPs demonstrated high druggable potentials and favourable in silico ADMET properties. Thus, the therapeutic potentials of glaucogenin C and hirundigenin can be explored for further in vitro and in vivo studies.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053224PMC
July 2021

Pumpkin seed oil vs. minoxidil 5% topical foam for the treatment of female pattern hair loss: A randomized comparative trial.

J Cosmet Dermatol 2021 Sep 12;20(9):2867-2873. Epub 2021 Feb 12.

Department of Dermatology, National Research Centre, Cairo, Egypt.

Background: Pumpkin (Cucurbita pepo L.) is an annual climber plant, and its seeds have considerable amount of oil with nutritional and medicinal importance.

Aim: The present study aimed to investigate the clinical efficacy of pumpkin seed oil (PSO) in the treatment of female pattern hair loss (FPHL) and compare its effects with minoxidil 5% foam.

Methods: Patients with FPHL were randomly assigned to pumpkin seed oil (n = 30; group A) or minoxidil 5% foam (n = 30; group B) for a period of 3 months. Patients were evaluated clinically and dermoscopically at baseline, at one and half months, and at the end of the 3-month study.

Results: Among group A (pumpkin seed oil) candidates, a significant decrease was observed in hair shaft diversity before and after treatment (30.5 ± 6.2%, 24.0 ± 4.02, P < .001, respectively) as well as in the vellus hairs (22.5 ± 4.9, 15.8 ± 2.2, P < .001, respectively). Upright regrowing hairs significantly increased from (0.13 ± 0.5) before treatment to (0.9 ± 1.0) after treatment (P < .001). In group B (minoxidil applying) candidates, a significant decrease was observed in hair shaft diversity before and after treatment (31.5 ± 6.3%, 21.3 ± 2.2, P < .001, respectively) as well as in the vellus hairs (24.7 ± 6.4, 19.5 ± 5.4, P = .02, respectively). Conclusion Findings of the present trial provide evidence of a promising potential role of PSO in treating FPHL.
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http://dx.doi.org/10.1111/jocd.13976DOI Listing
September 2021

Host-cell recognition through GRP78 is enhanced in the new UK variant of SARS-CoV-2, in silico.

J Infect 2021 May 22;82(5):186-230. Epub 2021 Jan 22.

Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.

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http://dx.doi.org/10.1016/j.jinf.2021.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825984PMC
May 2021

Alkaloids and flavonoids from African phytochemicals as potential inhibitors of SARS-Cov-2 RNA-dependent RNA polymerase: an perspective.

Antivir Chem Chemother 2020 Jan-Dec;28:2040206620984076

Faculty of Sciences, Department of Biophysics Cairo University, Giza, Egypt.

Corona Virus Disease 2019 (COVID-19) is a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Exploiting the potentials of phytocompounds is an integral component of the international response to this pandemic. In this study, a virtual screening through molecular docking analysis was used to screen a total of 226 bioactive compounds from African herbs and medicinal plants for direct interactions with SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). From these, 36 phytocompounds with binding affinities higher than the approved reference drugs (remdesivir and sobosivir), were further docked targeting the active sites of SARS-CoV-2, as well as SARS-CoV and HCV RdRp. A hit list of 7 compounds alongside two positive controls (remdesivir and sofosbuvir) and two negative controls (cinnamaldehyde and Thymoquinone) were further docked into the active site of 8 different conformations of SARS-CoV-2 RdRp gotten from molecular dynamics simulation (MDS) system equilibration. The top docked compounds were further subjected to predictive druglikeness and ADME/tox filtering analyses. Drugable alkaloids (10'-hydroxyusambarensine, cryptospirolepine, strychnopentamine) and flavonoids (usararotenoid A, and 12α-epi-millettosin), were reported to exhibit strong affinity binding and interactions with key amino acid residues in the catalytic site, the divalent-cation-binding site, and the NTP entry channel in the active region of the RdRp enzyme as the positive controls. These phytochemicals, in addition to other promising antivirals such as remdesivir and sofosbuvir, may be exploited towards the development of a cocktail of anti-coronavirus treatments in COVID-19. Experimental studies are recommended to validate these study.
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http://dx.doi.org/10.1177/2040206620984076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783895PMC
January 2021

An Epidemiological Study on Orodental Disorders in 3,791 Working Donkeys in Egypt: Prevalence and Risk Factors.

J Equine Vet Sci 2020 12 8;95:103274. Epub 2020 Oct 8.

Department of Surgery, Anesthesiology & Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Orodental disorders are common in equidae and can lead to serious clinical complications. This study determines the prevalence rate (PR) of orodental disorders in working donkeys in Egypt and their potential risk factors. During 4 years, 3,791 donkeys were examined in six Egyptian governorates. Full case history and thorough clinical and oral examinations were performed. Radiography and oroendoscopy were undertaken whenever possible. All data were statistically analyzed using Poisson generalized linear models to compare PR among governorates, sex, years, body condition score, and age groups and to determine the potential risk factors. Of 3,791 examined donkeys, 954 donkeys (25.17%) had orodental disorders. The PRs of acquired disorders were 9.81% sharp enamel points, 5.86% buccal ulcers, 4.88% hook, 4.70% overgrown teeth, 4.19% periodontal disease, 3.11% ramp, 2.60% dental caries, 2.37% dental calculus, 2.30% diastema, 2.06% step mouth, 2.00% soft tissue injuries other than buccal ulcers, 1.77% worn tooth, 1.37% loose tooth, 1.29% exaggerated transverse ridge, 1.24% fractured teeth, 0.82% missing teeth, 0.69% wave mouth, 0.50% molar table angle change, and 0.45% wolf tooth overgrowth. The PRs of the congenital disorders were 1.90% displaced teeth, 1.37% deviated teeth, 0.58% retained teeth, 0.16% overbite, 0.16% underbite, 0.11% supernumerary teeth, and 0.11% premolar cap. The risk factors significantly associated (P < .05) with the orodental disorders were age and sex of the animal, geographic location, and year of examination. This study provides a database for future studies on orodental disorders and for designing effective preventive and therapeutic strategies for these disorders in donkeys.
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http://dx.doi.org/10.1016/j.jevs.2020.103274DOI Listing
December 2020

Prevention of SARS-CoV-2 cell entry: insight from interaction of drug-like alkaloids with spike glycoprotein, human ACE2, and TMPRSS2.

J Biomol Struct Dyn 2020 Oct 22:1-25. Epub 2020 Oct 22.

Department of Biological Sciences, KolaDaisi University, Ibadan, Nigeria.

COVID-19 is a respiratory disease caused by SARS-CoV-2, an enveloped positive sense RNA virus. The SARS-CoV-2 spike glycoprotein, angiotensin-converting enzyme 2 (ACE2) and human transmembrane protease serine 2 (TMPRSS2) are essential for the host cell-mediated viral entry. Targeting these proteins represent viable options to stop the first stage of infection and transmission. Hence, 97 alkaloids from African medicinal plants with reported antiviral activity were evaluated for this purpose via studies. These alkaloids were docked for their interactions with SARS-CoV-2 spike glycoprotein, ACE2, and TMPRSS2. Top 20 alkaloids with highest binding affinities were further screened for their interactions with spike glycoprotein of SARS-CoV and MERS-CoV, and with ACE2-SARS-CoV-2 receptor-binding domain complex (ACE2-RBD). The energy profiling, molecular dynamics simulation (MDS), binding free energy base on Molecular Mechanics/Generalized Born Surface Area (MMGBSA), clustering of MDS trajectories, and virtual physicochemical and pharmacokinetic screening of the best docked alkaloids were performed. Results revealed that more than 15 alkaloids interacted better than the reference compounds. 10-Hydroxyusambarensine and Cryptospirolepine were docked in a similar binding pattern to the S1-specificy pocket of TMPRSS2 as camostat (reference inhibitor). The strong binding affinities, stability of the alkaloid-protein complexes and amino acid interactions displayed by cryptospirolepine, 10-hydroxyusambarensine, and cryptoquindoline with important binding hotspots of the proteins suggest these alkaloids have the potential of altering the capacity of SARS-CoV-2 membrane mediated host cell entry. Further and evaluation of these "drug-like" alkaloids as potential inhibitors of coronavirus cell entry is proposed.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1835726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594191PMC
October 2020

Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19.

Phytomedicine 2021 May 22;85:153310. Epub 2020 Aug 22.

Biophysics Department, Faculty of Sciences, Cairo University, Giza, 12613, Egypt.

Background: SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic.

Purpose: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation.

Methods: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions.

Results: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 M, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes.

Conclusion: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models.
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http://dx.doi.org/10.1016/j.phymed.2020.153310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442560PMC
May 2021

A possible role for GRP78 in cross vaccination against COVID-19.

J Infect 2021 02 10;82(2):282-327. Epub 2020 Sep 10.

Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt; Department of physics, Faculty of Science, Islamic University in Madinah, KSA, Saudi Arabia.

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http://dx.doi.org/10.1016/j.jinf.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486427PMC
February 2021

Zika virus envelope - heat shock protein A5 (GRP78) binding site prediction.

J Biomol Struct Dyn 2021 Sep 24;39(14):5248-5260. Epub 2020 Jun 24.

Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt.

Recent studies reported the association of the Zika virus (ZIKV) with a stress response receptor on the host cell membrane that facilitates viral entry. This host receptor was the heat shock protein A5 (HSPA5), also termed glucose-regulating protein 78 (GRP78). In this study, structural bioinformatics and molecular dynamics simulations were utilized to suggest the binding site of ZIKV envelope protein during the interaction with cell-surface GRP78. The Pep42 cyclic peptide was used as a profiler, as it was reported earlier, to target GRP78 on the cancer cell membrane selectively. Sequence and structural alignments show that part of the ZIKV envelope protein (C308-C339 region), in addition to its cyclic nature, has somehow sequence and structural similarities to the cyclic Pep42. Three amino acids in the ZIKV envelope were identical to those in the Pep42 peptide. Cyclic peptides dynamics are studied, and its binding to GRP78 is predicted. Protein-protein docking is further performed to explore the binding characteristics of the ZIKV envelope to GRP78. Results revealed that the binding was favorable between ZIKV envelope protein and GRP78. The docking pose revealed the involvement of the substrate-binding domain ß of GRP78 and the domain III of the ZIKV envelope protein in viral recognition for the host-cell.
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http://dx.doi.org/10.1080/07391102.2020.1784794DOI Listing
September 2021

COVID-19 spike-host cell receptor GRP78 binding site prediction.

J Infect 2020 05 10;80(5):554-562. Epub 2020 Mar 10.

Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt; College of Applied Medical Sciences, University of Al-Jouf, Saudi Arabia. Electronic address:

Objectives: Understanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition.

Methods: In this study, the COVID-19 spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The COVID-19 spike protein is modeled using its counterpart, the SARS spike.

Results: Sequence and structural alignments show that four regions, in addition to its cyclic nature have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor.

Conclusions: We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues can be used to develop therapeutics specific against COVID-19.
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http://dx.doi.org/10.1016/j.jinf.2020.02.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102553PMC
May 2020

Bioremediation potential of a halophilic Halobacillus sp. strain, EG1HP4QL: exopolysaccharide production, crude oil degradation, and heavy metal tolerance.

Extremophiles 2020 Jan 7;24(1):157-166. Epub 2019 Nov 7.

Department of Agricultural Microbiology, Faculty of Agriculture, Fayoum University, Fayoum, 63514, Egypt.

A halophilic bacterial strain, EG1HP4QL, was isolated from a salt sample from Lake Qarun, Fayoum Province, Egypt. Morphological, physiological, biochemical, and phylogenetic analyses indicated that the strain belonged to the genus Halobacillus. Strain EG1HP4QL produced an extracellular polysaccharide (EPS), with production peaking (5.9 g L) during growth on medium S-G containing 2% (w/v) sucrose at 35 °C (pH 8.0). The EPS had significant emulsifying activity (E %) against kerosene (65.7 ± 0.8%), o-xylene (64.0 ± 1%), and sunflower oil (44.7 ± 0.5%). The composition of the EPS included two polymers-a negatively charged and a neutral one (~ 3:1)-in which mannose and glucose were the main neutral monosaccharide constituents. Strain EG1HP4QL was able to utilize crude oil (35.3%) as the sole carbon source within 12 days. The minimum inhibitory concentrations of heavy metals [Zn(II), Cd(II), Pb(II), Ni(II), and Cu(II)] for strain EG1HP4QL were 1.0, 2.0, 2.0, 2.5, and 5 mM, respectively.
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http://dx.doi.org/10.1007/s00792-019-01143-2DOI Listing
January 2020

A long acting nanoformulated lamivudine ProTide.

Biomaterials 2019 12 5;223:119476. Epub 2019 Sep 5.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address:

A long acting (LA) hydrophobic and lipophilic lamivudine (3TC) was created as a phosphoramidate pronucleotide (designated M23TC). M23TC improved intracellular delivery of active triphosphate metabolites and enhanced antiretroviral and pharmacokinetic (PK) profiles over the native drug. A single treatment of human monocyte derived macrophages (MDM) with nanoformulated M23TC (NM23TC) improved drug uptake, retention, intracellular 3TC triphosphates and antiretroviral activities in MDM and CD4 T cells. PK tests of NM23TC administered to Sprague Dawley rats demonstrated sustained prodrug and drug triphosphate levels in blood and tissues for 30 days. The development of NM23TC remains a substantive step forward in producing LA slow effective release antiretrovirals for future clinical translation.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945491PMC
December 2019

Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation.

Int J Nanomedicine 2019 7;14:6231-6247. Epub 2019 Aug 7.

Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.

Purpose: A palmitoylated prodrug of emtricitabine (FTC) was synthesized to extend the drug's half-life, antiretroviral activities and biodistribution.

Methods: A modified FTC prodrug (MFTC) was synthesized by palmitoyl chloride esterification. MFTC's chemical structure was evaluated by nuclear magnetic resonance. The created hydrophobic prodrug nanocrystals were encased into a poloxamer surfactant and the pharmacokinetics (PK), biodistribution and antiretroviral activities of the nanoformulation (NMFTC) were assessed. The conversion of MFTC to FTC triphosphates was evaluated.

Results: MFTC coated with poloxamer formed stable nanocrystals (NMFTC). NMFTC demonstrated an average particle size, polydispersity index and zeta potential of 350 nm, 0.24 and -20 mV, respectively. Drug encapsulation efficiency was 90%. NMFTC was readily taken up by human monocyte-derived macrophages yielding readily detected intracellular FTC triphosphates and an extended PK profile.

Conclusion: NMFTC shows improved antiretroviral activities over native FTC. This is coordinate with its extended apparent half-life. The work represents an incremental advance in the development of a long-acting FTC formulation.
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http://dx.doi.org/10.2147/IJN.S215447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689761PMC
November 2019

Synthesis of a long acting nanoformulated emtricitabine ProTide.

Biomaterials 2019 11 20;222:119441. Epub 2019 Aug 20.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address:

While antiretroviral therapy (ART) has revolutionized treatment and prevention of human immunodeficiency virus type one (HIV-1) infection, regimen adherence, viral mutations, drug toxicities and access stigma and fatigue are treatment limitations. These have led to new opportunities for the development of long acting (LA) ART including implantable devices and chemical drug modifications. Herein, medicinal and formulation chemistry were used to develop LA prodrug nanoformulations of emtricitabine (FTC). A potent lipophilic FTC phosphoramidate prodrug (M2FTC) was synthesized then encapsulated into a poloxamer surfactant (NM2FTC). These modifications extended the biology, apparent drug half-life and antiretroviral activities of the formulations. NM2FTC demonstrated a >30-fold increase in macrophage and CD4+ T cell drug uptake with efficient conversion to triphosphates (FTC-TP). Intracellular FTC-TP protected macrophages against an HIV-1 challenge for 30 days. A single intramuscular injection of NM2FTC, at 45 mg/kg native drug equivalents, into Sprague Dawley rats resulted in sustained prodrug levels in blood, liver, spleen and lymph nodes and FTC-TP in lymph node and spleen cells at one month. In contrast, native FTC-TPs was present for one day. These results are an advance in the transformation of FTC into a LA agent.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945494PMC
November 2019

GRP78: A cell's response to stress.

Life Sci 2019 Jun 9;226:156-163. Epub 2019 Apr 9.

Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt. Electronic address:

Background: Glucose-Regulated Protein 78 (GRP78) is a chaperone heat shock protein that has been intensely studied in the last two decades. GRP78 is the master of the unfolded protein response (UBR) in the Endoplasmic Reticulum (ER) in normal cells. GRP78 force the unfolded proteins to refold or degrade using cellular degradation mechanisms.

Scope: Under stress, the overexpression of GRP78 on the cell membrane mediates the vast amount of disordered proteins. Unfortunately, this makes it a tool for pathogens (bacterial, fungal and viral) to enter the cell and to start different pathways leading to pathogenesis. Additionally, GRP78 is overexpressed on the membranes of various cancer cells and increase the aggressiveness of the disease.

Major Conclusions: The current review summarizes structure, function, and different mechanisms GRP78 mediate in response to normal or stress conditions.

General Significance: GRP78 targeting and possible inhibition mechanisms are also covered in the present review aiming to prevent the virulence of pathogens and cancer.
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http://dx.doi.org/10.1016/j.lfs.2019.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094232PMC
June 2019

Effectiveness of intralesional vitamin D injection in the treatment of common warts: Single-blinded placebo-controlled study.

Dermatol Ther 2019 05 16;32(3):e12882. Epub 2019 Apr 16.

Department of Dermatology and Venereology Faculty of Medicine, Al- Azhar University, Cairo, Egypt.

Warts are common viral infection of the skin, usually treated with destructive methods like electrocautery, cryotherapy or laser ablation. Topical vitamin D has been used to treat warts with variable success is to evaluate the efficacy of intralesional vitamin D injection in the treatment of common warts. Fifty patients were divided into two groups: 30 patients as cases group who received intralesional injection of 0.2 mL of vitamin D (300,000 IU) into the base of mother wart for two sessions and another 20 patients as a control group who were injected with normal saline solution. Standardized photographs were taken before the procedure, and 1 month and 3 months after the procedure. The degree of the response was classified into complete, partial, and no response. Complete clearance of the target injected warts occurred in 40% of patients in cases group while it occurred only in 5% of patients in control group (p ≤ .001) that was statistically significant. Intralesional injection of vitamin D may be considered a good and safe modality for the treatment of common warts.
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http://dx.doi.org/10.1111/dth.12882DOI Listing
May 2019

Structure of the O-specific polysaccharide from a halophilic bacterium Halomonas ventosae RU5S2EL.

Carbohydr Res 2019 Feb 15;473:1-4. Epub 2018 Dec 15.

N. G. Chernyshevsky Saratov State University, 83 Ulitsa Astrakhanskaya, Saratov, 410012, Russia; Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, 13 Prospekt Entuziastov, Saratov, 410049, Russia.

Halomonas ventosae RU5S2EL, a halophilic Gram-negative bacterium isolated from salt sediments of lake Elton (Russia), was cultivated and the lipopolysaccharide was extracted by the Westphal procedure. The O-specific polysaccharide (OPS) was obtained by mild acid hydrolysis of the lipopolysaccharide and was studied by sugar analysis along with H and C NMR spectroscopy, including H,H COSY, TOCSY, ROESY, H,C HSQC, and HMBC experiments as well as Smith degradation. The OPS was found to consist of branched pentasaccharide repeating units of the following structure.
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http://dx.doi.org/10.1016/j.carres.2018.12.010DOI Listing
February 2019

Large Balloon Dilatation Versus Mechanical Lithotripsy After Endoscopic Sphincterotomy in the Management of Large Common Bile Duct Stones in Cirrhotic Patients: A Randomized Study.

J Clin Gastroenterol 2019 04;53(4):e150-e156

Gastroenterology Department, Al-Ahrar Teaching Hospital, Zagazig.

Background And Study Aim: Removal of large common bile duct (CBD) stones is one of the challenges faced during endoscopic retrograde cholangiopancreatography, and it seems more difficult in cirrhotic patients because of suspected higher rates of adverse events, especially bleeding diathesis. This study aimed at comparing the success rate and complications between mechanical lithotripsy (ML) and large balloon dilation (LBD) after endoscopic sphincterotomy in patients with liver cirrhosis.

Patients And Methods: Ninety-eight cirrhotic patients with calcular obstructive jaundice were included and randomly divided into 2 groups: group A comprising 49 patients treated by LBD and group B comprising 49 patients treated by ML. All patients underwent sphincterotomy initially. All patients were subjected to thorough history taking and complete clinical examination. Pancreatic enzyme concentrations were measured 4 hours before and 24 hours after the procedure, and complete blood cell count and liver function tests were performed before and the morning after the procedure. Before and during endoscopic retrograde cholangiopancreatography, stone size and number were verified.

Results: The success rate for CBD clearance was 98% and 93.8% for LBD and ML, respectively. The rate of adverse events in this study was 10.2% (10/98), and bleeding was the commonest reported complication (5/10). Group B developed more (16.3%) adverse events than group A (4.1%), and the difference was statistically significant (P=0.04).

Conclusion: Endoscopic sphincterotomy followed by LBD is a safe and effective treatment for large CBD stones in cirrhotic patients in comparison with sphincterotomy followed by ML.
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http://dx.doi.org/10.1097/MCG.0000000000001000DOI Listing
April 2019

Evaluation of topical liposome incorporated clove oil in the treatment of idiopathic palmar hyperhidrosis: Single-blinded placebo-controlled study.

J Cosmet Dermatol 2018 Dec 28;17(6):1084-1089. Epub 2017 Dec 28.

Department of Dermatology and Venerology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

Introduction: Palmar hyperhidrosis is of great concern to patients because of its physical, occupational, and psychological impact on quality of life. Topical clove oil has been used in many conditions due to its major component Eugenol that exerts blocking effect on nerve transmission.

Aim Of The Work: To assess the efficacy of topical liposome incorporated clove oil in decreasing the rate of sweating among patients with idiopathic palmar hyperhidrosis.

Patients And Method: Forty patients with palmar hyperhidrosis were treated with clove oil 45% in liposome and another twenty patients were treated as a control group with 0.9% saline solution and evaluation was carried out before and after treatment through gravimetry testing and hyperhidrosis disease severity scale (HDSS).

Result: The gravimetry testing among clove oil-treated group showed that the mean sweating rate before treatment was 80.5 ± 41.85 (SD) mg/min which decreased significantly after treatment to 52.98 ± 37.94(SD) mg/min (P value < .001). On the other hand, the placebo-treated group,(control) the mean sweating rate before treatment was 77.40 ± 29.29(SD) which did not show significant improvement after placebo application 77.35 ± 28.29(SD; P value = .957).

Conclusion: The topical application of 45% clove oil in liposome twice daily for 2 weeks showing promising result evidenced by declining in the rate of palmar sweating among patients with idiopathic palmar hyperhidrosis.
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http://dx.doi.org/10.1111/jocd.12471DOI Listing
December 2018

Effectiveness of topical clove oil on symptomatic treatment of chronic pruritus.

J Cosmet Dermatol 2017 Dec 5;16(4):508-511. Epub 2017 Apr 5.

Department of Dermatology, Al Azhar University, Cairo, Egypt.

Background: Pruritus is a frequent symptom in the general population and in many skin and systemic diseases. Its frequency demonstrates a high burden and an impaired quality of life.

Aim: Assessment of the efficacy of topically applied clove oil alone in the treatment of chronic pruritus.

Methods: Fifty selected subjects diagnosed with chronic pruritus due to either hepatic, renal, or diabetic causes were studied and divided into two groups of 25 patients each. Group I patients were instructed to hydrate the skin and then apply topical clove oil while group II patients applied petrolatum topically by hand; this application was done on the areas of pruritus, twice daily and for 2 weeks. The severity of the itch was assessed and compared before and after the study by 5-D itch scale. The results were analyzed by SPSS. Statistical methods such as descriptive analysis, independent-samples t-test, paired-samples t-test, and chi-square were employed.

Results: There was a significant improvement regarding all studied individual parameters (5-D itch scale) for the clove oil users with no significance among petrolatum users. Comparison of 5-D itch scale total score between patients of group I and patients of group II favored the improvement following the use of clove oil than using placebo (P value>.05).

Conclusion: The topical treatment of chronic pruritus with clove oils is effective, easy to use, safe, cheap, and more acceptable for whom topical and systemic treatments tend to be irritating, contraindicated, or less well tolerated.
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http://dx.doi.org/10.1111/jocd.12342DOI Listing
December 2017

Effectiveness of topical peppermint oil on symptomatic treatment of chronic pruritus.

Clin Cosmet Investig Dermatol 2016 11;9:333-338. Epub 2016 Oct 11.

Department of Dermatology, National Research Centre, Cairo, Egypt.

Background: Pruritus is one of the commonest skin complaints. Peppermint oil can be effective in reducing the severity of such a condition.

Aim: The aim of this study was to assess the efficacy of topically applied peppermint oil in the treatment of chronic pruritus.

Subjects And Methods: Fifty selected subjects diagnosed with chronic pruritus due to hepatic, renal, or diabetic cause were studied and divided into two groups of 25 patients each. Group I patients were instructed to hydrate the skin and then apply topical peppermint oil, while Group II patients applied petrolatum topically by hand; this application was done on the areas of pruritus, twice daily for 2 weeks. The severity of the itch was assessed and compared before and after the study by the 5-D itch scale (5D-IS). The results were analyzed by SPSS software. Statistical methods such as descriptive analysis, independent samples -test, paired samples -test, and chi-square test were employed.

Results: There was a significant improvement regarding all studied individual parameters (5-D IS) for the peppermint oil users with no significance among petrolatum users. A comparison of total score of 5-D IS between patients of Group I and patients of Group II favored the improvement following the use of peppermint oil than using placebo (-value <0.05).

Conclusion: The topical treatment of chronic pruritus with peppermint oil is effective, easy to use, safe, cheap, and more acceptable for those whose topical and systemic treatments tend to be irritating, contraindicated, or less well tolerated.
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http://dx.doi.org/10.2147/CCID.S116995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066694PMC
October 2016

Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis.

Int J Nanomedicine 2016;11:4849-4863. Epub 2016 Sep 22.

School of Chemistry and Biochemistry, Georgia Institute of Technology, and Laser Dynamics Laboratory, Atlanta, GA, USA; School of Chemistry, King Abdul Aziz University, Jeddah, Saudi Arabia.

Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment.
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http://dx.doi.org/10.2147/IJN.S109470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036785PMC
January 2017
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