Publications by authors named "Ahmed Sayed"

261 Publications

Green synthesis of AgNP-ligand complexes and their toxicological effects on Nilaparvata lugens.

J Nanobiotechnology 2021 Oct 13;19(1):318. Epub 2021 Oct 13.

Ministry of Agriculture, Key Laboratory of Molecular Biology of Crop Pathogens and Insect Pests, Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province, Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Yuhangtang Road 866, Hangzhou, Zhejiang, 310058, People's Republic of China.

Background: Despite developments in nanotechnology for use in the pharmaceutical field, there is still a need for implementation of this technology in agrochemistry. In this study, silver nanoparticles (AgNPs) were successfully prepared by a facile and an eco-friendly route using two different ligands, 2'-amino-1,1':4',1″-terphenyl-3,3″,5,5″-tetracarboxylic acid (HL) and 1,3,6,8-tetrakis (p-benzoic acid)-pyrene (TBAPy), as reducing agents. The physiochemical properties of the as-obtained AgNPs were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The toxicity of HL-AgNP and TBAPy-AgNP against the brown planthopper (BPH, Nilaparvata lugens) was also measured.

Results: SEM and TEM analyses demonstrated the formation of quasi-spherical AgNP structures in the presence of HL and TBAPy. Insecticidal assays showed that TBAPy is less effective against N. lugens, with a median lethal concentration (LC) of 810 mg/L, while the toxicity of HL increased and their LC reached 786 mg/L 168 h posttreatment at a high concentration of 2000 mg/L. HL-AgNPs were also highly toxic at a low concentration of 20 mg/L, with LC =  ~ 3.9 mg/L 168 h posttreatment, while TBAPy-AgNPs exhibited less toxicity at the same concentration, with LC =  ~ 4.6 mg/L.

Conclusions: These results suggest that the synthesized AgNPs using the two ligands may be a safe and cheaper method compared with chemical insecticides for protection of rice plants from pests and has potential as an effective insecticide in the N. lugens pest management program.
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http://dx.doi.org/10.1186/s12951-021-01068-zDOI Listing
October 2021

(doum)-derived extract alleviates hyperglycemia in diabetic rats: a comprehensive , and study.

Food Funct 2021 Oct 13. Epub 2021 Oct 13.

Department of Biochemistry, Faculty of Medicine, Minia University, Minia 61519, Egypt.

In the present study, we investigated the hypoglycemic effect of different extracts ( organic and aqueous) derived from the fruits of (doum) on male streptozotocin-induced diabetic rats. Blood glucose levels as well as the relative gene expression of insulin, TNF-α, and TGF-β were determined in the pancreatic tissue of the experimental animals. Treatment of STZ-induced diabetic rats with aqueous extracts of the plant fruit over 7 weeks significantly reduced the elevated blood glucose and increased the relative expression of insulin, while the relative expression of inflammatory mediators ( TNF-α and TGF-β) was significantly reduced. Histopathological investigation also revealed that the aqueous extract treatment effectively reversed the β-cell necrosis induced by STZ and restored its normal morphology. Furthermore, liquid chromatography high resolution mass spectrometry (LC-HRMS) and chemical investigation of the aqueous extract elucidated its major bioactive phytochemicals ( flavonoids) and putatively determined the pancreatic K channel as a target for these bioactive components. insulin secretion assay revealed that myricetin, luteolin, and apigenin were able to induce insulin secretion by human pancreatic cells (insulin production = 20.9 ± 1.3, 13.74 ± 1.8, and 11.33 ± 1.1 ng mL, respectively). Using molecular docking and dynamics simulations, we were able to shed the light on the insulin secretagogue's mode of action through these identified bioactive compounds and to determine the main structural elements required for its bioactivity. This comprehensive investigation of this native fruit will encourage future clinical studies to recommend edible and widely available fruits like doum to be a part of DM treatment plans.
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http://dx.doi.org/10.1039/d1fo02025kDOI Listing
October 2021

Effect of Stirrups on Plate End Debonding in Reinforced Concrete Beams Strengthened with Fiber Reinforced Polymers.

Polymers (Basel) 2021 Sep 28;13(19). Epub 2021 Sep 28.

Center of Excellence for Concrete Research and Testing, Department of Civil Engineering, College of Engineering, King Saud University, P.O. Box 800, Riyadh 11421, Saudi Arabia.

Plate end (PE) debonding is one of the critical debonding failure modes that may occur in reinforced concrete (RC) beams strengthened with externally bonded fiber reinforced polymers (FRPs). This study investigated the effect of internal steel stirrups on the PE debonding failure load of FRP-strengthened RC beams. The dimensions of the beams were 3400 × 400 × 200 mm. The beams were strengthened with carbon FRP (CFRP) sheets bonded to the soffit of the beams. The beams were divided into two series based on the distance of the cutoff point of the CFRP sheets from the nearest support. This distance was 50 mm or 300 mm, and the amount of steel stirrups was varied in terms of varying the stirrup diameter and spacing. The beams were simply supported and tested under four-point bending. The test results indicate that the effect of stirrups on the load carrying capacity of the beams was more pronounced for the beams with CFRP sheets extended close to the supports. It was also indicated that beams with larger amounts of stirrups failed in PE debonding by concrete cover separation while beams with lower amounts of stirrups failed in PE by either PE interfacial debonding or critical diagonal crack-induced debonding. The beams were analyzed using several analytical models from design guidelines and the literature. The result of analysis indicates that most of the available models failed to reflect the effect of stirrups in predicting PE debonding failure load of the beams. On the other hand, the models of El-Sayed et al. and Teng and Yao were able to capture such an effect with the best predictions provided by El-Sayed et al. model.
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http://dx.doi.org/10.3390/polym13193322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512576PMC
September 2021

Telomerase activator-65 and pomegranate peel improved the health status of the liver in aged rats; multi-targets involved.

Iran J Basic Med Sci 2021 Jun;24(6):842-850

Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt. 11566.

Objectives: This study was undertaken to investigate the efficacy of telomerase activator-65 (Ta-65) and pomegranate peel against aging-induced deteriorations in the liver.

Materials And Methods: The rats were divided into four groups: control, aged, aged rats treated with Ta-65, and pomegranate orally for two months.

Results: Aging significantly increased the serum levels of total protein, globulins, and protein carbonyl and reduced the insulin-like growth factor 1 (IGF-1). It also elevated the hepatic malondialdehyde and decreased the hepatic glutathione S-transferase (GST) activity. Aging elevated the expression of thioredoxin reductase1, telomerase reverse transcriptase, and cytochrome 3a1 in the liver; it increased the p53 protein level and elevated the activity of caspase-3 in the liver indicating the occurrence of apoptosis. The architecture of the liver deteriorated in the aged rats, as shown by both light and electron microscopy examinations. The liver of the aged rats had many apoptotic hepatocytes with shrunken nuclei. Many hepatocytes had dilated rough endoplasmic reticulum, many lysosomes, and many fat droplets. Administration of Ta-65 and pomegranate to the aged rats normalized most of the previous biochemical parameters and improved the liver architecture.

Conclusion: Ta-65 and pomegranate have anti-aging activity through targeting multiple cellular pathways. It is also noteworthy that Ta-65 was superior to pomegranate in its alleviative effects.
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http://dx.doi.org/10.22038/ijbms.2021.56670.12655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487600PMC
June 2021

Fabrication and Application of Zeolite/Acanthophora Spicifera Nanoporous Composite for Adsorption of Congo Red Dye from Wastewater.

Nanomaterials (Basel) 2021 Sep 19;11(9). Epub 2021 Sep 19.

Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt.

Systematic investigations involving laboratory, analytical, and field trials were carried out to obtain the most efficient adsorbent for the removal of congo red (CR) dye from industrial effluent. Modification of the zeolite (Z) by the Acanthophora Spicifera algae (AS; marine algae) was evaluated in terms of adsorption capability of the zeolite to remove CR dye from aqueous solution. The zeolite/algae composite (ZAS) was fabricated using the wet impregnation technique. The AS, Z, and the synthesized ZAS composite were analyzed utilizing various characterization techniques. The newly synthesized ZAS composite has an adsorption capacity that is significantly higher than that of Z and AS, particularly at low CR concentrations. Batch experiments were carried out to explore the effects of different experimental factors, as well as the dye adsorption isotherms and kinetics. Owing to the presence of intermolecular interactions, the computational analysis showed that the adsorption of the CR molecule on zeolite surfaces is exothermic, energetically favorable, and spontaneous. Furthermore, growing the zeolite surface area has no discernible effect on the adsorption energies in all configurations. The ZAS composite may be used as a low-cost substitute adsorbent for the removal of anionic dyes from industrial wastewater at lower dye concentrations, according to the experimental results. Adsorption of CR dye onto Z, AS, and ZAS adsorbents was adequately explained by pseudo-second-order kinetics and the Langmuir isotherm. The sorption mechanism was also evaluated using Weber's intra-particle diffusion module. Finally, field testing revealed that the newly synthesized adsorbent was 98.0% efficient at extracting dyes from industrial wastewater, proving the foundation of modern eco-friendly materials that aid in the reuse of industrial wastewater.
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http://dx.doi.org/10.3390/nano11092441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464800PMC
September 2021

Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 M Inhibitors from TDPEF34.

Biomolecules 2021 Sep 15;11(9). Epub 2021 Sep 15.

School of Computing, Engineering & Physical Science, University of the West of Scotland, Paisley PA1 2BE, UK.

SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease M in vitro. The extract of , TDPEF34, showed potential inhibition and was further analysed to identify potential M inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 M were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds (isolated as two conformers of S- and R-isomers), , and were found to have promising in vitro inhibitory activity towards M, with an IC values range of 0.36-0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent M inhibitors.
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http://dx.doi.org/10.3390/biom11091366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467212PMC
September 2021

Awareness of Rheumatic Heart Disease in Egypt: A National Multicenter Study.

J Cardiovasc Dev Dis 2021 Sep 4;8(9). Epub 2021 Sep 4.

Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Background: While the prevalence of rheumatic heart disease (RHD) in Egypt is relatively high, data on the awareness of Egyptians about the cause of RHD are lacking.

Methods: Using a pre-tested questionnaire, we performed a multicenter survey of outpatients attending 15 university hospitals across Egypt.

Results: A total of 6958 participants were interviewed. Most subjects (81.7%) reported a previous experience of sore throat. Seeking treatment, most patients (69.3%) consulted a medical professional, while the others relied on self/peer medication. Individuals consulting a physician received antibiotics more frequently than those who did not (89.1 vs. 38.7%; OR: 12.4, 95% CI 10.8-14.1). The median RHD knowledge score in our sample was 4 (IQR = 6). While most subjects (56.3%) claimed knowledge of the complications of an untreated sore throat, only a third (34%) were aware of the association between sore throat and RHD. In a multivariate analysis, older age (Mean Difference [MD]: 1.58, 95% CI 1.37-1.79), female gender (MD: 0.89, 95% CI 0.75-1.04), higher education (MD: 1.10, 95% CI 0.90-1.30), and being interviewed outside Cairo (MD: 0.67, 95% CI 0.51-0.82) were significant predictors of knowledge about RHD.

Conclusion: The current study showed low levels of awareness on the cause of RHD among Egyptians and highlights a pressing need for interventions to address this public knowledge gap.
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http://dx.doi.org/10.3390/jcdd8090108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466231PMC
September 2021

Monitoring of Antimicrobial Susceptibility of Bacteria Isolated from Poultry Farms from 2014 to 2018.

Vet Med Int 2021 10;2021:6739220. Epub 2021 Sep 10.

Reference Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, Agricultural Research Center (ARC), Nadi El-Seid Street, Dokki P.O. Box 246, Giza 12618, Egypt.

The current situation of antibiotic resistance of most bacterial pathogens was a threat to the poultry and public health with increasing economic losses. Regarding this problem, monitoring of the circulating microorganisms occurred with the antibiotic resistance profile. A total of 657 different samples from internal organs (liver, heart, lung, and yolk) and paper-lining chick boxes were collected from native chicken farms which were submitted to the Reference Laboratory for Veterinary Quality Control on Poultry Production in the period from 2014 to 2018 for the detection of , (. , and . The bacterial isolates were tested for their antimicrobial susceptibility by disk diffusion technique. was isolated from 128 out of 657 (19.5%), . was isolated from 496 out of 657 (75.5%), and species was isolated from 497 out of 657 (75.6%). All positive samples were examined for antibiotic resistance against 10 different antibiotics, and the highest percentage all over the five years was against penicillin, ampicillin, and tetracycline. All E. positive samples were examined for antibiotic resistance against 14 different antibiotics, and the highest percentage all over the five years was with ampicillin, tetracycline, norfloxacin, streptomycin, and danofloxacin. All positive sample species were examined for antibiotic resistance against 14 different antibiotics, and the highest percentage of resistance all over the five years was shown with tetracycline, streptomycin, ampicillin, and nalidixic acid.
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http://dx.doi.org/10.1155/2021/6739220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448596PMC
September 2021

miRNome profiling in Duchenne muscular dystrophy; identification of asymptomatic and manifesting female carriers.

Biosci Rep 2021 Sep;41(9)

Biotechnology Department, Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology, Borg Al Arab 21934, Egypt.

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder that occurs due to inactivating mutations in DMD gene, leading to muscular dystrophy. Prediction of pathological complications of DMD and the identification of female carriers are important research points that aim to reduce disease burden. Herein, we describe a case of a late DMD patient and his immediate female family members, who all carry same DMD mutation and exhibited varied degrees of symptoms. In our study, we sequenced the whole miRNome in leukocytes and plasma of the family members and results were validated using real-time PCR. Our results highlighted the role of miR-409-3p, miR-424-5p, miR-144-3p as microRNAs that show correlation with the extent of severity of muscular weakness and can be used for detection of asymptomatic carriers. Cellular and circulating levels of miR-494-3p had shown significant increase in symptomatic carriers, which may indicate significant roles played by this miRNA in the onset of muscular weakness. Interestingly, circulating levels of miR-206 and miR-410-3p were significantly increased only in the severely symptomatic carrier. In conclusion, our study highlighted several miRNA species, which could be used in predicting the onset of muscle and/or neurological complications in DMD carriers.
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http://dx.doi.org/10.1042/BSR20211325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450315PMC
September 2021

Synthesis, spectroscopic and computational studies on hydrogen bonded charge transfer complex of duvelisib with chloranilic acid: Application to development of novel 96-microwell spectrophotometric assay.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Aug 21;264:120287. Epub 2021 Aug 21.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt. Electronic address:

Duvelisib (DUV) is a is a small-molecule with inhibitory action for phosphoinositide 3-kinase (PI3K). It has been recently approved for the effective treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Novel charge transfer complex (CTC) between DUV, as electron donor, with chloranilic acid (CLA), as π electron acceptor has been synthesized and characterized using different spectroscopic and thermogravimetric techniques. UV-visible spectroscopy ascertained the formation of the CTC in different solvents of varying polarity indexes and dielectric constants via formation of new broad absorption band with maximum absorption peak (λ) in the range of 488-532 nm. The molar absorptivity of the CTC was dependent on the polarity index and dielectric constant of the solvent; the correlation coefficients were 0.9955 and 0.9749, respectively. The stoichiometric ratio of DUV:CLA was 1:1. Electronic spectral analysis was conducted for characterization of the complex in terms of its electronic constants. Computational calculation for atomic charges of energy minimized DUV was conducted and the site of interaction on DUV molecule was assigned. The solid-state CTC of DUV:CLA (1:1) was synthesized, and its structure was characterized by UV-visible, mass, FT-IR, and H NMR spectroscopic techniques. Both FT-IR and H NMR confirmed that both CT and hydrogen bonding contributed to the molecular composition of the complex. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric assay (MW-SPA) for DUV. The assay limits of detection and quantitation were 0.57 and 1.72 µg/well, respectively. The assay was validated and all validation parameters were acceptable. The method was implemented successfully with great precision and accuracy to the analysis of the DUV in its bulk and capsules.
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http://dx.doi.org/10.1016/j.saa.2021.120287DOI Listing
August 2021

Regulation of Keap-1/Nrf2/AKT and iNOS/NF-κB/TLR4 signals by apocynin abrogated methotrexate-induced testicular toxicity: Mechanistic insights and computational pharmacological analysis.

Life Sci 2021 Nov 25;284:119911. Epub 2021 Aug 25.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt.

Aim: Male reproductive toxicity is becoming of growing significance due to clinical chemotherapy usage. Methotrexate (MTX) is an anti-folate used on a large scale for different tumors and autoimmune conditions. Despite its wide clinical use, MTX is associated with severe testicular intoxication. The exact underlying mechanism is unclear.

Methods: Our study was conducted to explore the pathogenesis mechanism of MTX-induced testicular damage and the potential testicular protective effects of apocynin (APO) on testicular injury induced by single i.p. MTX (20 mg/kg). APO was administered orally (100 mg/kg) for ten days.

Results: As compared to rats given MTX alone, co-administration of MTX with APO demonstrated multiple beneficial effects evidenced by a marked increase in testosterone, FSH, and LH and significantly restored testes histopathological alterations. Mechanistically, APO restored antioxidant status through up-regulation of Nrf2, cytoglobin, PPAR-γ, SIRT1, AKT, and p-AKT, while effectively lowering Keap-1. Moreover, APO significantly attenuated inflammation by down-regulating NF-κB-p65, iNOS, and TLR4 expressions confirmed by in-silico evidence. Additionally, network pharmacology analysis, a bioinformatics approach, was used to decipher various cellular processes' molecular mechanisms.

Significance: The current investigation proves the beneficial effects of APO in MTX-associated testicular damage through activation of cytoglobin, Keap-1/Nrf2/AKT, PPAR-γ, SIRT1, and suppressing of TLR4/NF-κB-p65 signal. Our data collectively encourage extending the investigation to the clinical setting to explore APO effects in MTX-treated patients.
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http://dx.doi.org/10.1016/j.lfs.2021.119911DOI Listing
November 2021

Flavonoid-Coated Gold Nanoparticles as Efficient Antibiotics against Gram-Negative Bacteria-Evidence from In Silico-Supported In Vitro Studies.

Antibiotics (Basel) 2021 Aug 12;10(8). Epub 2021 Aug 12.

Department of Microbiology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo 11837, Egypt.

Flavonoids are a class of bioactive plant-derived natural products that exhibit a broad range of biological activities, including antibacterial ones. Their inhibitory activity toward Gram-positive bacterial was found to be superior to that against Gram-negative ones. In the present study, a number of flavonoid-coated gold nanoparticles (GNPs) were designed to enhance the antibacterial effects of chrysin, kaempferol, and quercetin against a number of Gram-negative bacteria. The prepared GNPs were able to conjugate to these three flavonoids with conjugation efficiency ranging from 41% to 80%. Additionally, they were able to exert an enhanced antibacterial activity in comparison with the free flavonoids and the unconjugated GNPs. Quercetin-coated GNPs were the most active nano-conjugates and were able to penetrate the cell wall of . A number of in silico experiments were carried out to explain the conjugation efficiency and the antibacterial mechanisms of these flavonoids as follows: (i) these flavonoids can efficiently bind to the glutathione linker on the surface of GNPs via H-bonding; (ii) these flavonoids, particularly quercetin, were able to increase the bacterial membrane rigidity, and hence decrease its functionality; (iii) these flavonoids can inhibit 's DNA gyrase (Gyr-B) with IC values ranging from 0.9 to 3.9 µM. In conclusion, these bioactive flavonoid-based GNPs are considered to be very promising antibiotic candidates for further development and evaluation.
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http://dx.doi.org/10.3390/antibiotics10080968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389009PMC
August 2021

Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2.

Mar Drugs 2021 Jul 22;19(8). Epub 2021 Jul 22.

School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2's spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein's RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (), sulfated polymannuroguluronate (SPMG) (), sulfated mannan (), sulfated heterorhamnan (), and chondroitin sulfate E (CS-E) (). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.
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http://dx.doi.org/10.3390/md19080406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401819PMC
July 2021

Single nucleotide polymorphisms, gene expression and serum profile of immune and antioxidant markers associated with postpartum disorders susceptibility in Barki sheep.

Anim Biotechnol 2021 Aug 18:1-13. Epub 2021 Aug 18.

Department of Animal Health and Poultry, Animal and Poultry Production Division, Desert Research Center (DRC), Cairo, Egypt.

The objective of this study was to explore the immunological and antioxidant alterations associated with ovine postpartum disorders. Blood samples were collected from 90 adult Barki ewes and allocated into three equal-sized groups (30 ewes each): control group (CG), inflammatory postpartum disorders group (IPG) and non-inflammatory postpartum disorders group (NIPG). PCR-DNA sequencing approach was carried out for (256-bp) and (456-bp) genes, and nucleotide sequence variations were noticed to be associated with postpartum disorders resistance/susceptibility. Gene expression profile was also evaluated and levels of , , , , and were significantly up-regulated in ewes affected with postpartum disorders than resistant ones, while and genes pattern elicited an opposite trend. Exploring serum profile also showed a significant increase of IL-1α, IL-1β, IL-6, TNF-α, MDA and NO in IPG compared to their correspond values in NIPG and CG. However, serum levels of IL-10, CAT, GSH and GPx were significantly decreased. This study highlights that SNPs in and genes could be genetic markers for postpartum disorders resistance/susceptibility in Barki ewes. Gene expression alongside serum profiles of antioxidant markers could also be used to follow-up the immune status of ewes to build up an effective management protocol.
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http://dx.doi.org/10.1080/10495398.2021.1964984DOI Listing
August 2021

Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR-4/NF-κB, and JAK1/STAT3 signaling in cyclophosphamide-intoxicated rats.

J Biochem Mol Toxicol 2021 Aug 13:e22889. Epub 2021 Aug 13.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.

Hemorrhagic cystitis is a potentially deadly complication associated with radiation therapy and chemotherapy. This study explored the protective effect of edaravone (ED) on cyclophosphamide (CP)-induced hemorrhagic cystitis, oxidative stress, and inflammation in rats. The animals received 20 mg/kg ED for 10 days and a single injection of 200 mg/kg CP on day 7. CP induced tissue injury manifested by the diffuse necrotic changes, disorganization of lining mucosa, focal hemorrhagic patches, mucosal/submucosal inflammatory cells infiltrates, and edema. CP increased malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha, and interleukin 6 (IL-6), decreased IL-10, and upregulated toll-like receptor 4 (TLR-4), nuclear factor-kappa B (NF-κB) p65, Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) in the urinary bladder of rats. ED effectively prevented the histopathological alterations, decreased MDA, NO, and inflammatory mediators, and downregulated TLR-4, NF-κB, JAK1, and STAT3 in CP-induced rats. Treatment with ED upregulated ikβ kinase β, IL-10, nuclear factor-erythroid 2 related factor 2 (Nrf2), and cytoglobin, and boosted glutathione, superoxide dismutase, and glutathione S-transferase. Molecular docking simulations revealed the ability of ED to bind TLR-4, NF-κB, JAK1, and STAT3. In vitro, ED increased the cytotoxic activity of CP against HeLa, Caco-2, and K562 cell lines. In conclusion, ED prevented CP-induced hemorrhagic cystitis in rats by attenuating oxidative stress, suppressing TLR-4/NF-κB, and JAK1/STAT3 signaling and boosted Nrf2, cytoglobin, and antioxidants.
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http://dx.doi.org/10.1002/jbt.22889DOI Listing
August 2021

Restricted Use of Echocardiography in Suspected Endocarditis during COVID-19 Lockdown: A Multidisciplinary Team Approach.

Cardiol Res Pract 2021 30;2021:5565200. Epub 2021 Jul 30.

National Heart and Lung Institute, Imperial College London, London, UK.

Background: Infective endocarditis (IE) is challenging to manage in the COVID-19 lockdown period, in part given its reliance on echocardiography for diagnosis and management and the associated virus transmission risks to patients and healthcare workers. This study assesses utilisation of the endocarditis team (ET) in limiting routine echocardiography, especially transoesophageal echocardiography (TOE), in patients with suspected IE, and explores the effect on clinical outcomes.

Methods: All patients discussed at the ET meeting at Imperial College Healthcare NHS Trust during the first lockdown in the UK (23 March to 8 July 2020) were prospectively included and analysed in this observational study.

Results: In total, 38 patients were referred for ET review (71% male, median age 54 [interquartile range 48, 65.5] years). At the time of ET discussion, 21% had no echo imaging, 16% had point-of-care ultrasound only, and 63% had formal TTE. In total, only 16% underwent TOE. The ability of echocardiography, in those where it was performed, to affect IE diagnosis according to the Modified Duke Criteria was significant (=0.0099); however, sensitivity was not affected. All-cause mortality was 17% at 30 days and 25% at 12 months from ET discussion in those with confirmed IE.

Conclusion: Limiting echocardiography in patients with a low pretest probability (not probable or definite IE according to the Modified Duke Criteria) did not affect the diagnostic ability of the Modified Duke Criteria to rule out IE in this small study. Moreover, restricting nonessential echocardiography, and importantly TOE, in patients with suspected IE through use of the ET did not impact all-cause mortality.
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http://dx.doi.org/10.1155/2021/5565200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342166PMC
July 2021

Eco-Friendly UPLC-MS/MS Method for Determination of a Fostamatinib Metabolite, Tamatinib, in Plasma: Pharmacokinetic Application in Rats.

Molecules 2021 Jul 31;26(15). Epub 2021 Jul 31.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh P.O. Box 11451, Saudi Arabia.

Fostamatinib is a prodrug of the active metabolite tamatinib, which is a spleen tyrosine kinase (Syk) inhibitor used in the treatment of primary chronic adult immune thrombocytopenia and rheumatoid arthritis. A highly sensitive, rapid, reliable, and green method was developed and validated using ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) for quantification of tamatinib in rat plasma. Ibrutinib was used as internal standard and liquid-liquid extraction was applied using tert-butyl methyl ether. The analyte was separated on an Acquity CSH C (2.1 mm × 100 mm, 1.7 µm) column using mobile phase consisting of 10 mM ammonium acetate and acetonitrile (10:90) and the flow rate was 0.25 mL/min. Electrospray ionization (ESI) was carried out in positive mode. Quantitation of tamatinib and the IS was performed using multiple reaction monitoring mode with precursor-to-product transitions of / 471.1 > 122.0 and / 441.1 > 84.0, respectively. The calibration range was 0.1-1000.0 ng/mL and the linearity of the method was ≥0.997. The developed method greenness was investigated. All principal parameters for the method, including linearity, accuracy, precision, recovery, and stability, were within acceptable ranges. Tamatinib pharmacokinetic study in rats was successfully carried out using the developed method.
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http://dx.doi.org/10.3390/molecules26154663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348403PMC
July 2021

Anti-Alzheimer chemical constituents of Morus macroura Miq.: chemical profiling, in silico and in vitro investigations.

Food Funct 2021 Sep 20;12(17):8078-8089. Epub 2021 Jul 20.

Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Herein, we investigated both fruits and leaves of Morus macroura Miq. as a potential source of bioactive compounds against Alzheimer's disease (AD). LC-HRMS-assisted chemical profiling of its extracts showed that they are a rich source of diverse phytochemicals. Among the 29 identified compounds in both the fruit and leaf extracts, moracin D, chrysin, resveratrol, and ferulic acid were predicted to pass the human blood-brain barrier (BBB), and hence, reach their therapeutic targets in the brain. Subsequently, these compounds were subjected to a comprehensive pharmacophore-based screening for their protein targets relevant to AD using two independent software programs (i.e. Swiss Target Prediction and PharmMapper). The results of this initial virtual screening were further refined by a number of docking and molecular dynamic simulation experiments to suggest a number of crucial AD-related proteins (e.g. acetylcholine esterase, β-secretase, and monoamine oxidase) as potential targets for these compounds. Finally, in vitro testing was performed to validate the in silico investigation's results, where chrysin, resveratrol, and ferulic acid were found to inhibit the predicted AD-related enzymes with IC values comparable with those of the reference inhibitors. Additionally, they were able to inhibit the aggregation of amyloid-beta, one of the hallmarks in AD pathogenesis, and to exhibit considerable antioxidant capacity. Our results highlighted Morus macroura compounds as future anti-Alzheimer chemical leads.
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http://dx.doi.org/10.1039/d1fo01177dDOI Listing
September 2021

Potential therapeutic effects of avenanthramide-C against lung toxicity caused by silver nanoparticles injection in rats.

Pak J Pharm Sci 2021 Jan;34(1(Supplementary)):337-343

Pharmaceutical Sciences Department, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia/Department of Biochemistry, Faculty of Pharmacy, Al Azhar University, Cairo, Egypt.

Most clinical investigations about the impact of nanoparticles on cells and tissues show that nanoparticles may enter the human body by means of respiratory tracts. Humans, animals, plants and environments are continually presented to a wide scope of business items containing silver nanoparticles (Ag NPs) in their piece. Ag NPs, utilized in various consumer products as room showers, surface cleaners, wound dressings, food storage containers and many textiles. The current examination planned to explore the defensive role of Avenanthramide-C (Avns) contrary to the lung toxicity initiated by Ag NPs injection in rats. 40 male Wistar rats were separated into 4 groups (Gp1, control; Gp2, Avns; Gp3, Ag NPs; Gp4, Ag NPs+Avns). Current results revealed that; Ag NPs induced a significant depletion in RBCs count, hemoglobin, platelets counts and a significant increase in total WBCs, lung injury, cyclooxygenase-2 (COX2) and TNFα expressions as compared to control. Treatments of Ag NPs with Avenanthramide-C extract (Ag NPs+Avns) improved the lung structure and blood complete pictures as compared to Ag NPs group.
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January 2021

Hepatoprotective effects of phytochemicals berberine and umbelliferone against methotrexate-induced hepatic intoxication: experimental studies and in silico evidence.

Environ Sci Pollut Res Int 2021 Jul 13. Epub 2021 Jul 13.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt.

Chemotherapeutic drugs are used effectively to manage wide types of malignancies, but their therapeutic use is limited due to their associated hepatic intoxication. The current study sheds light on the effect of phytochemicals berberine (BBR) and umbelliferone (UMB) on methotrexate (MTX)-induced hepatic intoxication. Forty-eight rats were allocated to normal, BBR (50 mg/kg orally for 10 days), UMB (30 mg/kg orally for 10 days), MTX (20 mg/kg at the 5th day), BBR+MTX, and UMB+MTX. With regard to MTX, the results of this investigation reveal potent amelioration of MTX hepatotoxicity by BBR and UMB through reduction of the elevated serum levels of ALT, ALP, AST, and LDH confirmed by the attenuation of histopathological abrasion in liver tissues. BBR and UMB markedly restored antioxidant status. More importantly, BBR resulted in reducing P mitogen-activated protein kinase (PMAPK), nuclear factor kappa-B (NF-κB), and Kelch-like ECH-associated protein 1 (Keap-1) genes and enhanced mRNA expression of Nrf-2 (P < 0.05). Interestingly, in silico studies via molecular docking pinpointed the binding modes of BBR and UMB to the binding pocket residues of PMAPK, NF-κB, and Keap-1 and demonstrated a promising inhibition of Keap-1, PMAPK, and NF-κB. BBR and UMB reduced the expression of pro-apoptotic protein Bax and apoptotic protein caspase-3 as well as increased the expression of anti-apoptotic protein Bcl-2. Therefore, BBR and UMB may denote promising therapeutic agents that can avert hepatic intoxication in patients receiving MTX.
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http://dx.doi.org/10.1007/s11356-021-15358-4DOI Listing
July 2021

Scaffold Hopping of α-Rubromycin Enables Direct Access to FDA-Approved Cromoglicic Acid as a SARS-CoV-2 M Inhibitor.

Pharmaceuticals (Basel) 2021 Jun 5;14(6). Epub 2021 Jun 5.

School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.

The COVID-19 pandemic is still active around the globe despite the newly introduced vaccines. Hence, finding effective medications or repurposing available ones could offer great help during this serious situation. During our anti-COVID-19 investigation of microbial natural products (MNPs), we came across α-rubromycin, an antibiotic derived from ATCC19743, which was able to suppress the catalytic activity (IC = 5.4 µM and = 3.22 µM) of one of the viral key enzymes (i.e., M). However, it showed high cytotoxicity toward normal human fibroblasts (CC = 16.7 µM). To reduce the cytotoxicity of this microbial metabolite, we utilized a number of in silico tools (ensemble docking, molecular dynamics simulation, binding free energy calculation) to propose a novel scaffold having the main pharmacophoric features to inhibit M with better drug-like properties and reduced/minimal toxicity. Nevertheless, reaching this novel scaffold synthetically is a time-consuming process, particularly at this critical time. Instead, this scaffold was used as a template to explore similar molecules among the FDA-approved medications that share its main pharmacophoric features with the aid of pharmacophore-based virtual screening software. As a result, cromoglicic acid ( cromolyn) was found to be the best hit, which, upon in vitro M testing, was 4.5 times more potent (IC = 1.1 µM and = 0.68 µM) than α-rubromycin, with minimal cytotoxicity toward normal human fibroblasts (CC > 100 µM). This report highlights the potential of MNPs in providing unprecedented scaffolds with a wide range of therapeutic efficacy. It also revealed the importance of cheminformatics tools in speeding up the drug discovery process, which is extremely important in such a critical situation.
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http://dx.doi.org/10.3390/ph14060541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229550PMC
June 2021

A Highly Sensitive Nonextraction-Assisted HPLC Method with Fluorescence Detection for Quantification of Duvelisib in Plasma Samples and its Application to Pharmacokinetic Study in Rats.

Drug Des Devel Ther 2021 21;15:2667-2677. Epub 2021 Jun 21.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.

Background: Duvelisib (DUV) is a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor. It has been recently granted an accelerated approval for treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It is also effective in therapy of T-cell lymphoma, solid tumors, and non-Hodgkin's lymphoma. In literature, there is no method valid for quantitation of DUV in human plasma for its therapeutic monitoring and pharmacokinetic studies.

Purpose: The purpose of this study is the establishment of a highly sensitive HPLC method with fluorescence detection for quantitation of DUV in plasma for its therapeutic monitoring and pharmacokinetic studies of DUV.

Methods: The resolution of DUV and the internal standard (IS) olaparib (OLA) was achieved on Nucleosil CN column, with a mobile phase composed of acetonitrile:water (25:75, v/v) at a flow rate of 1.7 mL min. The fluorescence of both DUV and OLA was detected at 410 nm after excitation at 280 nm. The method was validated according to the guidelines of bioanalytical method validation.

Results: The method was linear in the range of 5-100 ng mL, and its limit of detection (LOD) and limit of quantitation (LOQ) were 2.12 ng mL and 7 ng mL, respectively. The precisions of the method were ≤ 8.26%, and its accuracies were ≥ 95.32%. All the other validation parameters were satisfactory. The proposed method was successfully employed to the investigation of the pharmacokinetic profile of DUV in rats following a 25 mg/kg single dose of oral administration.

Conclusion: The method is characterized with high sensitivity, accuracy, simple sample pretreatment, rapidity, eco-friendly as it consumes low volumes of organic solvent in the mobile phase and has high analysis throughput as its run time was short (~ 10 min).
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http://dx.doi.org/10.2147/DDDT.S318714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232391PMC
June 2021

Voice Rehabilitation by Voice Prostheses After Total Laryngectomy: A Systematic Review and Network Meta-Analysis for 11,918 Patients.

J Speech Lang Hear Res 2021 07 29;64(7):2668-2681. Epub 2021 Jun 29.

School of Tropical Medicine and Global Health, Nagasaki University, Japan.

Purpose Our aim was to assess the different voice prostheses (VPs) to identify the most efficient, safest, patient-tailored, longest lifetime, and inexpensive VPs and assess the different factors affecting their quality. Method In September 2017, 15 databases were searched to include all randomized controlled trials. A new search was done in May 2019 to include all other study design articles, which include all the new-era VPs subtypes. Network meta-analysis (NMA) was applied to all 27 outcomes, besides NMA overall and partial order setting was done by using Hasse scatter plots. values were used in NMA, where the best VPs are approaching one and the least approaches zero. Meta-analysis was done for the rest of the outcomes. Results Two hundred one articles were eligible for inclusion in our study ( = 11,918). Provox-2 was significantly the most efficient and safest device concerning the most patient preference (odds ratio [] = 33.88 [0.65, 1762.24]; = .92), the least dislodgement (risk ratio [RR] = 0.27 [0.13, 0.57]; = .79), the least airflow resistance (RR = 0.42 [0.08, 2.11]; = .84), the least granulation formation (RR = 0.73 [0.02, 26.32]; = .60), and the least VPs' inaccurate size (RR = 0.77 (0.23, 2.61); = .66). Heat and moisture exchanger addition showed a significant increase in maximum phonation time and breathing experience, with values (1 and .59), respectively. While heat and moisture exchanger addition showed a significant decline in stoma cleaning frequency, coughing frequency, forced expectoration, sputum production, sleeping problems, and loosening of adhesive, with values (.99, .72, .69, .96, 1, and 0.96), respectively, Groningen low resistance and Nijdam were considered the worst devices with both overall mean value of .44. Conclusions Provox-2 is considered the best choice as being the most preferable for patients, with the least airflow resistance, dislodgment, granulation formation, and prosthesis inaccurate size. Groningen low resistance and Nijdam were considered the worst devices according to our analysis. Supplemental Material https://doi.org/10.23641/asha.14802903.
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http://dx.doi.org/10.1044/2021_JSLHR-20-00597DOI Listing
July 2021

Protective prospects of eco-friendly synthesized selenium nanoparticles using Moringa oleifera or Moringa oleifera leaf extract against melamine induced nephrotoxicity in male rats.

Ecotoxicol Environ Saf 2021 Sep 23;221:112424. Epub 2021 Jun 23.

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, El-Sharkia Province 44511, Egypt.

Nanotechnology is used in a wide range of applications, including medical therapies that precisely target disease prevention and treatment. The current study aimed firstly, to synthesize selenium nanoparticles (SeNPs) in an eco-friendly manner using Moringa oleifera leaf extract (MOLE). Secondly, to compare the protective effects of green-synthesized MOLE-SeNPs conjugate and MOLE ethanolic extract as remedies for melamine (MEL) induced nephrotoxicity in male rats. One hundred and five male Sprague Dawley rats were divided into seven groups (n = 15), including 1 control, 2 MOLE (800 mg/kg BW), 3 SeNPs (0.5 mg/kg BW), 4 MOLE-SeNPs (200 μg/kg BW), 5 MEL (700 mg/kg BW), 6 MEL+MOLE, and 7 MEL+MOLE SeNPs. All groups were orally gavaged day after day for 28 days. SeNPs and the colloidal SeNPs were characterized by TEM, SEM, and DLS particle size. SeNPs showed an absorption peak at a wavelength of 530 nm, spherical shape, and an average size between 3.2 and 20 nm. Colloidal SeNPs absorption spectra were recorded between 400 and 700 nm with an average size of 3.3-17 nm. MEL-induced nephropathic alterations represented by a significant increase in serum creatinine, urea, blood urea nitrogen (BUN), renal TNFα, oxidative stress-related indices, and altered the relative mRNA expression of apoptosis-related genes Bax, Caspase-3, Bcl2, Fas, and FasL. MEL-induced array of nephrotoxic morphological changes, and up-regulated immune-expression of proliferating cell nuclear antigen (PCNA) and proliferation-associated nuclear antigen Ki-67. Administration of MOLE or MOLE-SeNPs significantly reversed MEL-induced renal function impairments, oxidative stress, histological alterations, modulation in the relative mRNA expression of apoptosis-related genes, and the immune-expression of renal PCNA and Ki-67. Conclusively, the green-synthesized MOLE-SeNPs and MOLE display nephron-protective properties against MEL-induced murine nephropathy. This study is the first to report these effects which were more pronounced in the MOLE group than the green biosynthesized MOLE-SeNPs conjugate group.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112424DOI Listing
September 2021

Xanthine oxidase inhibitory activity of Euphorbia peplus L. phenolics.

Comb Chem High Throughput Screen 2021 Jun 8. Epub 2021 Jun 8.

Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, Saudi Arabia.

Background: Various phenolics show inhibitory activity towards xanthine oxidase (XO), an enzyme that generates reactive oxygen species which cause oxidative damage.

Objective: This study investigated the XO inhibitory activity of Euphorbia peplus phenolics.

Methods: The dried powdered aerial parts of E. peplus were extracted, fractioned and phenolics were isolated and identified. The XO inhibitory activity of E. peplus extract (EPE) and the isolated phenolics was investigated in vitro and in vivo.

Results: Three phenolics were isolated from the ethyl acetate fraction of E. peplus. All isolated compounds and the EPE showed inhibitory activity towards XO in vitro. In hyperuricemic rats, EPE and the isolated phenolics decreased uric acid and XO activity. Molecular docking showed the binding modes of isolated phenolics with XO, depicting significant interactions with the active site amino acid residues. Molecular dynamics simulation trajectories confirmed the interaction of isolated phenolics with XO by forming hydrogen bonds with the active site residues. Also, the root mean square (RMS) deviations of XO and phenolics-XO complexes achieved equilibrium and fluctuated during the 10 ns MD simulations. The radius of gyration and solvent accessible surface area investigations showed that different systems were stabilized at ≈ 2500 ps. The RMS fluctuations profile depicted that the drug binding site exhibited a rigidity behavior during the simulation.

Conclusion: In vitro, in vivo and computational investigations showed the XO inhibitory activity of E. peplus phenolics. These phenolics might represent promising candidates for the development of XO inhibitors.
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http://dx.doi.org/10.2174/1386207324666210609104456DOI Listing
June 2021

Targeting allosteric sites of human aromatase: a comprehensive and workflow to find potential plant-based anti-breast cancer therapeutics.

J Enzyme Inhib Med Chem 2021 Dec;36(1):1334-1345

School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley, UK.

Recent findings suggested several allosteric pockets on human aromatase that could be utilised for the development of new modulators able to inhibit this enzyme in a new mechanism. Herein, we applied an integrated -based approach supported by enzyme-based and cell-based validation assays to select the best leads able to target these allosteric binding sites from a small library of plant-derived natural products. Chrysin, apigenin, and resveratrol were found to be the best inhibitors targeting the enzyme's substrate access channel and were able to produce a competitive inhibition with IC values ranged from 1.7 to 15.8 µM. Moreover, they showed a more potent antiproliferative effect against ER+ (MCF-7) than ER- one (MDA-MB-231) cell lines. On the other hand, both pomiferin and berberine were the best hits for the enzyme's haem-proximal cavity producing a non-competitive inhibition (IC 15.1 and 21.4 µM, respectively) and showed selective antiproliferative activity towards MCF-7 cell lines.
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http://dx.doi.org/10.1080/14756366.2021.1937145DOI Listing
December 2021

Cytotoxic Potential, Metabolic Profiling, and Liposomes of sp. Crude Extract Supported by in silico Analysis.

Int J Nanomedicine 2021 4;16:3861-3874. Epub 2021 Jun 4.

Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.

Introduction: Sponge- sp. (Family: Spongiidae) is a coastal sponge that possesses a broad variety of natural-products. However, the exact chemical constituents and cytotoxic activity of the extract are still undefinable.

Methodology: In the present study, the metabolomic profiling of sp. dereplicated 20 compounds, utilizing liquid chromatography coupled with high-resolution mass spectrometry (LC-HRESIMS). derived crude extract, before and after encapsulation within nanosized liposomes, was in vitro screened against hepatic, breast, and colorectal carcinoma human cell lines (HepG2, MCF-7, and Caco-2, respectively).

Results: The identified metabolites were fit to diverse chemical classes, covering diterpenes, an indole alkaloid, sesterterpenoid, sterol, and methylherbipoline salt. Comprehensive in silico experiments predicted several compounds in the sponge-derived extract (eg, compounds -) to have an anticancer potential via targeting multiple targets. The crude extract showed moderate antiproliferative activities towards studied cell lines with IC values range from 10.7 to 12.4 µg/mL. The formulated extract-containing liposomes (size 141±12.3nm, PDI 0.222, zeta potential 20.8 ± 2.3), significantly enhanced the in vitro anticancer activity of the entrapped extract (IC values ranged from 1.7 to 4.1 µg/mL).

Discussion: Encapsulation of both the hydrophilic and the lipophilic components of the extract within the lipid-based nanovesicles enhanced the cellular uptake and accessibility of the entrapped cargo. This study introduces liposomal nano-vesicles as a promising approach to improve the therapeutic potential of sponge-derived extracts.
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http://dx.doi.org/10.2147/IJN.S310720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187037PMC
June 2021
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