Publications by authors named "H P S Abdul Khalil"

731 Publications

Engineered s-Triazine-based dendrimer-honokiol conjugates as targeted MMP-2/9 inhibitors for halting hepatocellular carcinoma.

ChemMedChem 2021 Sep 21. Epub 2021 Sep 21.

Alexandria University, Department of Physics and Chemistry, Faculty of Education, Alexandria University, Egypt., Alexandria, EGYPT.

Despite the advances in developing MMP-2/9 inhibitors, off-target side effects and pharmacokinetics problems remain major challenges hindering their clinical success in cancer therapy. However, recent targeting strategies obviously revitalized MMP research. Herein, we introduce new s-triazine-based dendrimers endowed with intrinsic MMP-2/9 inhibitory potential and tetherable to hepatocellular carcinoma-specific targeting ligands and anticancer agents via biodegradable linkages for targeted therapy. The designed dendrimeric platform was built with potential zinc-binding branching linkers (hydrazides) and termini (carboxylic acids and hydrazides) to confer potency against MMP-2/9. Preliminary cytotoxicity screening and MMP-2/9 inhibition assay of the free dendrimers revealed promising potency (MMP-9; IC50=0.35-0.57µM, MMP-2; IC50=0.39-0.77µM) within their safe doses (EC100=94.15-42.75µM). The hydrazide dendrimer was comparable to NNGH and superior to the carboxylic acid analogue. MTT assay showed that the free dendrimers were superior to the reference anticancer agent honokiol. Their anticancer potency was enhanced by HK conjugation, targeting ligands installation and PEGylation as exemplified by the hydrazide dendrimer conjugate (TPG3-NH2)-SuHK-FA-SuPEG (Huh-7; IC50=5.54µM, HepG-2; IC50=10.07µM) being 4 folds more active than HK, followed by the carboxylic acid conjugate (TPG3-OH)-HK-LA-PEG (Huh-7; IC50=14.97, HepG-2; IC50=21.29µM). This was consistent with apoptosis studies.
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http://dx.doi.org/10.1002/cmdc.202100465DOI Listing
September 2021

Fabrication and application of composite adsorbents made by one-pot electrochemical exfoliation of graphite in surfactant ionic liquid/nanocellulose mixtures.

Phys Chem Chem Phys 2021 Sep 15;23(35):19313-19328. Epub 2021 Sep 15.

School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.

Previously, surfactant-assisted exfoliated graphene oxide (sEGO) formed with the triple-chain surfactant TC14 (sodium 1,4-bis(neopentyloxy)-3-(neopentylcarbonyl)-1,4-dioxobutane-2-sulfonate) was applied in wastewater treatment. The extent of dye-removal and the adsorption capacity of the sEGO formed with this triple-chain surfactant outperformed those of two other systems, namely, the di-chain version of TC14 (AOT14; sodium 1,2-bis-(2,2-dimethyl-propoxycarbonyl)-ethanesulfonate) and the single-chain surfactant sodium -dodecylsulfate. In the present study, to further optimise the surfactant chemical structure, the sodium ion of TC14 was substituted with 1-butyl-3-methyl-imidazolium (BMIM) generating surfactant ionic liquids (SAILs; 1-butyl-3-imidazolium 1,4-bis(neopentyloxy)-3-(neopentyloxycarbonyl)-1,4-dioxobutane-2-sulfonate), hereafter denoted as BMIM-TC14. This SAIL, together with nanofibrillated kenaf cellulose (NFC), was used to electrochemically exfoliate graphite, yielding BMIM-TC14 sEGO/NFC composites. These highly hydrophobic polymer composites were then used for the removal of methylene blue (MB) from aqueous solution. H NMR spectroscopy was used to elucidate the structure of the synthesised SAILs. The morphologies of the resulting nanocomposites were investigated using Raman spectroscopy, field-emission scanning electron microscopy, and high-resolution transmission electron microscopy. Analysis using small-angle neutron scattering was performed to examine the aggregation behaviour of sEGO and custom-made SAILs. Zeta potential, surface tension, and dynamic light-scattering measurements were used to study the aqueous properties and colloidal stability of the suspension. Amongst the surfactants tested, BMIM-TC14 sEGO/NFC exhibited the highest MB adsorption ability, achieving 99% dye removal under optimum conditions. These results highlight the importance of modifying the hydrophilic moieties of amphiphilic compounds to improve the performance of sEGO/NFC composites as effective adsorbents for wastewater treatment.
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http://dx.doi.org/10.1039/d1cp02206gDOI Listing
September 2021

A Case of Clinically Diagnosed ANCA Negative Granulomatosis With Polyangiitis.

Ear Nose Throat J 2021 Sep 14:1455613211037086. Epub 2021 Sep 14.

Department of Otorhinolaryngology-Head and Neck Surgery, University Hospitals Plymouth NHS Trust, Plymouth, Devon, United Kingdom.

Significance Statement: Granulomatosis with polyangitis (GPA) is a systemic necrotizing vasculitis comprising of inflammation of small and medium-sized vessels. It typically presents with involvement of the upper and lower airways as well as the kidneys. If left untreated, end-organ damage may occur. Hematological investigations typically demonstrate the presence of antinuclear cytoplasmic antibodies (ANCA). Here, we discuss an unusual presentation of ANCA negative GPA, presenting initially with nasal symptoms.
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http://dx.doi.org/10.1177/01455613211037086DOI Listing
September 2021

Effective Targeting of Raf-1 and Its Associated Autophagy by Novel Extracted Peptide for Treating Breast Cancer Cells.

Front Oncol 2021 27;11:682596. Epub 2021 Aug 27.

Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt.

Breast cancer is one of the most common causes of death in women worldwide and has harmful influence on their psychological state during therapy. Multikinase inhibitors have become effective drugs for treating a variety of cancer diseases such as breast cancer. A purified short peptide (H-P) was isolated from the natural honey and tested for its potential regulatory role in breast cancer cells compared with the effectiveness of the anticancer drug, Sorafenib (SOR), using MCF-7, EFM-19, and MCF-10A cell lines. Furthermore, we investigated the direct connection between Raf-1 activation and cellular autophagy as potential targets of SOR and H-P extract using RNA interference. Interestingly, the treatment with H-P showed competitive regulation of phosphorylated Raf-1, MEK1/2, and matched autophagy-related LC3B without any detectable toxic effects in the non-tumorigenic epithelial cells. Unlike SOR, the regulation of Raf-1 protein and autophagic machinery by the novel H-P extract showed neglected levels of the released proinflammatory cytokine. This regulation of cytokine secretion by H-P resulted in decreasing the expression level of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in treated cells. Moreover, the transfection of MCF-7 cells with small interference RNA (siRNA) antagonist Raf-1 expression markedly reduced the expression of LC3B, while it increased the expression of NF-kB1 and NF-kB2, indicating the potential cross-link between Raf-1, autophagy, and NF-kB effector. Collectively, these findings suggest that H-P-mediated Raf-1, MEK1/2, LC3B, and NF-kB provide a novel and efficacious multikinase inhibitor for treating breast cancer without detectable cytotoxic effects.
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http://dx.doi.org/10.3389/fonc.2021.682596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430328PMC
August 2021

Functional Adhesion of Pectin Biopolymers to the Lung Visceral Pleura.

Polymers (Basel) 2021 Sep 2;13(17). Epub 2021 Sep 2.

Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Pleural injuries and the associated "air leak" are the most common complications after pulmonary surgery. Air leaks are the primary reason for prolonged chest tube use and increased hospital length of stay. Pectin, a plant-derived heteropolysaccharide, has been shown to be an air-tight sealant of pulmonary air leaks. Here, we investigate the morphologic and mechanical properties of pectin adhesion to the visceral pleural surface of the lung. After the application of high-methoxyl citrus pectin films to the murine lung, we used scanning electron microscopy to demonstrate intimate binding to the lung surface. To quantitatively assess pectin adhesion to the pleural surface, we used a custom adhesion test with force, distance, and time recordings. These assays demonstrated that pectin-glycocalyceal tensile adhesive strength was greater than nanocellulose fiber films or pressure-sensitive adhesives ( < 0.001). Simultaneous videomicroscopy recordings demonstrated that pectin-glycocalyceal adhesion was also stronger than the submesothelial connective tissue as avulsed surface remnants were visualized on the separated pectin films. Finally, pleural abrasion and hyaluronidase enzyme digestion confirmed that pectin binding was dependent on the pleural glycocalyx ( < 0.001). The results indicate that high methoxyl citrus pectin is a promising sealant for the treatment of pleural lung injuries.
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http://dx.doi.org/10.3390/polym13172976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433721PMC
September 2021
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