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Article ; Online: DNA-induced fusion between lipid domains of peptide-lipid hybrid vesicles.

Rahman, Md Mofizur / Abosheasha, Mohammed A / Ito, Yoshihiro / Ueda, Motoki

Chemical communications (Cambridge, England)

2022 Volume 58, Issue 84, Page(s) 11799–11802

Abstract: Peptide-lipid hybrid vesicles were prepared with complementary DNA strands in their lipid domains. Hybridization of the complementary DNA strands induced the controlled fusion of the vesicles during repeated heating and cooling cycles. Vesicle fusion was ...

Abstract	Peptide-lipid hybrid vesicles were prepared with complementary DNA strands in their lipid domains. Hybridization of the complementary DNA strands induced the controlled fusion of the vesicles during repeated heating and cooling cycles. Vesicle fusion was indicated by a decrease in the efficiency of Förster resonance energy transfer between lipid-localized probes (from 72 to 42%) and transmission electron microscopy analysis. We suggest that this approach is a general strategy for the creation of polymersomes with membrane-fusion functionality.
MeSH term(s)	DNA, Complementary ; Membrane Fusion ; DNA ; Peptides ; Lipids ; Lipid Bilayers
Chemical Substances	DNA, Complementary ; DNA (9007-49-2) ; Peptides ; Lipids ; Lipid Bilayers
Language	English
Publishing date	2022-10-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d2cc03997d
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Article ; Online: Tubular Assembly Formation Induced by Leucine Alignment along the Hydrophobic Helix of Amphiphilic Polypeptides.

Abosheasha, Mohammed A / Itagaki, Toru / Ito, Yoshihiro / Ueda, Motoki

International journal of molecular sciences

2021 Volume 22, Issue 21

Abstract: The introduction of α-helical structure with a specific helix-helix interaction into an amphipathic molecule enables the determination of the molecular packing in the assembly and the morphological control of peptide assemblies. We previously reported ... ...

Abstract	The introduction of α-helical structure with a specific helix-helix interaction into an amphipathic molecule enables the determination of the molecular packing in the assembly and the morphological control of peptide assemblies. We previously reported that the amphiphilic polypeptide SL12 with a polysarcosine (PSar) hydrophilic chain and hydrophobic α-helix (l-Leu-Aib)
MeSH term(s)	Hydrophobic and Hydrophilic Interactions ; Leucine/chemistry ; Models, Molecular ; Nanotubes/chemistry ; Peptides/chemistry ; Protein Conformation ; Sarcosine/analogs & derivatives ; Sarcosine/chemistry
Chemical Substances	Peptides ; polysarcosine (25951-24-0) ; Leucine (GMW67QNF9C) ; Sarcosine (Z711V88R5F)
Language	English
Publishing date	2021-11-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222112075
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Article ; Online: Differential mechanisms of autophagy in cancer stem cells: Emphasizing gastrointestinal cancers.

El-Gowily, Afnan H / Abosheasha, Mohammed A

Cell biochemistry and function

2020 Volume 39, Issue 2, Page(s) 162–173

Abstract: Gastrointestinal (GI) cancers are one of the most common forms of malignancies and still are the most important cause of cancer-related mortality worldwide. Autophagy is a conserved catabolic pathway involving lysosomal degradation and recycling of whole ...

Abstract	Gastrointestinal (GI) cancers are one of the most common forms of malignancies and still are the most important cause of cancer-related mortality worldwide. Autophagy is a conserved catabolic pathway involving lysosomal degradation and recycling of whole cellular components, which is essential for cellular homeostasis. For instance, it acts as a pivotal intracellular quality control and repair mechanism but also implicated in cell reformation during cell differentiation and development. Indeed, GI cancer stem cells (CSCs) are thought to be responsible for tumour initiation, traditional therapies resistance, metastasis and tumour recurrence. Molecular mechanisms of autophagy in normal vs CSCs gain great interest worldwide. Here, we shed light on the role of autophagy in normal stem cells differentiation for embryonic progression and its role in maintaining the activity and self-renewal capacity of CSCs which offer novel viewpoints on promising cancer therapeutic strategies based on the differential roles of autophagy in CSCs.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Autophagy ; Biomarkers, Tumor/metabolism ; Cell Differentiation ; Embryonic Development ; Gastrointestinal Neoplasms/metabolism ; Gastrointestinal Neoplasms/pathology ; Humans ; Neoplastic Stem Cells/cytology ; Neoplastic Stem Cells/metabolism ; Signal Transduction ; Tumor Microenvironment
Chemical Substances	Biomarkers, Tumor ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2020-05-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	283643-9
ISSN	1099-0844 ; 0263-6484
ISSN (online)	1099-0844
ISSN	0263-6484
DOI	10.1002/cbf.3552
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Article ; Online: Superiority of cilostazol among antiplatelet FDA-approved drugs against COVID 19 M

Abosheasha, Mohammed A / El-Gowily, Afnan H

Drug development research

2020 Volume 82, Issue 2, Page(s) 217–229

Abstract: Coronavirus disease 2019 (COVID 19) was first identified in Wuhan, China near the end of 2019. To date, COVID-19 had spread to almost 235 countries and territories due to its highly infectious nature. Moreover, there is no vaccine or Food and Drug ... ...

Abstract	Coronavirus disease 2019 (COVID 19) was first identified in Wuhan, China near the end of 2019. To date, COVID-19 had spread to almost 235 countries and territories due to its highly infectious nature. Moreover, there is no vaccine or Food and Drug Administration (FDA)-approved drug. More time is needed to establish one of them. Consequently, the drug repurposing approach seems to be the most attractive and quick solution to accommodate this crisis. In this regard, we performed molecular docking-based virtual screening of antiplatelet FDA-approved drugs on the key two viral target proteins: main protease (M
MeSH term(s)	COVID-19/drug therapy ; Cilostazol/metabolism ; Cilostazol/therapeutic use ; Coronavirus 3C Proteases/metabolism ; Drug Approval ; Drug Evaluation, Preclinical ; Drug Repositioning ; Eicosapentaenoic Acid/analogs & derivatives ; Eicosapentaenoic Acid/metabolism ; Eicosapentaenoic Acid/therapeutic use ; Epoprostenol/metabolism ; Epoprostenol/therapeutic use ; Humans ; Iloprost/metabolism ; Iloprost/therapeutic use ; Molecular Docking Simulation ; Platelet Aggregation Inhibitors/metabolism ; Platelet Aggregation Inhibitors/therapeutic use ; Prasugrel Hydrochloride/metabolism ; Prasugrel Hydrochloride/therapeutic use ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; United States ; United States Food and Drug Administration
Chemical Substances	Platelet Aggregation Inhibitors ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; eicosapentaenoic acid ethyl ester (6GC8A4PAYH) ; Eicosapentaenoic Acid (AAN7QOV9EA) ; Epoprostenol (DCR9Z582X0) ; Coronavirus 3C Proteases (EC 3.4.22.28) ; Prasugrel Hydrochloride (G89JQ59I13) ; Iloprost (JED5K35YGL) ; Cilostazol (N7Z035406B)
Keywords	covid19
Language	English
Publishing date	2020-09-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	604587-x
ISSN	1098-2299 ; 0272-4391
ISSN (online)	1098-2299
ISSN	0272-4391
DOI	10.1002/ddr.21743
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Article ; Online: Potential antiviral properties of antiplatelet agents against SARS-CoV-2 infection: an in silico perspective.

Abosheasha, Mohammed A / El-Gowily, Afnan H / Elfiky, Abdo A

Journal of thrombosis and thrombolysis

2021 Volume 53, Issue 2, Page(s) 273–281

Abstract: SARS-CoV-2 represents the causative agent of the current pandemic (COVID-19). The drug repurposing technique is used to search for possible drugs that can bind to SARS-CoV-2 proteins and inhibit viral replication. In this study, the FDA-approved ... ...

Abstract	SARS-CoV-2 represents the causative agent of the current pandemic (COVID-19). The drug repurposing technique is used to search for possible drugs that can bind to SARS-CoV-2 proteins and inhibit viral replication. In this study, the FDA-approved antiplatelets are tested against the main protease and spike proteins of SARS-CoV-2 using in silico methods. Molecular docking and molecular dynamics simulation are used in the current study. The results suggest the effectiveness of vorapaxar, ticagrelor, cilostazol, cangrelor, and prasugrel in binding the main protease (M
MeSH term(s)	Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Cilostazol ; Coronavirus 3C Proteases/antagonists & inhibitors ; Humans ; Lactones ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Platelet Aggregation Inhibitors/pharmacology ; Pyridines ; SARS-CoV-2/drug effects ; Spike Glycoprotein, Coronavirus/antagonists & inhibitors ; Ticagrelor
Chemical Substances	Antiviral Agents ; Lactones ; Platelet Aggregation Inhibitors ; Pyridines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28) ; Ticagrelor (GLH0314RVC) ; Cilostazol (N7Z035406B) ; vorapaxar (ZCE93644N2)
Language	English
Publishing date	2021-09-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-021-02558-5
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Zs.A 4352: Show issues

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Article ; Online: Hypoxia-responsive pullulan-based nanoparticles as erlotinib carriers.

Bera, Hriday / Abosheasha, Mohammed A / Ito, Yoshihiro / Ueda, Motoki

International journal of biological macromolecules

2021 Volume 191, Page(s) 764–774

Abstract: A hypoxia-responsive pullulan-based co-polymer was developed to assess its efficacy to deliver erlotinib (ERL) to the cervical cancer cells. Upon exposure to hypoxic condition, the synthesized and structurally characterized co-polymer i.e. succinyl ... ...

Abstract	A hypoxia-responsive pullulan-based co-polymer was developed to assess its efficacy to deliver erlotinib (ERL) to the cervical cancer cells. Upon exposure to hypoxic condition, the synthesized and structurally characterized co-polymer i.e. succinyl pullulan-g-6-(2-nitroimidazole) hexylamine (Pull-SA-HA-NI) exhibited a hypochromic shift in the UV spectra and alteration in its self-assembled structures as compared to the control co-polymer, succinyl pullulan-g-hexylamine (Pull-SA-HA). Its corresponding ERL-loaded nanoparticles (NPs) displayed an attenuated crystallinity of pure ERL with excellent drug-trapping capacity (DEE, 94.23 ± 1.36%) and acceptable zeta potential (+39.21 ± 1.09 mV) and diameter (84.10 ± 2.10 nm) values. These also evidenced a faster drug release profile under hypoxic condition relative to the normoxic condition. The cellular internalization of the NPs was mediated through the energy-dependent endocytic process, which could utilize its multiple pathways (i.e., macropinocytosis, clathrin- and caveolae-mediated endocytosis). The ERL-loaded NPs suppressed HeLa cell proliferation and induced apoptosis more efficiently than the pristine drug.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Drug Liberation ; Erlotinib Hydrochloride/administration & dosage ; Glucans/chemistry ; HeLa Cells ; Humans ; Nanoparticles/chemistry ; Tumor Hypoxia
Chemical Substances	Antineoplastic Agents ; Glucans ; pullulan (8ZQ0AYU1TT) ; Erlotinib Hydrochloride (DA87705X9K)
Language	English
Publishing date	2021-09-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2021.09.122
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Article ; Online: Etherified pullulan-polyethylenimine based nanoscaffolds improved chemosensitivity of erlotinib on hypoxic cancer cells.

Bera, Hriday / Abosheasha, Mohammed A / Ito, Yoshihiro / Ueda, Motoki

Carbohydrate polymers

2021 Volume 271, Page(s) 118441

Abstract: The current research endeavor aimed to accomplish hypoxia-responsive polyethyleneimine-conjugated carboxymethyl pullulan-based co-polymer (CMP-HA-NI-PEI-NBA) bearing nitroaromatic subunits to efficiently deliver erlotinib (ERL) to reverse its hypoxia- ... ...

Abstract	The current research endeavor aimed to accomplish hypoxia-responsive polyethyleneimine-conjugated carboxymethyl pullulan-based co-polymer (CMP-HA-NI-PEI-NBA) bearing nitroaromatic subunits to efficiently deliver erlotinib (ERL) to reverse its hypoxia-induced resistance in cancer cells. As compared to a control co-polymer (CMP-HA-MI-PEI-BA) devoid of hypoxia-sensitive moieties, this scaffold demonstrated a hypochromic shift in the UV spectra and rapid dismantling of its self-assembled architecture upon exposure to simulated hypoxic condition. The hypoxia-responsive co-polymer encapsulated ERL with desirable loading capacity (DEE, 63.05 ± 2.59%), causing attenuated drug crystallinity. The drug release rate of the scaffold under reducing condition was faster relative to that of non-reducing environment. Their cellular uptake occurred through an energy-dependent endocytic process, which could exploit its caveolae/lipid raft-mediated internalization pathway. The ERL-loaded scaffolds more efficiently induced apoptosis and suppressed the proliferation of drug-resistant hypoxic HeLa cells than the pristine ERL. Hence, this study presented a promising drug delivery nanoplatform to overcome hypoxia-evoked ERL resistance.
MeSH term(s)	Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Hypoxia/physiology ; Cell Proliferation/drug effects ; Drug Carriers/chemical synthesis ; Drug Carriers/chemistry ; Drug Liberation ; Erlotinib Hydrochloride/chemistry ; Erlotinib Hydrochloride/pharmacology ; Glucans/chemical synthesis ; Glucans/chemistry ; HeLa Cells ; Humans ; Nanostructures/chemistry ; Polyethyleneimine/chemical synthesis ; Polyethyleneimine/chemistry
Chemical Substances	Antineoplastic Agents ; Drug Carriers ; Glucans ; carboxymethylpullulan ; Polyethyleneimine (9002-98-6) ; Erlotinib Hydrochloride (DA87705X9K)
Language	English
Publishing date	2021-07-16
Publishing country	England
Document type	Journal Article
ZDB-ID	1501516-6
ISSN	1879-1344 ; 0144-8617
ISSN (online)	1879-1344
ISSN	0144-8617
DOI	10.1016/j.carbpol.2021.118441
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Article ; Online: Tubular Assembly Formation Induced by Leucine Alignment along the Hydrophobic Helix of Amphiphilic Polypeptides

Mohammed A. Abosheasha / Toru Itagaki / Yoshihiro Ito / Motoki Ueda

International Journal of Molecular Sciences, Vol 22, Iss 12075, p

2021 Volume 12075

Abstract: The introduction of α-helical structure with a specific helix–helix interaction into an amphipathic molecule enables the determination of the molecular packing in the assembly and the morphological control of peptide assemblies. We previously reported ... ...

Abstract	The introduction of α-helical structure with a specific helix–helix interaction into an amphipathic molecule enables the determination of the molecular packing in the assembly and the morphological control of peptide assemblies. We previously reported that the amphiphilic polypeptide SL12 with a polysarcosine (PSar) hydrophilic chain and hydrophobic α-helix ( l -Leu-Aib) 6 involving the LxxxLxxxL sequence, which induces homo-dimerization due to the concave–convex interaction, formed a nanotube with a uniform 80 nm diameter. In this study, we investigated the importance of the LxxxLxxxL sequence for tube formation by comparing amphiphilic polypeptide SL4A4L4 with hydrophobic α-helix ( l -Leu-Aib) 2 -( l -Ala-Aib) 2 -( l -Leu-Aib) 2 and SL12. SL4A4L4 formed spherical vesicles and micelles. The effect of the LxxxLxxxL sequence elongation on tube formation was demonstrated by studying assemblies of PSar- b -( l -Ala-Aib)-( l -Leu-Aib) 6 -( l -Ala-Aib) (SA2L12A2) and PSar-b-( l -Leu-Aib) 8 (SL16). SA2L12A2 formed nanotubes with a uniform 123 nm diameter, while SL16 assembled into vesicles. These results showed that LxxxLxxxL is a necessary and sufficient sequence for the self-assembly of nanotubes. Furthermore, we fabricated a double-layer nanotube by combining two kinds of nanotubes with 80 and 120 nm diameters—SL12 and SA2L12A2. When SA2L12A2 self-assembled in SL12 nanotube dispersion, SA2L12A2 initially formed a rolled sheet, the sheet then wrapped the SL12 nanotube, and a double-layer nanotube was obtained.
Keywords	helix–helix interaction ; helix orientation ; secondary structure ; peptide assembly ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Superiority of cilostazol among antiplatelet FDA ‐approved drugs against COVID 19 M pro and spike protein

Abosheasha, Mohammed A. / El‐Gowily, Afnan H.

Drug Development Research ; ISSN 0272-4391 1098-2299

Drug repurposing approach

2020

Keywords	Drug Discovery ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
DOI	10.1002/ddr.21743
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Article: Association between a novel G94A single nucleotide polymorphism in

Abosheasha, Mohammed A / Zahran, Faten / Bessa, Sahar S / El-Magd, Mohammed A / Mohamed, Tarek M

Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences

2019 Volume 24, Page(s) 62

Abstract: Background: Na: Materials and methods: A total number of 150 individuals were subclassified into healthy controls (: Results: The biochemical results exhibited a significant reduction in fasting C-Peptide and activity of Na: Conclusion: Thus, ... ...

Abstract	Background: Na Materials and methods: A total number of 150 individuals were subclassified into healthy controls ( Results: The biochemical results exhibited a significant reduction in fasting C-Peptide and activity of Na Conclusion: Thus, allele A of G94A SNP (rs1060366) could be a risk allele for diabetes susceptibility among Egyptian patients.
Language	English
Publishing date	2019-07-24
Publishing country	India
Document type	Journal Article
ZDB-ID	2513029-8
ISSN	1735-7136 ; 1735-1995
ISSN (online)	1735-7136
ISSN	1735-1995
DOI	10.4103/jrms.JRMS_975_18
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