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"Sheikh, Ibrahim"
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An engineered thermally tolerant apo-cytochrome scaffold for metal-less incorporation of heme derivative
2023
Cytochrome c 552 from Thermus thermophilus is one of the hot topics for creating smart biomaterials as it possesses remarkable stability, is tolerant to multiple mutations and has therefore been recently reported for a number of functionalizations upon substitution of the original prosthetic group with an artificial prosthetic group. However, all of the substitutions were driven by the coordination through the axial ligands followed by complete reconstitution with a metal–porphyrin complex. This limits the scope of the cytochrome c for incorporating a metal-less non-natural heme species that could improve the versatility of cytochrome c for a new generation of engineered cytochrome proteins for further enhancement in their functionalities such as biocatalysts. In this connection, a new variant of Cytochrome c ( rC 552 C14A) from Thermus thermophilus was reported, where an easy approach to remove the original prosthetic group was achieved, followed by the incorporation of a number of metal-PPIX derivatives that ultimately led to the formation of artificial c-type cytochromes through covalent bonding. The apo-cytochrome was found to be thermally tolerant and to possess a distinctive overall structure as that of the wild type, as was evident from the corresponding CD spectra, which ultimately encouraged reconstitution with a metal-less protoporphyrin derivative for better understanding the role of axial ligands in the reconstitution process. Successful reconstitution was achieved, resulting in a new type of Cytochrome b -type artificial protein without the metal in its active site, indicating the non-involvement of the axial ligand. In order to prove the non-involvement of the axial ligand, a subsequent double mutant (C14A/M69A) was constructed, replacing the methionine at 69 position with non-coordinating alanine residue. Accordingly, the apo-C14A/M69A was prepared and found to be extremely stable as the earlier mutants and the WT showed no signs of denaturation, even at the elevated temperature of 98°C. Subsequently, heme b was successfully incorporated into the apo-C14A/M69A, which demonstrated itself as a highly thermally tolerant protein scaffold for incorporating a metal-less artificial prosthetic group in the absence of the axial ligand. Further improvement in the reconstitution process is achieved by replacing the methionine at 69 position with phenyl alanine (C14A/M69F mutant), resulting in further stabilization of heme species, possibly through non-covalent π–interactions, as corroborated by molecular docking.
Journal Article
Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety
by
Al-Humaidi, Jehan Y.
,
Gomha, Sobhi M.
,
Alamri, Abdulwahab
in
1,3,4-thiadiazoles
,
1,3-thiazoles
,
anticancer activity
2022
Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea (2) was prepared and reacted with various hydrazonoyl halides 3a–h, α-haloketones 5a–d, 3-chloropentane-2,4-dione 7a and ethyl 2-chloro-3-oxobutanoate 7b, which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles 4a–h, 3-phenyl-4-arylthiazoles 6a–d and the 4-methyl-3- phenyl-5-substituted thiazoles 8a,b, respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole 4h was found to be most promising and an excellent performer against both cancer cell lines (IC50 = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC50 = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK.
Journal Article
Removal Properties of Anionic Dye Eosin by Cetyltrimethylammonium Organo-Clays: The Effect of Counter-Ions and Regeneration Studies
by
Liu, Yan
,
Kooli, Fethi
,
Oudghiri Hassani, Hicham
in
anionic dye
,
Cations
,
Cetrimonium Compounds - chemistry
2018
The organo-clays (OCs) were prepared by a cation exchange reaction between surfactant (cetyltrimethylammonium, C16TMA) from different counterions (Bromide, Chloride, and Hydroxide). The effect of the counterions was investigated on the physico-chemical properties of the prepared organo-clays. The highest uptake of organic cations (1.60 mmol/g) was achieved using cetyl trimethylammonium bromide solution and the lowest value (0.93 mmol/g) was obtained after modification with cetyl trimethylammonium hydroxide solution starting from the same initial ratio of mmol/g of clay greater than 2.40. The arrangement of C16TMA cations within the interlayer space was assumed to be perpendicular with a tilt angle of 32° to the plane of clay sheets instead of being parallel to the clay surface using C16TMAOH solution at the same ratio. Different techniques were used to characterize these materials. The thermal stability of these organ-clays was investigated using an in-situ X-ray diffraction (XRD) technique. The decomposition of the surfactant moiety occurred at temperatures higher than 215 °C and was accompanied with a shrinkage of the basal spacing value to 1.42 nm. These materials were applied in the removal of an acid dye “eosin.” The removed amount of eosin depended on the initial concentrations and the content of surfactants in the organo-clays. The removal of eosin was found to be an endothermic process. The maximum amount of 90 mg/g was achieved. The preheated treatment temperature of two selected OCs did affect the removal properties of eosin. A progressive reduction was observed at temperatures higher than 200 °C. The regeneration of spent OCs was studied and acceptable removal efficiency was maintained after 4 to 6 cycles depending on the used initial concentrations.
Journal Article
Eosin Removal by Cetyl Trimethylammonium-Cloisites: Influence of the Surfactant Solution Type and Regeneration Properties
2019
The effect of the counteranion of hexadecyltrimethylammonium salts on the physico-chemical properties of organoclays was investigated, using a selected natural clay mineral with a cation exchange capacity of 95 meq/100 g. The uptake amount of C16 cations was dependent on the hexadecyltrimethylammonium (C16) salt solution used, the organoclay prepared from C16Br salt solution exhibited a value of 1. 05 mmole/g higher than those prepared from C16Cl and C16OH salt solutions. The basal spacing of these organoclays was in the range of 1.81 nm to 2.10 nm, indicating a similar orientation of the intercalated surfactants, and could indicated that the excess amount of surfactants, above the cation exchange capacity of 0.95 meq/g could be adsorbed on the external surface of the clay mineral sheets. These organoclays were found to be stable in neutral, acidic, and basic media. The thermal stability of these organoclays was carried out using thermogravimetric analysis and in-situ X-ray diffraction (XRD) techniques. The decomposition of the surfactant occurred at a maximum temperature of 240 °C, accompanied with a decrease of the basal spacing value close to 1.42 nm. The application of these organoclays was investigated to remove an acidic dye, eosin. The removal amount was related to the initial used concentrations, the amount of the surfactants contents, and to the preheated temperatures of the organoclays. The removal was found to be endothermic process with a maximum amount of 55 mg of eosin/g of organoclay. The value decreased to 25 mg/g, when the intercalated surfactants were decomposed. The reuse of these organoclays was limited to four regeneration recycles with a reduction of 20 to 30%. However, noticeable reduction between 35% to 50% of the initial efficiency, was achieved after the fifth cycle, depending of the used organoclays.
Journal Article
Five Techniques of Osseodensification in One Case
by
Sheikh Ibrahim, Abdulkarim
,
Abdo, Anas
,
Hassan Jaafo, Mohamad
in
Bone density
,
Densah Burs
,
Dental implants
2024
Initial stability of implants is an important factor for the osseointegration of dental implants. Initial stability of implants can be lost when the bone is insufficient in cases of immediate implantation or when the bone density is insufficient, making it difficult to ensure good initial stability. Many techniques have been used to increase bone density. This study tested the use of five methods to increase bone density in one patient. This study concluded that the five methods used were effective in densifying the bone and achieving clinically acceptable primary stability in low-density bone.
Journal Article
Case Report: A new modification of Loma Linda pouch technique
by
Alkhouri, Issam
,
Sheikh Ibrahim, Abdulkarim
,
Redwan, Hazem
in
Bone Grafting; Collagen Membrane; Perforation; Pouch Technique; Sinus Lifting
,
Bone grafts
,
Bone Transplantation
2025
Dental implants provide a reliable treatment option for completely or partially edentulous patients. In case of a membrane perforation, the gap can be closed using a piece of resorbable collagen membrane or by suturing the Schneiderian membrane using a resorbable suture. The present study shows a new development in this technique, which involves modifying the design of the absorbable membrane and using pins to fix the membrane. This study concluded that the novel design of the collagen membrane and its fixation with the pins led to greater stability of the bone graft and led to subsequent bone gain that enables dental implantation. Still, this technique requires a histological study to determine the nature of the bone formed.
Journal Article
Application of Organo-Magadiites for the Removal of Eosin Dye from Aqueous Solutions: Thermal Treatment and Regeneration
2018
Na-magadiite exchanged with cetyl-trimethylammonium cations provided organophilic silicate materials that allowed for the effective removal of the acidic dye “eosin”. The organic cations were intercalated into the interlayer spacing of the layered silicate via an exchange reaction between the organic cations from their bromide salt and the solid Na-magadiite at room temperature. Different techniques were used to characterize the effect of the initial concentration of the surfactant on the structure of the organo-magadiites. The C, H, and N analysis indicated that a maximum of organic cations of 0.97 mmol/g was achieved and was accompanied by an expansion of the basal spacing of 3.08 nm, with a tilted angle of 59° to the silicate layers. The conformation of the organic surfactants was probed using solid-state 13C, finding mainly the trans conformation similar to that of the starting cetyl trimethylammonium bromide salt (C16TMABr). Thermal gravimetric analysis was carried out to study the thermal stability of the resulting organo-magadiites. The intercalated surfactants started to decompose at 200 °C, with a mass loss percentage of 8% to 25%, depending on the initial loading of the surfactant, and was accompanied by a decrease of the basal spacing from 3.16 nm to 2.51 nm, as deduced from the in situ X-ray diffraction studies. At temperatures below 220 °C, an expansion of the basal spacing from 3.15 to 3.34 nm occurred. These materials were used as a removal agent for the anionic dye eosin. The maximum amount of the dye removed was related to the organic cation content and to the initial concentration of eosin, with an improvement from 2.5 mg/g to 80.65 mg/g. This value decreased when the organo-magadiite was preheated at temperatures above 200 °C. The regeneration tests indicated that an 85% removal efficiency was maintained after six cycles of use for the organo-magadiite using Ci of 200 mg/L.
Journal Article
Radical Mediated Rapid In Vitro Formation of c-Type Cytochrome
2022
A cytochrome c552 mutant from Thermus thermophilus HB8 (rC552 C14A) was reported, where the polypeptide with replaced Cys14 by alanine, overexpressed in the cytosol of E. coli. The apo-form of the C14A mutant (apo-C14A) without the original prosthetic group was obtained by simple chemical treatments that retained compact conformation amenable to reconstitution with heme b and zinc(II)-protoporphyrin(IX), gradually followed by spontaneous formation of a covalent bond between the polypeptide and porphyrin ring in the reconstituted apo-C14A. Further analysis suggested that the residual Cys11 and vinyl group of the porphyrin ring linked through the thiol-ene reaction promoted by light under ambient conditions. In this study, we describe the kinetic improvement of the covalent bond formation in accordance with the mechanism of the photoinduced thiol-ene reaction, which involves a thiyl radical as a reaction intermediate. Adding a radical generator to the reconstituted C14A mutant with either heme-b or zinc(II) porphyrin accelerated the bond-forming reaction, which supported the involvement of a radical species in the reaction. Partial observation of the reconstituted C14A in a dimer form and detection of sulfuryl radical by EPR spectroscopy indicated a thiyl radical on Cys11, a unique cysteinyl residue in rC552 C14A. The covalent bond forming mediated by the radical generator was also adaptable to the reconstituted apo-C14A with manganese(II)-protoporphyrin(IX), which also exhibits light-mediated covalent linkage formation. Therefore, the radical generator extends the versatility of producing c-type-like cytochrome starting from a metallo-protoporphyrin(IX) and the apo-C14A instantaneously.
Journal Article
Case Report: A new modification of Loma Linda pouch technique version 2; peer review: 1 approved with reservations
by
Alkhouri, Issam
,
Sheikh Ibrahim, Abdulkarim
,
Redwan, Hazem
in
Bone Grafting; Collagen Membrane; Perforation; Pouch Technique; Sinus Lifting
2025
Dental implants provide a reliable treatment option for completely or partially edentulous patients. In case of a membrane perforation, the gap can be closed using a piece of resorbable collagen membrane or by suturing the Schneiderian membrane using a resorbable suture. The present study shows a new development in this technique, which involves modifying the design of the absorbable membrane and using pins to fix the membrane. This study concluded that the novel design of the collagen membrane and its fixation with the pins led to greater stability of the bone graft and led to subsequent bone gain that enables dental implantation. Still, this technique requires a histological study to determine the nature of the bone formed.
Journal Article
A smart secure virtual reality immersive application for alzheimer’s and dementia patients
2025
Alzheimer’s disease (AD) poses significant challenges for the elderly, leading to cognitive decline, social isolation, and lower quality of life. Current interventions often require cumbersome wearable devices e.g. the camera-based monitoring that may raise privacy concerns. However, these issues are not fully addressed previously. To fill this gap, this research proposes a new framework in non-invasive combination of Virtual Reality (VR), Voice recognition, and Artificial Intelligence (AI) to act as a supportive system for people with AD. The system provides a brand-new approach that tailored cognitive stimulation and companionship through the immersive VR scenarios, memory games, virtual trips, and an AI assistant together as a single platform. The AI-based assessment of the patient is employed to ensure that the experience is more relevant and helpful to the patient. The voice recognition is the most simple and easy user-interface. The security measures include access controls, encryption and continuous monitoring of cloud patient data. The initial study has been promising evidenced by the outcome of involving patients with Alzheimer’s and dementia, their families, and clinicians. Participants reported heightened interest, better quality of life, less sense of isolation, and improved cognitive functioning, which have particularly achieved one of our goals, in patients’ well-beings in mental healthcare. The research indicates a significant step forward enhancing the quality of support for both cognitive function and social interaction for older adults with AD and dementia. In comparison with other currently existing systems, our newly developed integrated framework has made additional contributions to the areas of AD in dynamic cognitive adaptation, bilingual interaction, and secure real-time personalized system.
Journal Article