| 1. |
- Belal, Amany, et al.
(författare)
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Therapeutic Potential of Zeolites/Vitamin B12 Nanocomposite on Complete Freunds Adjuvant-Induced Arthritis as a Bone Disorder: In Vivo Study and Bio-Molecular Investigations
- 2023
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a long-term autoimmune disease. As nanotechnology has advanced, a growing number of nanodrugs have been used in the treatment of RA due to their unique physical and chemical properties. The purpose of this study was to assess the therapeutic potential of a novel zeolite/vitamin B12 nanocomposite (Nano ZT/Vit B12) formulation in complete Freunds adjuvant (CFA)-induced arthritis. The newly synthesized Nano ZT/Vit B12 was fully characterized using various techniques such as XRD, FT-IR, BET analysis, HERTEM, SEM, practical size, zeta potential, XRF, and EDX. The anti-arthritic, anti-inflammatory, and antioxidant activities as well as the immunomodulation effect of Nano ZT/Vit B12 on the CFA rat model of arthritis were examined. Histopathologic ankle joint injuries caused by CFA intrapedal injection included synovium hyperplasia, inflammatory cell infiltration, and extensive cartilage deterioration. The arthritic rats Nano ZT/Vit B12 supplementation significantly improved these effects. Furthermore, in arthritic rats, Nano ZT/Vit B12 significantly reduced serum levels of RF and CRP, as well as the levels of IL-1 beta, TNF-alpha, IL-17, and ADAMTS-5, while increasing IL-4 and TIMP-3 levels. Nano-ZT/Vit B12 significantly declined the LPO level and increased antioxidant activities, such as GSH content and GST activity, in the arthritic rats. In arthritic rats, Nano ZT/Vit B12 also reduced TGF-beta mRNA gene expression and MMP-13 protein levels. Collectively, Nano ZT/Vit B12 seems to have anti-arthritic, anti-inflammatory, and antioxidant properties, making it a promising option for RA in the future.
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| 2. |
- Belal, Amany, et al.
(författare)
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A Novel Hydroxyapatite/Vitamin B-12 Nanoformula for Treatment of Bone Damage: Preparation, Characterization, and Anti-Arthritic, Anti-Inflammatory, and Antioxidant Activities in Chemically Induced Arthritic Rats
- 2023
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The usage of nanomaterials for rheumatoid arthritis (RA) treatment can improve bioavailability and enable selective targeting. The current study prepares and evaluates the in vivo biological effects of a novel hydroxyapatite/vitamin B-12 nanoformula in Complete Freunds adjuvant-induced arthritis in rats. The synthesized nanoformula was characterized using XRD, FTIR, BET analysis, HERTEM, SEM, particle size, and zeta potential. We synthesized pure HAP NPs with 71.01% loading weight percentages of Vit B12 and 49 mg/g loading capacity. Loading of vitamin B-12 on hydroxyapatite was modeled by Monte Carlo simulation. Anti-arthritic, anti-inflammatory, and antioxidant effects of the prepared nanoformula were assessed. Treated arthritic rats showed lower levels of RF and CRP, IL-1 beta, TNF-alpha, IL-17, and ADAMTS-5, but higher IL-4 and TIMP-3 levels. In addition, the prepared nanoformula increased GSH content and GST antioxidant activity while decreasing LPO levels. Furthermore, it reduced the expression of TGF-beta mRNA. Histopathological examinations revealed an improvement in joint injuries through the reduction of inflammatory cell infiltration, cartilage deterioration, and bone damage caused by Complete Freunds adjuvant. These findings indicate that the anti-arthritic, antioxidant, and anti-inflammatory properties of the prepared nanoformula could be useful for the development of new anti-arthritic treatments.
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| 3. |
- El-Sayed, Ashraf S. A., et al.
(författare)
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Aspergillus nidulans thermostable arginine deiminase-Dextran conjugates with enhanced molecular stability, proteolytic resistance, pharmacokinetic properties and anticancer activity
- 2019
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Ingår i: Enzyme and microbial technology. - : Elsevier. - 0141-0229 .- 1879-0909. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- The potential anticancer activity of arginine deiminase (ADI) via deimination of L-arginine into citrulline has been extensively verified against various arginine-auxotrophic tumors, however, the higher antigenicity, structural instability and in vivo proteolysis are the major challenges that limit this enzyme from further clinical implementation. Since, this clinically applied enzyme was derived from Mycobacterium spp, thus, searching for ADI from eukaryotic microbes "especially thermophilic fungi" could have a novel biochemical conformational and catalytic properties. Aspergillus nidulans ADI was purified with 5.3 folds, with molecular subunit structure 48 kDa and entire molecular mass 120 kDa, ensuring its homotrimeric identity. The peptide fingerprinting analysis revealing the domain Glu(95)-Gly(96)-Gly(97) as the conserved active site of A. nidulans ADI, with higher proximity to Mycobacterium ADI Glade IV. In an endeavor to fortify the structural stability and anticancer activity of A. nidulans ADI, the enzyme was chemically modified with dextran. The optimal activity of Dextran-ADI conjugates was determined at 0.08:20 M ratio of ADI: Dextran, with an overall increase to ADI molecular subunit mass to (similar to)100 kDa. ADI was conjugated with dextran via the a-amino groups interaction of surface lysine residues of ADI. The resistance of Dextran-ADI conjugate to proteolysis had been increased by 2.5 folds to proteinase K and trypsin, suggesting the shielding of > 50% of ADI surface proteolytic recognition sites. The native and Dextran-ADI conjugates have the same optimum reaction temperature (37 degrees C), reaction pH and pH stability (7.0-8.0) with dependency on K+ ions as a cofactor. Dextran-ADI conjugates exhibited a higher thermal stability by (similar to) 2 folds for all the tested temperatures, ensuring the acquired structural and catalytic stability upon dextran conjugation. Dextran conjugation slightly protect the reactive amino and thiols groups of surface amino acids of ADI from amino acids suicide inhibitors. The affinity of ADI was increased by 5.3 folds to free L-arginine with a dramatic reduction in citrullination of peptidylarginine residues upon dextran conjugation. The anticancer activity of ADI to breast (MCF-7), liver (HepG-2) and colon (HCTB, HT29, DLD1 and LS174 T) cancer cell lines was increased by 1.7 folds with dextran conjugation in vitro. Pharmacokinetically, the half-life time of ADI was increased by 1.7 folds upon dextran conjugation, in vivo. From the biochemical and hematological parameters, ADIs had no signs of toxicity to the experimental animals. In addition to the dramatic reduction of L-arginine in serum, citrulline level was increased by 2.5 folds upon dextran conjugation of ADI. This is first report exploring thermostable ADI from thermophilic A. nidulans with robust structural stability, catalytic efficiency and proteolytic resistance.
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