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BioChem, Volume 4, Issue 1 (March 2024) – 3 articles

Cover Story (view full-size image): Muscle lactate dehydrogenase (LDH-A) catalyzes the reduction in pyruvate to lactate, the end product of anaerobic glycolysis. LDH-A is overexpressed in many cancers prior to and even when tumors receive adequate oxygen, and lactate has multiple cellular roles. Singlet oxygen and hypochlorous acid (HOCl) induced distinct patterns of protein crosslinks in LDH-A that were observed using SDS-PAGE under reducing conditions. LDH-A cysteines were oxidized via HOCl (only 1–10 equivalents over enzyme) but were resistant to H2O2, chloramines, and Angeli’s salt. HOCl oxidation inhibited LDH-A activity and yielded inter-chain disulfides observed using nonreducing SDS-PAGE. However, disulfide reduction did not restore LDH-A activity, which was lost due to HOCl oxidation. An irreversible conformational change induced via HOCl was detected using native gel electrophoresis and tryptophan fluorescence. View this paper
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24 pages, 3781 KiB  
Review
Flavonoids and Flavonoid-Based Nanoparticles for Osteoarthritis and Rheumatoid Arthritis Management
by Hicham Wahnou, Youness Limami and Mounia Oudghiri
BioChem 2024, 4(1), 38-61; https://doi.org/10.3390/biochem4010003 - 13 Mar 2024
Cited by 1 | Viewed by 1162
Abstract
Arthritis, a global health burden comprising osteoarthritis and rheumatoid arthritis, demands advanced therapeutic approaches. In this context, flavonoids, a diverse group of naturally occurring compounds abundant in fruits, vegetables, and medicinal plants, have emerged as promising candidates for mitigating the inflammatory processes associated [...] Read more.
Arthritis, a global health burden comprising osteoarthritis and rheumatoid arthritis, demands advanced therapeutic approaches. In this context, flavonoids, a diverse group of naturally occurring compounds abundant in fruits, vegetables, and medicinal plants, have emerged as promising candidates for mitigating the inflammatory processes associated with arthritic conditions. This review aims, first, to provide a comprehensive exploration of the potential of flavonoids, focusing on specific compounds such as quercetin, epigallocatechin-3-gallate (EGCG), apigenin, luteolin, fisetin, silibinin, kaempferol, naringenin, and myricetin. The second section of this review delves into the anti-arthritic activities of these flavonoids, drawing insights from clinical trials and scientific studies. Each flavonoid is scrutinized individually to elucidate its mechanisms of action and therapeutic efficacy in the context of both osteoarthritis and rheumatoid arthritis. The third section of this review highlights the challenges associated with harnessing flavonoids for anti-inflammatory purposes. Bioavailability limitations pose a significant hurdle, prompting the exploration of innovative strategies such as the use of nanoparticles as delivery vehicles. In response to these challenges, the fourth section focuses on the emerging field of flavonoid-based nanoparticles. This includes detailed discussions on quercetin, EGCG, fisetin, and naringenin-based nanoparticles, highlighting formulation strategies and preclinical evidence supporting their potential in arthritis management. The targeted delivery to inflammatory sites and the exploration of synergistic combinations with other compounds are also discussed as promising avenues to enhance the therapeutic impact of flavonoids. This review consolidates current knowledge on flavonoids and their nanoformulations as potential therapeutic interventions for osteoarthritis and rheumatoid arthritis. By addressing challenges and presenting future research directions, this review aims to contribute to the advancement of innovative and effective strategies for alleviating the global burden of arthritis. Full article
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20 pages, 2808 KiB  
Article
Inhibition of Lactate Dehydrogenase-A by Singlet Oxygen and Hypochlorous Acid via Cysteine Oxidation and Irreversible Conformational Changes
by Lisa Landino, Lydia Boike and Taylor Lain
BioChem 2024, 4(1), 18-37; https://doi.org/10.3390/biochem4010002 - 2 Feb 2024
Viewed by 1254
Abstract
Muscle lactate dehydrogenase (LDH-A) catalyzes the reduction of pyruvate to lactate, the end product of anaerobic glycolysis. LDH-A is overexpressed in many cancers prior to and even when tumors receive adequate oxygen, and lactate has multiple cellular roles. We assessed the effect of [...] Read more.
Muscle lactate dehydrogenase (LDH-A) catalyzes the reduction of pyruvate to lactate, the end product of anaerobic glycolysis. LDH-A is overexpressed in many cancers prior to and even when tumors receive adequate oxygen, and lactate has multiple cellular roles. We assessed the effect of singlet oxygen and hypochlorous acid (HOCl) on mammalian LDH-A. Oxidants induced distinct patterns of protein crosslinks observed by SDS-PAGE under reducing conditions. LDH-A cysteines were detected using fluorescein-modified maleimide to assess their oxidation and accessibility. Singlet oxygen initially increased cysteine exposure, but higher doses resulted in their oxidation in addition to non-reducible covalent crosslinks. LDH-A cysteines were oxidized by micromolar HOCl (1–10 equivalents over enzyme) but were resistant to millimolar H2O2, chloramines and Angeli’s salt. HOCl oxidation inhibited LDH-A activity and yielded inter-chain disulfides observed by nonreducing SDS-PAGE. Disulfide reduction did not restore LDH-A activity that was lost due to HOCl oxidation. An irreversible conformational change induced by HOCl was detected by native gel electrophoresis and tryptophan fluorescence. In the absence of pyruvate, LDH-A enhanced NADH oxidation resulting in H2O2 formation. Singlet oxygen, but not HOCl, initiated this superoxide-dependent chain reaction. Once damaged by both singlet oxygen or HOCl, LDH-A had decreased NADH oxidation activity. Full article
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17 pages, 9817 KiB  
Article
Electrospun Polyurethane Vascular Grafts for Cerebral Revascularization: A Pilot Study on Rats
by Evelynn Vergauwen, Michiel R. L. Tubeeckx, Annemie Houben, Sandra Van Vlierberghe, Marc Demolder, Guido R. Y. De Meyer, Patrick Pauwels and Tomas Menovsky
BioChem 2024, 4(1), 1-17; https://doi.org/10.3390/biochem4010001 - 5 Jan 2024
Viewed by 948
Abstract
The current standard technique for vascular grafting in cerebral revascularization surgery employs the interposition of an autologous blood vessel. Technical complications have necessitated the development of a synthetic alternative, but classical biomaterials are not suited for small caliber vascular grafting due to the [...] Read more.
The current standard technique for vascular grafting in cerebral revascularization surgery employs the interposition of an autologous blood vessel. Technical complications have necessitated the development of a synthetic alternative, but classical biomaterials are not suited for small caliber vascular grafting due to the resulting neointimal hyperplasia and thrombosis. The electrospinning of polymers is a promising technique for the development of small vascular grafts. The in vivo performance and efficacy of electrospun polyurethane (ePU) grafts with an internal diameter of <1.5 mm have thus far not been evaluated. We developed a novel ePU graft, with a diameter of 1.25 mm, for implantation into the infrarenal aorta of rats. The patency rates of grafts after a 4-month period were equal to those reported in other studies using larger ePU graft diameters and equal or higher than in studies employing other biomaterials. We observed some loss in flow velocity throughout the grafts, which suggests a decreased elasticity of the graft compared to that of the native rat aorta. However, the grafts demonstrated good neo-endothelialization and minimal neointimal hyperplasia. Their porosity promoted cellular infiltration, as observed under tissue slide examination. Our results show that ePU vascular grafts with an internal diameter of <1.5 mm are promising candidates for vascular grafting in cerebral revascularization surgery. Full article
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