Autoimmune uveitis is a relapsing blind-causing ocular condition with complex pathogenesis that is not completely understood. There is a high demand for accurate animal models of experimental autoimmune uveitis (EAU) suitable for elucidating the molecular mechanisms of the disease and testing new therapeutic approaches. Here, we demonstrated that photoreceptor Ca2+/Zn2+-sensor protein recoverin is a uveoretinal antigen in albino rabbits provoking typical autoimmune chorioretinitis 2–4 weeks after immunization. The pathologic process in recoverin-induced EAU shared features with human disease and included lymphocytic infiltration of the retina, Dalen–Fuchs nodules and foci of subtotal or total retinal atrophy, manifested as a decrease in amplitude of the a-wave of the electroretinogram. In some cases, changes in the retinal vascular pattern and subretinal hemorrhages were also observed. These signs were accompanied by a gradual accumulation of serum antibodies against recoverin. Biochemical examination of the aqueous humor (AH) revealed typical characteristics of inflammation and oxidative stress, including increased levels of TNF-α and IL-6 and decreased levels of IL-10, as well as decreased total antioxidant activity, superoxide dismutase and glutathione peroxidase activities, and increased zinc concentration. Consistently, metabolomic and targeted lipidomic analysis of AH showed high lactate and low ascorbic acid levels in early EAU; increased levels of key pro-inflammatory signaling lipids such as PGE2, TXB2, 11-HETE and Lyso-PAF; and reduced levels of the anti-inflammatory fatty acid DHA in advanced stages of the disease. Uveitic AH became enriched with recoverin, confirming disruption of the blood–ocular barrier and photoreceptor damage. Notably, the application of mitochondria-targeted antioxidant therapy impeded EAU progression by maintaining local antioxidant activity and suppressing TNF-α, IL-6 and PGE2 signaling. Overall, our results demonstrate that recoverin-induced EAU in rabbits represents an accurate model of human autoimmune posterior uveitis and suggest new directions for its therapy that can be trialed using the developed model.
1 December 2017 in Russian Journal of Bioorganic Chemistry
The composition of terpen lactones and flavonol glycosides of commercial preparation series based on Ginkgo biloba extracts was investigated by 1H NMR spectroscopy. The content of individual terpen...
The roots and rhizomes of Rubia tinctorum L. have been widely used both for industrial and medicinal purposes for centuries. The primary biologically active substances from Rubia tinctorum L. roots and rhizomes are anthraquinone derivatives such as ruberythric acid and lucidin-3-primeveroside. Their identification and quantification are carried out by various analytical methods, requiring a complicated sample preparation as well as special reagents and reference samples. However, NMR spectroscopy has no limitations of this kind. In this work, we have developed and validated a new express and standard-free method for the qualitative and quantitative analysis of ruberythric acid and lucidin-3-primeveroside by 1H NMR spectroscopy in the extracts from the roots and rhizomes of Rubia tinctorum L. In this work, we have optimized the conditions of the sample preparation and registration of 1H NMR spectra, determined the optimal solvent and reference compound and confirmed the obtained results by HPLC-UV-MS.
Deuterium is a heavy nonradioactive isotope of hydrogen, present in ocean water at a concentration of around 150 parts per million (ppm). In terrestrial nature, deuterium content in water varies by at least a factor of two, while in industry and research, the whole range of deuterium concentrations is employed. Water with altered deuterium content is currently of increasing interest in biology and medicine. Therefore, accurate measurements of deuterium content in water are an important problem. Historically, such measurements have relied on densitometry and mass spectrometry. More recently, alternative techniques emerged, such as Fourier Transform Infrared (FTIR) spectroscopy, varieties of Laser Spectroscopy (LS), Off-Axis Integrated-Cavity Laser Spectroscopy (OA-ICOS), nuclear magnetic resonance (NMR) spectroscopy, original research developments based on two-dimensional diffuse laser scattering (2D-DLS), and isotopic fractionation in metalloorganic nanotubes (MONTs). This review aims to provide brief description of the techniques currently in use for measuring deuterium content in water, evaluate their analytical performance and applicability across different contexts, and discuss the broader implications of these measurements in scientific research.
ИДЕНТИФИКАЦИЯ ТЕРПЕНОВЫХ ЛАКТОНОВ И ФЛАВОНОГЛИКОЗИДОВ В ПРЕПАРАТАХ НА ОСНОВЕ ЭКСТРАКТА ГИНКГО БИЛОБА И НОВЫЙ СПОСОБ ПОЛУКОЛИЧЕСТВЕННОЙ ОЦЕНКИ СОДЕРЖАНИЯ ФЛАВОНОГЛИКОЗИДОВ МЕТОДОМ СПЕКТРОСКОПИИ ЯМР 1Н
Дигидрокверцетин (ДГК) — биофлавоноид, обладающий высокой антиоксидантной, капилляропротекторной и противовоспалительной активностью. Ранее ДГК применялся при инфекции, вызванной коронавирусом ближневосточного респираторного синдрома (MERS-CoV). В настоящее время ДГК рассматривается в качестве потенциального регулятора окислительного стресса в составе комплексной терапии COVID-19. ДГК характеризуется высоким профилем безопасности, но низкой биодоступностью, ограничива-ющей его применение. Для повышения биодоступности ДГК могут быть использованы инновационные технологии (липосомирование, инженерия кристаллов и др.).