Bifidobacterium adolescentis Alleviates Liver Steatosis and Steatohepatitis by Increasing Fibroblast Growth Factor 21 Sensitivity

The gut microbiota is a newly identified contributor to the development of non-alcoholic fatty liver disease (NAFLD). Previous studies of Bifidobacterium adolescentis (B. adolescentis), a species of Bifidobacterium that is common in the human intestinal tract, have demonstrated that it can alleviate liver steatosis and steatohepatitis. Fibroblast growth factor 21 (FGF21) has long been considered as a biomarker of NAFLD, and recent studies have shown the protective effect of FGF21 analogs on NAFLD. We wondered whether B. adolescentis treatment would alleviate NAFLD via the interaction with FGF21. To this end, male C57BL/6J mice on a choline-deficient high-fat diet (CDHFD) were treated with drinking water supplemented with B. adolescentis for 8 weeks, followed by the acute administration of recombinant mouse FGF21 protein (rmFGF21) to conduct the FGF21 response test. Consistent with previous studies, B. adolescentis supplementation reversed the CDHFD-induced liver steatosis and steatohepatitis. This was evaluated on the NAFLD activity score (NAS), reduced liver enzymes, and lipid accumulation. Further studies demonstrated that B. adolescentis supplementation preserved the gut barrier, reduced the gut microbiota-derived lipopolysaccharide (LPS), and inhibited the hepatic TLR4/NF-κB pathway. This was accompanied by the elevated expressions of the receptors of FGF21, fibroblast growth factor receptor 1 (FGFR1) and β-klotho (KLB), in the liver and the decreased expression of FGF21. The results of FGF21 response test showed that B. adolescentis supplementation alleviated the CDHFD-induced FGF21 resistance. In vivo experiments suggested that LPS could suppress the expression of FGF21 and KLB in a dose-dependent manner. Collectively, this study showed that B. adolescentis supplementation could alleviate NAFLD by increasing FGF21 sensitivity.

Behavioral response and erythrocyte chromophilia of rats in experimental traumatic brain injury

Введение. Патогенетические основы изменения микроциркуляции крови в головном мозге вследствие черепно-мозговой травмы (ЧМТ) изучены не в полной мере по причине высокой инвазивности нейроморфологических методов. Цель исследования - изучение поведенческого статуса и информативности цитохимических критериев хромофилии эритроцитов в качестве маркеров вазореактивности микрососудов головного мозга при черепно-мозговой травме у крыс. Методика. Объектом исследования являлись 3-месячные аутбредные крысы Wistar массой 250-270 г. Легкую и средней тяжести ЧМТ воспроизводили с применением модифицированной модели падающего груза для взрослых крыс. Через 2 ч, 1, 2, 8 и 14 сут после моделирования ЧМТ проводили неврологическое обследование животных по модифицированной шкале Neurological Severity Scores (mNSS), сенсомоторное - по степени тревожности в тесте «свет-темнота», поведение анализировали с использованием теста условной реакции пассивного избегания. С помощью хромаффинной реакции исследовали функциональное состояние эритроцитов. Срезы тканей головного мозга, окрашивали по Нисслю и гематоксилин-эозином, микроскопировали, проводили морфометрию цифровых изображений. Результаты. Неврологическое обследование при среднетяжелой ЧМТ показало очаговую симптоматику, соответствующую выраженным неврологическим расстройствам, тогда как после ЧМТ легкой степени у крыс отмечались незначительные нарушения координации. В тесте условной реакции пассивного избегания на 7-е сут у этих животных выявлено состояние повышенной тревожности. Морфометрический анализ препаратов головного мозга травмированных животных показал уменьшение диаметра просвета капилляров и выявил признаки гипоксии нейронов. Цитохимическая оценка эритроцитов, с привлечением количественного определения степени флуоресценции, выявила особенности окислительного метаболизма в клетках у травмированных крыс. Эти показатели коррелировали с морфологическими признаками гипоксии головного мозга. Заключение. В начальный посттравматический период отмечено уменьшение диаметра просвета капилляров нервной ткани, наличие морфологических признаков компенсации нейронов, что является локальной ответной реакцией клеток на ишемию головного мозга. В капиллярах определяется нарушение гемореологии, что является следствием изменения окислительно-восстановительных процессов вследствие гипоксии при внутричерепной травме. The pathogenetic basis of changes in blood microcirculation in the brain due to traumatic brain injury (TBI) has not been fully studied due to the highly invasive nature of neuromorphological methods. Aim: To study the behavioral status and informative value of cytochemical criteria for erythrocyte chromophilia as markers of cerebral microvessel vasoreactivity in rats with TBI. Methods. The study was conducted on 3-month-old Wistar albino, outbred rats weighing 250-270 g. Mild to moderate TBI was simulated using a modified falling weight model for adult rats. At 2 hrs, 1, 2, 8, and 14 days after TBI, a neurological examination was performed according to the modified Neurological Severity Score (mNSS) modified scale and a sensorimotor examination was performed according to the degree of anxiety in the light-dark test. Behavior was analyzed using the conditioned passive avoidance response test. The functional state of erythrocytes was studied using the chromaffin reaction. Brain tissue samples stained by Nissl and with hematoxylin-eosin were evaluated under a microscope, digital images were obtained, and morphometric processing was performed. Results. Neurological examination after moderate TBI showed focal symptoms corresponding to severe neurological disorders, while after mild TBI, rats had minor coordination disorders. In the conditioned passive avoidance response test on the 7th day, the rats showed a state of increased anxiety. Morphometric analysis of the brains showed a decrease in the diameter of capillary lumen and changes in neurons, indicating signs of hypoxia. The cytochemical assessment of erythrocytes, involving a quantitative determination of the degree of fluorescence, revealed features of cell oxidative metabolism in injured rats. Moreover, these indicators correlated with morphological signs of hypoxia in brain neural tissue. Conclusion. In the initial post-traumatic period, there was a decrease in the capillary lumen diameter of the brain neural tissue and the presence of morphological signs of neuronal compensation, which is a local response of cells to cerebral ischemia. Disorders of hemorheology were found. These changes were a consequence of altered redox processes due to hypoxia after intracranial injury.

Digital comics learning media for high school on the human excretory system concept

Based on the preliminary analysis, one of the things needed in learning is a learning media that describes the material clearly, briefly, easily understood, and fulfills offline and online learning. This research aims to develop a digital comic learning media on the concept of the human excretory system. This study uses the R&D (Research and Development) method with the ADDIE model. The instruments in this study include a validation questionnaire, practicality test sheets, readability questionnaire, and student response questionnaire sheets to the developed digital comic learning media. The research data were analyzed quantitatively by calculating the percentage. The results showed that the digital comics learning media was valid and feasible to be used as learning media (combined average of 83%). The results of the student response test showed a very good response to the digital comic learning media with a percentage of 84%