Central Angiotensin II Stimulation Promotes β Amyloid Production in Sprague Dawley Rats

BACKGROUND: Stress and various stress hormones, including catecholamines and glucocorticoids, have recently been implicated in the pathogenesis of Alzheimer's disease (AD), which represents the greatest unresolved medical challenge in neurology. Angiotensin receptor blockers have shown benefits in AD and prone-to-AD animals. However, the mechanisms responsible for their efficacy remain unknown, and no studies have directly addressed the role of central angiotensin II (Ang II), a fundamental stress hormone, in the pathogenesis of AD. The present study focused on the role of central Ang II in amyloidogenesis, the critical process in AD neuropathology, and aimed to provide direct evidence for the role of this stress hormone in the pathogenesis of AD. METHODOLOGY/PRINCIPAL FINDINGS: Increased central Ang II levels during stress response were modeled by intracerebroventricular (ICV) administration of graded doses of Ang II (6 ng/hr low dose, 60 ng/hr medium dose, and 600 ng/hr high dose, all delivered at a rate of 0.25 µl/hr) to male Sprague Dawley rats (280-310 g) via osmotic pumps. After 1 week of continuous Ang II infusion, the stimulation of Ang II type 1 receptors was accompanied by the modulation of amyloid precursor protein, α-, β-and γ-secretase, and increased β amyloid production. These effects could be completely abolished by concomitant ICV infusion of losartan, indicating that central Ang II played a causative role in these alterations. CONCLUSIONS/SIGNIFICANCE: Central Ang II is essential to the stress response, and the results of this study suggest that increased central Ang II levels play an important role in amyloidogenesis during stress, and that central Ang II-directed stress prevention and treatment might represent a novel anti-AD strategy

Design Principle and Development Trends of Silicon-Based Anode Binders for Lithium-ion Batteries: A Mini Review

Abstract: Silicon (Si), recognized as a promising alternative material for the anodes of lithium-ion batteries, boasts a high theoretical specific capacity and abundant natural availability. During the preparation of silicon-based anodes, binders play a pivotal role in ensuring the cohesion of silicon particles, conductive agents, and current collectors. The structure and performance of these binders are critical for the mechanical stability, electrical conductivity, and stress dissipation capacity of the anodes. This review initially outlines the structural characteristics of various binders, including linear, branched, and three-dimensional cross-linked types. It then delves into the relationship between the structure and properties of these binders in the context of their application in high-performance lithium-ion batteries, focusing on their mechanical properties, electrical conductivity, and self-healing capabilities. Particular attention is given to the design strategies for binders that facilitate stress dissipation, with an emphasis on integrating multifunctional polymer binders renowned for their superior conductive and self-healing features. Such binders contribute to the formation of a robust three-dimensional network structure via multiple bonding mechanisms, including chemical, non-covalent, and coordination interactions. This configuration significantly enhances the adhesion between silicon particles, thereby facilitating the efficient dissipation of stress, which is a key aspect for ensuring the long-term cycling stability of lithium-ion batteries. Lastly, the paper explores future development directions for silicon anode binders, advocating for a thorough investigation into the synergy of diverse structural and functional combinations, with the aim of advancing the performance and practical application of silicon-based lithium-ion batteries

Bioactive Components from Ginger, Tea and Apple Prevent Protein Glycation by Trapping Methylglyoxal with Potential in Alleviation of Diabetic Complications

Diabetes is the fifth-deadliest disease in the United States. Most diabetes patients die from diabetic complications, such as renal failure, heart attack or stroke. However, diabetic complications are still neither preventable nor curable. New strategies that can prevent, treat, or cure diabetic complications are needed. Increasing evidence has identified the formation of advanced glycation end products (AGEs) as a major pathogenic link between hyperglycemia and diabetes-related complications. In diabetes, formation of AGEs occurs at a higher rate when compared to non-diabetic normal individuals. Alpha-oxoaldehydes such as methylglyoxal (MGO) and glyoxal (GO), the reactive dicarbonyl intermediates generated during the non-enzymatic glycation between reducing sugars and amino groups of proteins, lipids, and DNA, are precursors of AGEs and exert direct toxicity to cells and tissues. Levels of MGO and GO were observed to be 2-6 times higher in diabetic patients' plasma as compared with healthy people's plasma. In addition, this is complicated by many food products and beverages representing exogenous sources of MGO and GO. It is likely that decreasing the levels of MGO and GO and inhibiting the formation of AGEs will form an important component of future therapy in patients with diabetes. Numerous studies have reported that bioactive components in ginger, tea and apple can prevent diabetes and its related complications. However, the underlying molecular mechanisms are still largely unknown. In this project, we investigated the effect of bioactive compounds in ginger ([6]-shogaol (6S) and [6]-gingerol (6G)), tea (epigallocatechin gallate (EGCG)) and apple (phloretin and phloridzin) to inhibit the formation of AGEs via trapping MGO. We demonstrated for the first time that both [6]-shogaol (6S) and [6]-gingerol (6G), the major active components in ginger, markedly trapped MGO in vitro and consequently formed mono-MGO adducts, 6S-MGO and 6G-MGO, which were purified from the respective chemical reaction and characterized as novel compounds by NMR experiments and LC-MS/MS approaches. We revealed that the ?-carbon of carbonyl group in the side chain of 6S or 6G is the major active site for trapping MGO. We also demonstrated that 6S and 6G could effectively inhibit the formation of MGO-induced AGEs via trapping MGO in a time-dependent manner in the human serum albumin (HSA)-MGO system. Mono-MGO adducts, 6S-MGO and 6G-MGO, were determined to be the major conjugates in 6S- and 6G-treated HSA-MGO assays, respectively, using LC-ESI/MS techniques. These findings showed the potential effects of 6S and 6G on the prevention of protein glycation, suggesting regular consumption of ginger root extract may attenuate the progression of MGO-associated diabetic complications in patients. Similarly, we found that both EGCG and phloretin could inhibit the formation of AGEs through the same pathways. In addition, we also studied whether these compounds could inhibit the formation of AGEs via trapping MGO in high fat diet treated mice. Two different doses of 6G, EGCG and phloretin (25 mg/kg and 75 mg/kg) were given to mice through oral gavage for 16 weeks. Plasma and tissue samples were collected from control and treated mice. The formation of MGO adducts of each compound were analyzed using our established LC/MS methods. The levels of MGO and AGEs were also quantified.qscienc

THE PREVENTIVE EFFECT AND ENHANCE IMMUNITY FUNCTION OF BU-ZHONG-YI-QIWAN ON S180 TUMOR MICE.

Background: To evaluate the preventive effect and enhance immunity functions of Bu-zhong-yi-qi wan in vivo. Materials and Methods: S180 tumor mice model was established by subcutaneous injection a dose of 0.2 ml (1×107/ml) at the right oxter. The inhibitory rates, spleen indexes and thymus indexes were calculated. Splenic lymphocyte proliferative activity assay and phagocytosis activity of peritoneal macrophages were done. Interferon (IFN-γ), interleukin (IL-2) and tumor necrotic factor (TNF-α) in serum were detected. Results: In the S180 tumor-bearing mice, Bu-zhong-yi-qi wan with medium-dose (975 mg/kg, 100 mg/l) had potent preventive effect and anti-tumor effect, macrophage phagocytosis and Con A-stimulated splenocyte proliferation were increased as compared with model control treatment. Bu-zhong-yi-qi wan could take part in the immune response by promoting the proliferation and differentiation of Tcells, increasing the activity of the macrophages, inducing the generation of cell factor IL-2, TNF-α, IFN-γ. Conclusion: It proved that Bu-zhong-yi-qi wan of medium-dose had great preventive effect and could enhance immunity function

Comparison of the gut microbiota and untargeted gut tissue metabolome of Chinese mitten crabs (Eriocheir sinensis) with different shell colors

IntroductionThe Chinese mitten crab (Eriocheir sinensis) is a highly valued freshwater crustacean in China. While the natural shell color of E. sinensis is greenish brown (GH), we found a variety with a brownish-orange shell color (RH). Although RH is more expensive, it exhibits a lower molting frequency and growth rate compared with GH, which significantly reduces its yield and hinders large-scale farming. The growth and development of animals are closely related to their gut microbiota and gut tissue metabolic profiles.MethodsIn this study, we compared the gut microbiome communities and metabolic profiles of juvenile RH and GH crabs using 16S rRNA gene sequencing and liquid chromatography–mass spectrometry (LC–MS), respectively.ResultsOur findings indicated that the intestinal microbial composition and metabolic characteristics of E. sinensis differed significantly between RH and GH. At the operational taxonomic unit (OTU) level, the α-diversity of the gut microbiota did not differ significantly between RH and GH, while the β-diversity of the RH gut microbiota was higher than that of the GH gut microbiota. At the species level, the richness of unclassified_c_Alphaproteobacteria was significantly higher in the GH group, while the RH group had a significantly higher richness of three low-abundance species, Flavobacteria bacterium BAL38, Paraburkholderia ferrariae, and uncultured_bacterium_g__Legionella. In the current study, 598 gut tissue metabolites were identified, and 159 metabolites were significantly different between GH and RH. The metabolite profile of RH was characteristic of a low level of most amino acids and lipid metabolites and a high level of several pigments compared with that of GH. These metabolites were enriched in 102 KEGG pathways. Four pathways, including (1) Central carbon metabolism in cancer, (2) protein digestion and absorption, (3) alanine, aspartate and glutamate metabolism, and (4) aminoacyl-tRNA biosynthesis, were significantly enriched. The correlation analysis between metabolites and microbiotas indicated that most key differential metabolites were positively correlated with the abundance of Shewanella_sp_MR-7.DiscussionThis research provided a greater understanding of the physiological conditions of E. sinensis varieties with different shell colors by comparing the gut microbiota and gut tissue metabolome