Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function.

Background: Integrity of the tight junction (TJ) which seals the gap between the epithelial cells of the gastrointestinal tract is critical in preventing the entry of the microbial toxins, antigens, and other harmful products in the subepithelial tissues and the internal milieu. By enabling the absorption of these products, impairment of the intestinal epithelial barrier leads to local and systemic inflammation. We have recently found depletion of the key protein constituents of colonic epithelial TJ in animals with chronic kidney disease (CKD). Postmortem studies have revealed the presence of inflammation throughout the gastrointestinal tract in uremic humans. This observation suggests that uremia may cause disruption of the epithelial barrier in all segments of the gastrointestinal tract including the stomach, jejunum, and ileum. The present study was undertaken to explore this possibility. Methods: Sprague-Dawley rats were randomized to CKD or control groups. The CKD group was subjected to 5/6 nephrectomy while the control group underwent a sham operation. The animals were observed for 10 weeks at which time they were euthanized and their stomachs, jejunums, and ileums were removed and processed for measurement of TJ proteins. Results: The CKD rats showed marked azotemia, systemic oxidative stress, and marked depletion of the key protein constituents of the epithelial TJ (claudin-1, occludin, and ZO1) in the stomach, jejunum, and ileum. Conclusions: The present study extends the earlier finding of uremia-induced disruption of colonic epithelial TJ by documenting the involvement of the stomach, jejunum, and ileum as well.

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End-to-end neural dialogue generation has shown promising results recently, but it does not employ knowledge to guide the generation and hence tends to generate short, general, and meaningless responses. In this paper, we propose a neural knowledge diffusion (NKD) model to introduce knowledge into dialogue generation. This method can not only match the relevant facts for the input utterance but diffuse them to similar entities. With the help of facts matching and entity diffusion, the neural dialogue generation is augmented with the ability of convergent and divergent thinking over the knowledge base. Our empirical study on a real-world dataset proves that our model is capable of generating meaningful, diverse and natural responses for both factoid-questions and knowledge grounded chi-chats. The experiment results also show that our model outperforms competitive baseline models significantly.

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Silicon nanoparticles ranging from 2 to 16 nm were synthesized by a facile wet chemical route, in which SiO amorphous powder was annealed at 1000 °C, etched in hydrofluoric acid, and surface modified by alkene. After alkyl-termination of the particle surfaces, size selective precipitation technique was applied to separate the nanoparticles into uniform sized fractions. Transmission electron microscopy showed well-dispersed and highly crystalline silicon nanoparticles after the treatment by alkene. Visible room-temperature photoluminescence in the range 800−500 nm was observed from these nanoparticles. The photoluminescence intensity has significantly been enhanced by the surface functionalization. Moreover, the PL peak energy of the size-selected nanoparticles shifted to blue as the size decreased due to quantum confinement effect. The experimental result was also compared with the theoretical predictions and was found to follow the general trend of the model calculations.

Background: Chronic kidney disease (CKD) impairs intestinal barrier function which by allowing influx of noxious products causes systemic inflammation. We have recently shown that intestinal barrier dysfunction in CKD is due to degradation of epithelial tight junction (TJ) which is, in part, mediated by influx of urea and its conversion to ammonia by microbial urease. We hypothesized that by adsorbing urea and urea-derived ammonia, oral activated charcoal (AST-120) may ameliorate CKD-induced intestinal epithelial barrier disruption and systemic inflammation. Methods: Rats were randomized to the CKD or control groups. The CKD group was fed a chow containing 0.7% adenine for 2 weeks. They were then randomized to receive a chow with or without AST-120 (4 g/kg/day) for 2 weeks. Rats consuming regular diet served as controls. Animals were then euthanized, colons were removed and processed for Western blot and immunohistology, and plasma was used to measure endotoxin and oxidative and inflammatory markers. Results: Compared with the controls, the untreated CKD rats showed elevated plasma endotoxin, IL-6, TNF-α, MCP-1, CINC-3, L-selectin, ICAM-1, and malondialdehyde, and depletions of colonic epithelial TJ proteins, claudin-1, occludin, and ZO1.Administrationof AST-120 resulted in partial restoration of the epithelial TJ proteins and reduction in plasma endotoxin and markers of oxidative stress and inflammation. Conclusions: CKD animals exhibited depletion of the key protein constituents of the colonic epithelial TJ which was associated with systemic inflammation, oxidative stress and endotoxemia. Administration of AST-120 attenuated uremia-induced disruption of colonic epithelial TJ and the associated endotoxemia, oxidative stress and inflammation.

Background Gut inflammation is prevalent in chronic kidney disease (CKD) and likely contributes to systemic inflammation via disruption of the epithelial tight junction with subsequent endotoxin and bacterial translocation. Aims To study the expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls, and demonstrate the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent Nrf2 activator. Methods CKD was induced via 5/6 nephrectomy in Sprague-Dawley rats, and dh404 (2 mg/kg/day) was used to study the effects of systemic Nrf2 activation. The experimental groups included sham, CKD and CKD? dh404 rats. Blood and colon tissues were analyzed after a 10-week study period. Results Colon from CKD rats showed histological evidence of colitis, depletion of epithelial tight junction proteins, significant reduction of Nrf2 and its measured target gene products (NQO1, catalase, and CuZn SOD), activation of NFkB, and upregulation of pro-inflammatory molecules (COX-2, MCP-1, iNOS, and gp91 phox ). Treatment with dh404 attenuated colonic inflammation, restored Nrf2 activity and levels of NQO1, catalase and CuZn SOD, decreased NFkB and lowered expression of COX-2, MCP-1, iNOS, and gp91 phox . This was associated with restoration of colonic epithelial tight junction proteins (occludin and claudin-1). Conclusions CKD rats exhibited colitis, disruption of colonic epithelial tight junction, activation of inflammatory mediators, and impairment of Nrf2 pathway. Treatment with an Nrf2 activator restored Nrf2 activity, attenuated colonic inflammation, and restored epithelial tight junction proteins.