Exosomal miR-29b of Gut Origin in Patients With Ulcerative Colitis Suppresses Heart Brain-Derived Neurotrophic Factor.

Background and Aims: While the interplay between heart and gut in inflammatory bowel disease (IBD) has previously been noted, how the inflamed gut impairs heart function remain elusive. We hypothesized that exosomal miRNAs of gut origin induce cardiac remodeling in IBD. Our aim was to identify plasma exosomal miRNAs that not only are of diagnostic value but also contribute to cardiac remodeling in patients with ulcerative colitis (UC). Methods: Plasma exosomes were isolated from UC patients and healthy control subjects and exosomal miRNAs were profiled by next-generation sequencing. Exosomal miR-29b levels in CCD841 CoN colon epithelial cells were detected by RT-qPCR. Exosomes packaged with miR-29b were incubated with H9c2 cells or administered to live mice. Results: The plasma exosomal miRNA profiles of the UC patients were significantly different from that of the controls and 20 miRNAs including miR-29b were differentially expressed. In CCD841 CoN cells, TNFα, IL-1ß, and H2O2 significantly elevated miR-29b in both the cells and their secreted exosomes (p < 0.01), suggesting that intestinal epithelium secrets exosomes rich in miR-29b in IBD. In H9c2 myoblast cells, miR-29b modulated multiple genes including brain-derived neurotrophic factor (BDNF). Epithelial cell-derived exosomes packaged with miR-29b also attenuated BDNF and increased cleaved caspase 3, suggestive of apoptosis. Furthermore, tail vein injection of engineered exosomes with high levels of miR-29b suppressed BDNF and augmented cleaved caspase 3 in the heart of adult mouse (p < 0.01). Conclusion: Plasma exosomal miRNA profile could be a novel diagnostic approach for IBD. Excessive plasma exosomal miR-29b suppresses critical proteins like BDNF in IBD, leading to cardiac impairment.

Electroacupuncture Regularizes Gastric Contraction and Reduces Apoptosis of Interstitial Cells of Cajal in Diabetic Rats.

BACKGROUND/AIMS: Gastric dysmotility is a frequent complication among patients with diabetes mellitus. Electroacupuncture (EA) has been empirically used to relieve gastrointestinal symptoms. The aims of this study were to investigate the effects of EA on gastric contraction and the mechanisms of interstitial cells of Cajal (ICC) involved. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomized into the normal control, diabetes (DM), diabetic and sham EA (DM + SEA), diabetic and low-frequency EA (DM + LEA), and diabetic and high-frequency EA (DM + HEA) groups. Diabetic models were established and then treated with EA for 8 weeks. Body weight and blood glucose were recorded every 2 weeks. The spontaneous contractions of distal gastric strips were analyzed. Immunostaining and RT-PCR were used to test the apoptotic ICC, IGF-1/IGF-1R, and Nrf2/HO-1 pathways. RESULTS: The body weight in the DM + LEA and DM + HEA groups were increased compared with that of the DM group, though there was no effect on the blood glucose. The gastric contractions were obviously disordered in the DM group, but EA could regularize the contractions. The number of apoptotic ICC was dramatically increased in the DM group, but reduced with EA treatment. Meanwhile, the IGF-1/IGF-1R pathway was verified to be significantly altered in diabetic rats. The Nrf2/HO-1 pathway was not significantly increased in the DM group. EA with different frequencies efficiently improved the expression of IGF-1/IGF-1R signaling and activated the Nrf2/HO-1 pathway. CONCLUSION: EA could improve gastric motility dysfunction and attenuate ICC apoptosis possibly through the regulation of IGF-1/IGF-1R and Nrf2/HO-1 pathways. EA may be a potential therapeutic method for diabetic gastric motility dysfunction.

Gastric Electrical Pacing Reduces Apoptosis of Interstitial Cells of Cajal via Antioxidative Stress Effect Attributing to Phenotypic Polarization of M2 Macrophages in Diabetic Rats.

BACKGROUND: Gastric electrical pacing (GEP) could restore interstitial cells of Cajal in diabetic rats. M2 macrophages contribute to the repair of interstitial cells of Cajal injury though secreting heme oxygenase-1 (HO-1). The aim of the study is to investigate the effects and mechanisms of gastric electrical pacing on M2 macrophages in diabetic models. METHODS: Sixty male Sprague-Dawley rats were randomized into control, diabetic (DM), diabetic with the sham GEP (DM+SGEP), diabetic with GEP1 (5.5 cpm, 100 ms, 4 mA) (DM+GEP1), diabetic with GEP2 (5.5 cpm, 300 ms, 4 mA) (DM+GEP2), and diabetic with GEP3 (5.5 cpm, 550 ms, 4 mA) (DM+GEP3) groups. The apoptosis of interstitial cells of Cajal and the expression of macrophages were detected by immunofluorescence technique. The expression levels of the Nrf2/HO-1 and NF-κB pathway were evaluated using western blot analysis or immunohistochemical method. Malonaldehyde, superoxide dismutase, and reactive oxygen species were tested to reflect the level of oxidative stress. RESULTS: Apoptosis of interstitial cells of Cajal was increased in the DM group but significantly decreased in the DM+GEP groups. The total number of macrophages was almost the same in each group. In the DM group, M1 macrophages were increased and M2 macrophages were decreased. However, M2 macrophages were dramatically increased and M1 macrophages were reduced in the DM+GEP groups. Gastric electrical pacing improved the Nrf2/HO-1 pathway and downregulated the phosphorylation of NF-κB. In the DM group, the levels of malonaldehyde and reactive oxygen species were elevated and superoxide dismutase was lowered, while gastric electrical pacing reduced the levels of malonaldehyde and reactive oxygen species and improved superoxide dismutase. CONCLUSION: Gastric electrical pacing reduces apoptosis of interstitial cells of Cajal though promoting M2 macrophages polarization to play an antioxidative stress effect in diabetic rats, which associates with the activated Nrf2/HO-1 pathway and the phosphorylation of NF-κB pathway.

Study on the jarosite mediated by bioleaching of pyrrhotite using Acidthiobacillus ferrooxidans / Estudo sobre a jarosita mediada pela biolixiviação da pirrotita usando Acidithiobacillus ferrooxidans

Precipitation of jarosite is a very important phenomenon that is observed in the bioleaching of pyrrhotite by Acidthiobacillus ferrooxidans (A. ferrooxidans). Jarosite is a major secondary mineral formed in acid supergene environment by oxidation of metal sulphide. The formation of jarosite could decrease leached percentage. The Eh-pH diagram of FeS1.12-H2O showed that the thermodynamic parameters of the jarosite were exists steadily on Eh=360 ～ 800, pH=2.8 ～ 5, and the results of pH condition test is consonant with the conclusions of thermodynamic analysis. By means of XRD and SEM, it could indicate that full propagation of A. ferrooxidans in the solution is beneficial to the formation of jarosite and jarosite mediated by bacterial has a better crystalline form than that synthesized by chemical method. This study indicates that pH value and ferrous/ferric iron concentration are key factors affecting the formation of jarosite. Leached percentage is higher when frequency was set more than 2.0. It is crucial to minimize jarosite formation in order to increase factory's efficiency.

A precipitação de jarosite é um fenômeno muito importante que é observado na biolixiviação da pirrotita por Acidithiobacillus ferrooxidans (A. ferrooxidans). A jarosita é um mineral secundário principal formado no ambiente supergênico ácido pela oxidação do sulfureto do metal. A formação de jarosite pode diminuir a porcentagem de lixiviação. O diagrama de Eh-pH de FeS1.12-H2O mostrou que os parâmetros termodinâmicos da jarosite estavam firmemente presentes em Eh = 360~800, pH = 2.8~5, e os resultados do teste de condição de pH estão em consonância com as conclusões da análise termodinâmica. Por meio de XRD e SEM, pode ser indicado que a propagação completa de A. ferrooxidans na solução é benéfica para a formação de jarosite e jarosite mediada por bactérias tem uma forma cristalina melhor do que a sintetizada por método químico. Este estudo indica que o valor do pH e a concentração de ferro ferroso/férrico são fatores chave que afetam a formação de jarosite. A porcentagem de lixiviação é maior quando a freqüência foi ajustada a mais de 2,0. É crucial para minimizar a formação de jarosite, a fim de aumentar a eficiência da fábrica.