Oxidative stress contributes to the pathogenesis of diabetic nephropathy (DN). Nuclear factor erythroid 2-related factor 2 (NRF2) plays a key role in cellular defense against oxidative stress. NRF2 activators have shown promising preventive effects on DN. Sodium butyrate (NaB) is a known activator of NRF2. However, it is unknown whether NRF2 is required for NaB protection against DN. Therefore, streptozotocin-induced diabetic C57BL/6 Nrf2 knockout and their wild-type mice were treated in the presence or absence of NaB for 20 weeks. Diabetic mice, but not NaB-treated diabetic mice, developed significant renal oxidative damage, inflammation, apoptosis, fibrosis, pathological changes and albuminuria. NaB inhibited histone deacetylase (HDAC) activity and elevated the expression of Nrf2 and its downstream targets heme oxygenase 1 and NAD(P)H dehydrogenase quinone 1. Notably, deletion of the Nrf2 gene completely abolished NaB activation of NRF2 signaling and protection against diabetes-induced renal injury. Interestingly, the expression of Kelch-like ECH-associated protein 1, the negative regulator of NRF2, was not altered by NaB under both diabetic and non-diabetic conditions. Moreover, NRF2 nuclear translocation was not promoted by NaB. Therefore, the present study indicates, for the first time, that NRF2 plays a key role in NaB protection against DN. Other findings suggest that NaB may activate Nrf2 at the transcriptional level, possibly by the inhibition of HDAC activity.
Diarrhea-predominant irritable bowel syndrome (IBS-D) and functional diarrhea (FD) are highly prevalent, and the effectiveness of acupuncture for managing IBS-D and FD is still unknown.The aim of this study was to compare the effectiveness of electroacupuncture with loperamide.It was a prospective, randomized, parallel group controlled trial.A total of 448 participants were randomly assigned to He electroacupuncture group (n = 113), Shu-Mu electroacupuncture group (n = 111), He-Shu-Mu electroacupuncture group (n = 112), or loperamide group (n = 112). Participants in the 3 acupuncture groups received 16 sessions of electroacupuncture during a 4-week treatment phase, whereas participants in the loperamide group received oral loperamide 2 mg thrice daily. The primary outcome was the change from baseline in stool frequency at the end of the 4-weeks treatment. The secondary outcomes were the Bristol scale, the MOS 36-item short form health survey (SF-36), the weekly average number of days with normal defecations and the proportion of adverse events.Stool frequency was significantly reduced at the end of the 4-week treatment in the 4 groups (mean change from baseline, 5.35 times/week). No significant difference was found between the 3 electroacupuncture groups and the loperamide group in the primary outcome (He vs. loperamide group [mean difference 0.6, 95% CI, –1.2 to 2.4]; Shu-Mu vs. loperamide group [0.4, 95% CI, –1.4 to 2.3]; He-Shu-Mu vs. loperamide group [0.0, 95% CI, –1.8 to 1.8]). Both electroacupuncture and loperamide significantly improved the mean score of Bristol scale and increased the weekly average number of days with normal defecations and the mean scores of SF-36; they were equivalent in these outcomes. However, the participants in electroacupuncture groups did not report fewer adverse events than those in the loperamide group. Similar results were found in a subgroup analysis of separating patients with IBS-D and FD patients.Electroacupuncture is equivalent to loperamide for reducing stool frequency in IBS-D and FD patients. Further studies on cost effectiveness of acupuncture are warranted.
An approach to synthesize monodisperse nanospheres with nanoporous structure through a solvent extraction route using an acid-base-coupled extractant has been developed. The nanospheres form through self-assembly and templating by reverse micelles in the organic solvent extraction systems. More importantly, the used extractant in this route can be recycled. The power of this approach is demonstrated by the synthesis of monodisperse iron phosphate nanospheres, exhibiting promising applications in energy storage. The synthetic parameters have been optimized. Based on this, a possible formation mechanism is also proposed. The synthetic procedure is relatively simple and could be extended to synthesize other water-insoluble inorganic metal salts.
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