Patients with a relapse of idiopathic nephrotic syndrome have significantly increased levels of serum complement component 5a (C5a), and proteinuria has been noted in mice treated with C5a via changes in permeability of kidney endothelial cells (KECs) in established animal models. However, the apoptosis of KECs treated with high concentrations of C5a has also been observed. As mitochondrial damage is known to be important in cell apoptosis, the aim of this study was to examine the association between C5a-induced mouse KEC apoptosis and mitochondrial damage. Mouse KECs were isolated and treated with different concentrations of C5a. Cell viability assays showed that a high-concentration mouse recombinant protein C5a (rmC5a) treatment reduced mouse KEC growth. Cell cycle phase analysis, including apoptosis (sub-G1 phase) showed an increased percentage of the subG1 phase with a high-concentration rmC5a treatment. Cytochrome c and caspase 3/9 activities were significantly induced in the mouse KECs after a high-dose rmC5a (50 ng/mL) treatment, and this was rescued by pretreatment with the C5a receptor (C5aR) inhibitor (W-54011) and N-acetylcysteine (NAC). Reactive oxygen species (ROS) formation was detected in C5a-treated mouse KECs; however, W-54011 or NAC pretreatment inhibited high-dose rmC5a-induced ROS formation and also reduced cytochrome c release, apoptotic cell formation, and apoptotic DNA fragmentation. These factors determined the apoptosis of mouse KECs treated with high-dose C5a through C5aR and subsequently led to apoptosis via ROS regeneration and cytochrome c release. The results showed that high concentrations of C5a induced mouse KEC apoptosis via a C5aR/ROS/mitochondria-dependent pathway. These findings may shed light on the potential mechanism of glomerular sclerosis, a process in idiopathic nephrotic syndrome causing renal function impairment.
Abnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer in men. Recent animal studies on gut microbiome suggested that gut bacteria are involved in sex steroid metabolism; however, the underlying mechanisms and bacterial taxa remain elusive. Denitrifying betaproteobacteria Thauera spp. are metabolically versatile and often distributed in the animal gut. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of catabolizing androgen under both aerobic and anaerobic conditions. We administered C57BL/6 mice (aged 7 weeks) with strain GDN1 through oral gavage. The strain GDN1 administration caused a minor increase in the relative abundance of Thauera (≤0.1%); however, it has profound effects on the host physiology and gut bacterial community. The results of our ELISA assay and metabolite profile analysis indicated an approximately 50% reduction in serum androgen levels in the strain GDN1-administered male mice. Moreover, androgenic ring-cleaved metabolites were detected in the fecal extracts of the strain GDN1-administered mice. Furthermore, our RT – qPCR results revealed the expression of the androgen catabolism genes in the gut of the strain GDN1-administered mice. We found that the administered strain GDN1 regulated mouse serum androgen levels, possibly because it blocked androgen recycling through enterohepatic circulation. This study discovered that sex steroids serve as a carbon source of gut bacteria; moreover, host circulating androgen levels may be regulated by androgen-catabolizing gut bacteria. Our data thus indicate the possible applicability of androgen-catabolic gut bacteria as potent probiotics in alternative therapy of hyperandrogenism.
Poly(butylene succinate) (PBSu) and poly(ethylene adipate) (PEA), isomeric to each other, are mixed in a miscible state, and PBSu crystallized at T c’s where PEA is kept at a molten state. PBSu upon crystallization in the presence of isomeric PEA at various Tc’s develops sector-face spherulitic patterns, which are shown to originate from a common nuclei center. The two faces of sector-face PBSu spherulites are more strikingly contrast when PBSu is highly diluted by isomeric PEA in PBSu/PEA mixtures (PEA = 70–80%) and crystallized at intermediate T c = 50–60 °C. The main characteristics of crystallized PBSu and lamellar assembly mechanisms in these two faces were investigated using POM, SEM, AFM, and DSC. For both faces (ring-banded vs dendritic) of the sector-face PBSu spherulites, the lamellar assembly mechanism differs, but the growth is similar by repeating with periodic multiplication of fractal branches (whose number is proportional to square of radius) in the next cycle; thus, the lamellae fractal branches not only able to interpret the periodic optical banding but also account for filling the expanding spherulite. This growth mechanism is readily accounted by many fractal patterns in the nature.
Due to the popularity of network applications, such as multimedia, online shopping, Internet of Things (IoT), and 5G, the contents cached in the routers are frequently replaced in Content-Centric Networking (CCN). Generally, cache miss causes numerous propagated packets to get the required content that deteriorates network congestion and delay the response time of consumers. Many caching strategies and routing policies were proposed to solve the problem. This paper presents an alternative solution by designing a query-based routing table update mechanism to increase the accuracy of routing tables. By adding an additional query content in interest packets, our approach real-time explores the cached content in routers and updated the routing table accordingly. This paper uses a general network simulator, ndnSIM, to compare basic CCN and our approach. The results show that our approach improves the response time of consumers and network congestion and is compatible with general forwarding strategies.
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