High levels of blood glycemic indicators are associated with chronic kidney disease prevalence in non-diabetic adults: Cross-sectional data from the national health and nutrition examination survey 2005-2016.

Objective: Hyperglycemia in individuals with diabetes is associated with chronic kidney disease (CKD); however, little is known about its association with those without diabetes. Our goal was to investigate the association between glycemic indicators and CKD in individuals without diabetes. Methods: This cross-sectional study included 9610 participants without diabetes who participated in the Health and Nutrition Examination Survey between 2005 and 2016. Exposures included postprandial glucose dip (PGD), fasting blood glucose (FBG), oral glucose tolerance test two-hour blood glucose (OGTT-2HBG), and glycated hemoglobin (HbA1C) levels. Moreover, CKD was defined as an estimated glomerular filtration rate below 60 mL/min per 1.73 m2 or a urinary albumin-creatinine ratio of ≥ 30 mg/g. Two multivariate models were constructed. Interaction effects were also explored. Results: The mean age of the participants was 46.0 years, with 50.3 % being females. The prevalence of CKD was 12.6 %. In the final multivariable models, the odds ratios (ORs) for CKD were 1.51 (95 % confidence interval [CI]: 1.22,1.88, p < 0.001) for participants in the highest quartile of PGD,1.46 (95 %CI: 1.13,1.87, p = 0.004) for OGTT-2HBG, and 1.33 (95 %CI: 1.04,1.70, p = 0.020) for HbA1C, when compared with the quartile 1. No significant association was observed between FBG levels and CKD in the final model. Additionally, interactions were observed between PGD and body mass index, as well as between PGD and alcohol consumption in relation to CKD. Conclusion: The study identified that high levels of PGD, OGTT-2HBG, and HBA1C were significantly associated with a high prevalence of CKD in individuals without diabetes.

Myoloid-related protein 8, an endogenous ligand of Toll-like receptor 4, is involved in epileptogenesis of mesial temporal lobe epilepsy via activation of the nuclear factor-κB pathway in astrocytes.

The role of Toll-like receptor 4 (TLR4) in the activation of innate immunity has been extensively studied in the past several years. Here, we are the first to report that myeloid-related protein 8 (MRP8), an endogenous TLR4 ligand, is involved in the epileptogenesis of mesial temporal lobe epilepsy (MTLE). We find that the expression of MRP8, TLR4, and interleukin 1-ß (IL-1ß) was upregulated in a MTLE model during both acute and chronic disease stages. We next investigated the possible roles played by astrocytes, which have been shown to be the major source of IL-1ß during epilepsy. Stimulation via MRP8 led to the induction of IL-1ß in astrocytes in vitro, accompanied by the activation of Nuclear Factor-κB, while knockdown of TLR4 or inhibition of NF-κB in astrocytes prevented this IL-1ß induction. Thus, MRP8 may potentiate the perpetuation of MTLE by activating the NF-κB pathway in astrocytes, and could be a new target for anticonvulsant therapies.

PKC and RhoA signals cross-talk in Escherichia coli endotoxin induced alterations in brain endothelial permeability.

Escherichia coli endotoxin LPS regulates blood-brain barrier permeability by disrupting the tight junction (TJ) complex between brain endothelial cells. This study used Bend.3 cells to examine the signaling networks involved in the hyperpermeability of the brain endothelial barrier caused by LPS. The LPS-induced alterations in the brain endothelial barrier were associated with PKC (a, ß, ζ) and RhoA, but were independent of PI3K and the tyrosine kinase pathway. Inhibition of PKC (a, ß, ζ) and RhoA activity using shRNA and dominant negative mutants diminished the effects of LPS on the brain's endothelial TJs. The interactions between the PKC and Rho pathways were therefore examined. PKC-a and PKC-ζ, but not PKC-ß interacted with RhoA in Bend.3 cells stimulated by LPS. PKC-a acted as the upstream molecule for Rho and PKC-ζ acted as the downstream target for Rho. Comparing the effect of double inhibition of "Rho and PKC" and single inhibition of "Rho" or "PKC" confirmed that this interaction is critical for LPS-induced brain endothelial cell hyperpermeability. Collectively these data are the first to suggest that LPS affects the brain's endothelial TJ barrier via PKC (a, ß, ζ)- and RhoA, independent of the PI3K and tyrosine kinase pathways. In addition, PKC-a and PKC-ζ, respectively, act as the upstream and downstream regulator for RhoA in the process.

Interleukin-1ß and microRNA-146a in an immature rat model and children with mesial temporal lobe epilepsy.

PURPOSE: Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of mesial temporal lobe epilepsy (MTLE). The aim of this study was to investigate the dynamic expression of interleukin (IL)-1ß as a proinflammatory cytokine and microRNA (miR)-146a as a posttranscriptional inflammation-associated microRNA (miRNA) in the hippocampi of an immature rat model and children with MTLE. METHODS: To study the expression of IL-1ß and miR-146a, we performed a reverse transcription polymerase chain reaction, Western blot, and real-time quantitative PCR on the hippocampi of immature rats at 11 days of age. Expression was monitored in the acute, latent, and chronic stages of disease (2 h and 3 and 8 weeks after induction of lithium-pilocarpine status epilepticus, respectively), and in control hippocampal tissues corresponding to the same timeframes. Similar expression methods were applied to hippocampi obtained from children with MTLE and normal controls. KEY FINDINGS: The expression of IL-1ß and miR-146a in both children and immature rats with MTLE differs according to the stage of MTLE development. Both IL-1ß and miR-146a are significantly up-regulated, but in opposite ways: IL-1ß expression is highest in the acute stage, when expression of miR-146a is at its lowest level; miR-146a expression is highest in the latent stage, when IL-1ß expression is at its lowest level. Both IL-1ß and miR-146a are up-regulated in the chronic stage, but not as much as in the other stages. SIGNIFICANCE: Our study is the first to focus on the expression of miR-146a in the immature rat model of lithium-pilocarpine MTLE and in children with MTLE. We have detected that the expression of proinflammatory cytokine IL-1ß and posttranscriptional inflammation-associated miR-146a is variable depending on the disease stage. Furthermore, both IL-1ß and miR-146a are up-regulated in immature rats and children with MTLE. Our findings elucidate the role of inflammation in the pathogenesis of MTLE in the immature rat model and children. Therefore, modulation of the IL-1ß-miR-146a axis may be a novel therapeutic target in the treatment of MTLE.

The Expression of Interleukin-1b and miRNA-146a in the Cerebral Cortex of Acute Escherichia Coli Meningitis Immature Rat Model.

The main limitation to advances in treatment of bacterial meningitis and its complications is the incomplete knowledge of the pathogenesis and pathophysiology of this disease. The aim of this research is to detect the expression of interleukin (IL)-1ß as pro-inflammatory cytokine and miRNA (miR)-146a as post transcriptional inflammation associated microRNA (miRNA) in the cerebral cortex of acute Escherichia coli (E. coli) meningitis immature rat model. Immature rats in the post natal day 11 (PN11) were used to construct a model of acute E. coli meningitis and served as controls. The expression of IL-1ß and miR-146a were detected in the cerebral cortex by reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative PCR (qPCR) analysis respectively, 24 hours after bacterial inoculation. In the cerebral cortical tissue of acute E. coli meningitis immature rat model the IL-1ß expression was significantly upregulated while the miR-146a expression was significantly downregulated. This study tried to add a new insight on the molecular basis of the E. coli meningitis pathogenesis at its very early stage through detecting the expression of IL-1ß and miR-146a in the cerebral cortex of the infected immature rats. Consequently, modulation of the IL-1ß- miR-146a axis may be a new target for treatment of acute E. coli meningitis.

[Influence of lipopolysaccharide on the permeability of rat brain microvascular endothelial cells and the molecular mechanism].

OBJECTIVE: To study the influence of lipopolysaccharide (LPS) on the permeability of rat brain microvascular endothelial cells (BMECs) and possible molecular mechanism. METHODS: Monolayers of primary rat BMECs were separated and cultured, and then treated with (LPS group) or without LPS (control group). The barrier integrity was measured by transendothelial electrical resistance (TEER) assay. The degrees of RhoA activation were determined by Pull-down assay. The expression levels of p115RhoGEF, zonula occludens-1 (ZO-1), occludin and claudin-5 proteins were detected by Western blot analysis. RESULTS: The average TEER values of rat BMECs in the LPS group were 108.3±4.2 Ω•cm2 and 85.4±2.5 Ω•cm2 respectively 3 and 12 hrs after LPS treatment, which were significantly lower than that in the control group (159.0±8.6 Ω•cm2). Compared with the control group, the activity of RhoA started to increase 5 minutes after LPS treatment, and the expression of p115RhoGEF protein started to increase 1 hr after LPS treatment and the cellular protein levels of ZO-1, occludin and claudin-5 decreased significantly 3 hrs after LPS treatment in the LPS group (P<0.05). CONCLUSIONS: LPS may activate the p115RhoGEF/RhoA pathway and decrease protein expression of ZO-1, occludin and claudin-5, resulting in an increased permeability of rat BMECs.

[Succinic semialdehyde dehydrogenase deficiency].

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder. This paper reports three cases of SSADH deficiency in infants. The infants developed the symptoms including developmental delay, intellectual disability, hypotonia, hyporeflexia and seizures. The electroencephalogram (EEG) showed background slowing and focal spike discharges in all of 3 patients. Head magnetic resonance imaging (MRI) demonstrated abnormalities in 2 patients, including basal ganglia damage and increased T2-weighted signal in bilateral cerebral peduncles. Urinary organic acid analysis with gas chromatography-mass spectrometry (GC-MS) revealed increased levels of 4-hydroxybutyrate (GHB) in 3 patients. SSADH deficiency was definitely diagnosed based on the clinical manifestations and the results of urinary organic acid analysis in the 3 children. It was concluded that early urine organic acid analysis is essential for children presenting with mental retardation, neuropsychiatric disturbance or epilepsy of unknown etiology.