JLP/Foxk1/N-cadherin axis fosters a partial epithelial-mesenchymal transition state in epithelial tubular cells.

Renal tubular epithelial cells (TECs) undergoing partial epithelial-mesenchymal transition (pEMT) during renal fibrosis has been recognized as a featuring and detrimental event. However, the mechanism for redirecting the cell fate of pEMT remains unclear. Here we mapped the temporal expression trajectories of a series of EMT-related molecules in renal fibrosis. It revealed a unique expression profile of N-cadherin of initial rising and late dropdown, which is distinct from that of other mesenchymal markers. The transcription factor Foxk1, which serves as a negative regulator of the N-cadherin gene, was induced by TGF-ß1 but was tightly regulated in the presence of JNK-associated leucine zipper protein (JLP). The loss of JLP resulted in Foxk1 induction, leading to N-cadherin downregulation and compromised cell viability. We propose a novel axis consisting of JLP/Foxk1/N-cadherin in shaping the EMT program and suggest JLP as the checkpoint of the EMT continuum during renal fibrosis progression.

Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker.

The kidney is a mitochondria-rich organ, and kidney diseases are recognized as mitochondria-related pathologies. Intact mitochondrial DNA (mtDNA) maintains normal mitochondrial function. Mitochondrial dysfunction caused by mtDNA damage, including impaired mtDNA replication, mtDNA mutation, mtDNA leakage, and mtDNA methylation, is involved in the progression of kidney diseases. Herein, we review the roles of mtDNA damage in different setting of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). In a variety of kidney diseases, mtDNA damage is closely associated with loss of kidney function. The level of mtDNA in peripheral serum and urine also reflects the status of kidney injury. Alleviating mtDNA damage can promote the recovery of mitochondrial function by exogenous drug treatment and thus reduce kidney injury. In short, we conclude that mtDNA damage may serve as a novel biomarker for assessing kidney injury in different causes of renal dysfunction, which provides a new theoretical basis for mtDNA-targeted intervention as a therapeutic option for kidney diseases.

Spectral effect of streetlamps on urban trees: A simulated study on tissue water, nitrogen, and carbohydrate contents in maple and oak.

Streetlamps enforce night lighting on urban forest trees, but scarce information is available concerning the ecophysiological performance of street trees under these conditions. In this study, maple (Acer truncatum Bunge) and oak (Quercus mongolica Fisch. ex Ledeb.) seedlings were cultured with simulated exposure to streetlamp spectra in white (red/green/blue, 7.7:1.0:2.2) and red plus blue (RB; red/green/blue, 4.6:0.0:1.0) lights with photosynthetic photon flux rate of 80 µmol m-2 s-1 in a 18-h photoperiod. Nitrogen (N) was loaded through 15 weekly applications to an amount of 80 mg N plant-1 to mimic the mineral N deposition to landscape trees. Variables of biomass, carbohydrate accumulation, N and water contents were rarely found difference between the two LED-spectra treatments for both species. Compared to the un-lighted control, the RB spectrum lowered N concentration in oak seedlings and water content in maple seedlings. The white light spectrum resulted in an increase of starch concentration. Carbohydrate concentration had a positive relationship with biomass and N content across two species but a negative relationship with water content in maple seedlings. Overall, streetlamp-lights imposed effects on tree growth by a prolonged photoperiod instead of specific spectrum. Maple had a strong response of water uptake to streetlamp lighting at the cost of carbohydrate consumption, but oak had scarce demand of water-use for growth.

Isolation and characterization of PoWRKY, an abiotic stress-related WRKY transcription factor from Polygonatum odoratum.

WRKY transcription factors play vital roles in response to biotic and abiotic stresses in plants. As a kind of high value medicinal plant, Polygonatum odoratum has an ability to tolerate various abiotic stresses because of the special growth condition. In current study, a novel WRKY gene from P. odoratum is isolated and compared with homologous sequences from other plants. PoWRKY1 possesses two typical WRKY domains and two C2H2 zinc-finger motifs. Evolutionary analysis indicated that PoWRKY1 is most closely related to WRKY protein from Asparagus officinalis. Expression analysis showed that expression of PoWRKY1 is induced by cold and drought stresses but not salt stress. Overexpression of PoWRKY1 in Arabidopsis improved seed germination and root growth of transgenic plants during cold stress and drought. In addition, super oxide dismutase activity and proline content in transgenic plants increased under cold and drought stresses, whereas malondialdehyde levels and relative electrolyte leakage reduced under similar stress conditions. Taken together, these results showed that PoWRKY1 enhances the tolerance to cold and drought stresses. This study lays a potential foundation to understand the molecular mechanism of tolerance to abiotic stress in P. odoratum.

Urinary mitochondrial DNA level as a biomarker of tissue injury in non-diabetic chronic kidney diseases.

BACKGROUND: Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD. METHODS: We recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3 ± 31.8 months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]). RESULTS: The median urinary mtDNA level was 1519.42 (inter-quartile range 511.81-3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r = 0.429, p < 0.001), proteinuria (r = 0.368, p < 0.001), severity of glomerulosclerosis (r = - 0.537, p < 0.001), and tubulointerstitial fibrosis (r = - 0.374, p = 0.014). The overall rate of eGFR decline was - 2.18 ± 5.94 ml/min/1.73m2 per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors. CONCLUSION: Urinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.

Anti-inflammatory effects of vinpocetine on the functional expression of nuclear factor-kappa B and tumor necrosis factor-alpha in a rat model of cerebral ischemia-reperfusion injury.

OBJECTIVE: The restoration of blood flow to the brain after ischemic stroke prevents further, extensive damage but can result in reperfusion injury. The inflammation response is one of many factors involved in cerebral ischemia-reperfusion injury. This study investigated the use of vinpocetine, a drug used to treat cognitive impairment, to explore its effects on inflammation in a rat model of cerebral ischemia-reperfusion. METHODS: Wistar rats were randomly assigned to a control group, (n=40) a cerebral ischemia-reperfusion group (n=52) and a vinpocetine cerebral ischemia-reperfusion group (n=52). A model of middle cerebral artery occlusion was induced for 2h followed by reperfusion and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining 6h, 24h, 3 days, and 7 days after reperfusion. The dry-wet weight method was used to measure brain water content and evaluate the extent of brain edema. Immunohistochemistry and in-situ hybridization were used to detect the expression of NF-κB and TNF-α. RESULTS: The NF-κB levels in ischemic brain tissue increased 6h after reperfusion and the TNF-α levels increased at 24h, both reached their peaks at day 3 then decreased gradually, but remained above the controls at day 7. Vinpocetine decreased the levels of NF-κB and TNF-α 24h and 3 days after reperfusion. CONCLUSION: NF-κB and TNF-α is associated with changes in brain edema and infarct volume. Vinpocetine decreases the expression of NF-κB and TNF-α and inhibits the inflammatory response after cerebral ischemia-reperfusion.