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Objective: To investigate the effects of poly(ADP-ribose) polymerase-1 (PARP-1) on angiotensin II (Ang II)-induced plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) in rat mesangial cells (RMCs). Methods: Followed by serum starvation for 16 h, RMCs were exposed to Ang II for an indicated time to examine the protein expression of PARP-1. The cells were treated with or without Ang II for 12-24 h in the presence or absence of an inhibitor of PARP, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride (PJ34) or small interfering RNA (siRNA) duplexes targeting PARP-1. The mRNA and protein expressions of PARP-1, PAI-1 and FN were determined by real-time RT-PCR and Western blot, respectively. The activity of PARP-1 was examined by colorimetric assay. Results: Ang II did not only significantly induce PARP-1 expression and activity, but also increased PAI-1 and FN expression in RMCs. All these responses induced by Ang II were significantly inhibited by both the PARP inhibitor PJ34 and downregulating PARP-1 with the siRNA technique. Conclusions: Our data suggest that PARP-1 mediates Ang II-induced PAI-1 and FN in RMCs and may thus represent a potential therapeutic target in the treatment of glomerular disease. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Transforming growth factor-β1 (TGF-β1) promotes tissue fibrosis by upregulating genes encoding extracellular matrix proteins and by increasing the synthesis of plasminogen activator inhibitor-1 (PAI-1). TGF-β1 induces cellular reactive oxygen species (ROS) and PAI-1 promoter region has binding sites for redox sensitive transcription factors. We, therefore, hypothesized that TGF-β1-induced upregulation of PAI-1 is ROS-dependent. Using cultured glomerular mesangial cells, we confirmed that TGF-β1 induces cellular ROS, upregulates PAI-1 mRNA and protein expression, and suppresses plasmin activity. We further demonstrated that H2O2 stimulates PAI-1 expression and suppresses plasmin activity and that N-acetylcysteine effectively reverses TGF-β1- and H2O2-induced changes in PAI-1 expression and plasmin activity. Basal as well as TGF-β1- and H2O2-induced PAI-1 expression was upregulated by depletion of intracellular GSH. The present data demonstrate that TGF-β1-induced PAI-1 in mesangial cells is ROS-dependent and imply that cellular ROS may be potential therapeutic targets in glomerular fibrosis. [Copyright &y& Elsevier]

Oceanic submesoscale flows are considered to be a crucial conduit for the downscale transfer of oceanic mesoscale kinetic energy and upper-ocean material exchange, both laterally and vertically, but defining observations revealing submesoscale dynamics and/or transport properties remain sparse. Here, we report on an elaborate observation of a warm and fresh filament intruding into a cyclonic mesoscale eddy. By integrating cruise measurements, satellite observations, particle-tracking simulations, and the trajectory of a surface drifter, we show that the filament originated from an anticyclonic eddy immediately to the west of the cyclonic eddy, and the evolution of the filament was mainly due to the geostrophic flows associated with the eddy pair. Our observations reveal the mass exchange of the eddy pair and suggest that submesoscale flows can degrade the coherence of mesoscale eddies, providing important implications for the transport properties of mesoscale eddies. Vigorous submesoscale turbulence was found within the eddy core region, due to filamentous intrusion and frontogenesis. Our findings have thus offered novel insights into the dynamics and transport properties of oceanic submesoscale flows, which should be taken into account in their simulation and parameterization in ocean and climate models. Significance Statement: Mesoscale eddies, with a spatial scale from tens to hundreds of kilometers, are ubiquitous in the global ocean. Carrying the largest proportion of oceanic kinetic energy, mesoscale eddies play a key role in ocean dynamics and have important applications for marine biology. Although mesoscale eddies have been studied extensively over the past decades, there are two major issues that remain inconclusive: (i) How do mesoscale eddies dissipate? (ii) Can eddies coherently trap waters when moving over a long distance? Recent studies, mostly through computer simulations, suggest that oceanic submesoscale processes, with a typical scale of a few kilometers, are highly relevant to the above two issues. This study presents a rare observation of a filament intruding into a cyclonic eddy. Because of this filament intrusion, submesoscale activities are enhanced near the eddy core area, in contrast to previous observations that normally suggest weaker submesoscale activities in the eddy core area than at eddy peripheries. Such dedicated process-oriented observations provide unique opportunities for better understanding the dynamics and transport properties of mesoscale eddies and submesoscale processes. [ABSTRACT FROM AUTHOR]

Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future. [ABSTRACT FROM AUTHOR]

Background/Aims: Since renal fibrosis always predisposes end-stage renal disease, elucidation of the molecular mechanisms that underlie the progression of renal fibrosis may substantially improve the understanding and treatment for renal failure. Previous studies have highlighted an important counteraction between transforming growth factor β 1 (TGFβ1) and bone morphogenic protein 7 (BMP7) in the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells during chronic renal injury. Macrophages are also believed to play a critical role in renal fibrosis. However, the relationship between macrophages and EMT is unknown. Methods: Here, we used a mouse unilateral ureteral obstruction (UUO) model to address to these questions, and analyzed macrophage and its subpopulations purified by flow cytometry. Results: We found that the recruited macrophages are polarized to a M2 subtype after renal injury. M2 macrophages released high levels TGFβ1 to suppress BMP7 to enhance EMT-induced renal fibrosis. Depletion of M2 macrophages, but not of M1 macrophages, specifically inhibited EMT, and subsequently the renal fibrosis. Adoptive transplantation of M2 macrophages deteriorated renal fibrosis. Conclusion: Thus, our study highlights M2 macrophages as a critical target for treating renal fibrosis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The capacity of CO2 uptake in the Chukchi Sea is particularly sensitive to rapid physical and biological changes. However, scarce field observations pose a challenge in understanding the long‐term trend of CO2 uptake capacity on this continental shelf. We adopted a machine‐learning‐based approach to construct a 17‐years (2003–2019) long‐term time series of summer sea surface partial pressure of CO2 (pCO2) from remote sensing products. We show that the long‐term increase in CO2 uptake capacity can be attributed to strong and enhanced biological uptake. In addition, the intraseasonal variability of surface pCO2 in early summer confirms the crucial role of sea ice melt and the subsequently enhanced photosynthesis as soon as the surface ocean converts into an open system. Our results thus highlight the use of remote sensing data in interpolating/extrapolating the highly dynamic carbonate system in the continental shelf sea and shed light into future studies involving machine learning or algorithms. Plain Language Summary: The climate change in the recent decades has caused remarkable sea surface warming in the Arctic Ocean, with its warming rate twice higher than the global average. The Arctic warming could have some consequences such as shrinkage of sea ice and increase of freshwater storage which profoundly affect the carbon cycle in the Arctic Ocean. The Chukchi Sea serves as the largest oceanic CO2 sink in the Arctic Ocean, yet its long‐term variation and associated mechanism remain unclear due to undersampling. In this study, we adopted a machine‐learning‐based model to construct a 17‐years long‐term time series of sea surface partial pressure of CO2 (pCO2) from satellite observations. Results showed that the CO2 uptake capacity in the Chukchi Sea has increased in the recent decades, primarily owing to the increased primary productivity. This study demonstrated the great potential of ocean color remote sensing in retrieving key biogeochemical parameters in polar regions, and providing a powerful tool for monitoring carbonate system for the oceanographic community. Key Points: A machine learning approach was calibrated and validated to obtain sea surface pCO2 from satellite observations in the Chukchi SeaIncrease in CO2 uptake capacity is revealed by a 17‐years (2003–2019) long‐term time series of summer pCO2Strong and enhanced biological uptake contribute to the increase in CO2 uptake capacity [ABSTRACT FROM AUTHOR]

Artificial upwelling, as a geoengineering tool, has received worldwide attention because it may actualize ocean fertilization in a sustainable way, which could potentially alleviate the pressures on the fish stocks and human-driven climate change in the ocean. We reviewed the current knowledge on the development of an artificial upwelling system and its potential environmental effects. Special attention was given to the research progress on the air-lift concept artificial upwelling by Zhejiang University. The research on artificial upwelling over the past few decades has generated a range of devices that have been successfully applied in the field for months. Based on field experiments and the associated modeling results, part of them reported positive effects on increasing primary production and enhancing CO sequestration. However, as a significant disturbance to the environment, especially for large-scale applications, the uncertainties related to the potential effects on ecosystem remain unsolved. Zhejiang University has overcome the technical challenges in designing and fabricating a robust and high efficiency artificial upwelling device which has been examined in two field experiments in Qiandao Lake and one sea trial in the East China Sea. It was investigated that cold and hypoxic deep ocean water (DOW) could be uplifted to the euphotic layer, which could potentially change the nutrient distribution and adjust the N/P ratio. Both simulation and field experiments results confirmed that utilizing self-powered energy to inject compressed air to uplift DOW was a valid and efficient method. Therefore, further field-based research on artificial upwelling, especially for long-term field research is required to test the scientific hypothesis. [ABSTRACT FROM AUTHOR]

Serum fetuin A has been shown to be associated with the risk of vascular calcification and atherosclerosis, and it can predict the onset of cardiovascular mortality in dialysis patients. The carotid intima-media thickness (cIMT) is an accessible and reliable method to identify the subclinical atherosclerosis. The aim of this study was to investigate the relationships between dialysate calcium concentrations and fetuin A or cIMT in patients undergoing peritoneal dialysis (PD). Forty patients, newly diagnosed end-stage renal disease (ESRD) and undergoing peritoneal dialysis, were enrolled in the study, with a calcium content of the peritoneal dialysis (PD) solution of 1.25 mmol/L in 20 patients (low-Ca group) and 1.75 mmol/L in 20 patients (standard-Ca group). The patients were followed up for 12 months after the PD conducted. Serum fetuin A was determined using a human fetuin A enzyme-linked immunosorbent assay kit and cIMT was detected using ultrasonic wave. We observed no difference between two groups with regard to the baseline data of fetuin A, cIMT, calcium, phosphorus, calcium-phosphorus product, high sensitivity CRP (hsCRP), parathyroid hormone (PTH), or lipid parameters. After 12 months follow-up, fetuin A (263.92 ± 16.1 vs. 282.76 ± 21.0, p = 0.017) and calcium-phosphorus product (39.85 ± 7.76 vs. 47.50 ± 6.65, p = 0.009) were obviously lower in the low-Ca group than standard-Ca group, the other serum parameters were not different between these two groups. Compared with baseline data, serum fetuin A concentration significantly reduced in low-Ca group ( p < 0.05). The number of patients with increased cIMT and newly occurring cardiovascular events in the low-Ca group were significantly reduced than standard-Ca group ( p < 0.05). In conclusion, our data suggest that low calcium dialysate treatment is associated with the decreased serum fetuin A concentration and serum calcium-phosphorus product, and it is associated with the reduced number of PD patients with increased cIMT or with newly occurring cardiovascular events. However, more studies with lager sample size should be performed in the future. [ABSTRACT FROM AUTHOR]

PD-L1 (programmed death-ligand 1) is the ligand of PD-1 (programmed cell death protein 1) and regulates inhibitory immune responses. It is well known that PD-L1 suppresses T cell function via binding to PD-1. However, little is known about the role of the PD-1/PD-L1 axis in macrophage polarization. According to previous studies, the function of the PD-1/PD-L1 axis in macrophage polarization is controversial, and the underlying mechanism has not been fully elucidated. Thus, we treated THP-1-derived macrophages with human PD-L1 Fc to determine the role of the PD-1/PD-L1 axis in macrophage polarization. To further explore the mechanism, we performed RNA sequencing and used specific inhibitors to identify the implicated signalling pathways. In this study, we found that PD-L1 induces the upregulation of CD206 expression, which is inhibited by nivolumab, LY294002, U0126, and rapamycin. Evaluation of differentially expressed genes (DEGs) and bioinformatics analysis indicated that PD-L1 also induces the upregulation of the expression of genes that maintain mitochondrial function and mediate metabolic switching. In addition, we did not detect PD-L1-induced CD86 alterations, indicating that PD-L1 treatment has no significant influence on M1 polarization. Taken together, these results suggest that PD-L1 binds to PD-1 and promotes M2 polarization accompanied by mitochondrial function enhancement and metabolic reprogramming via Erk/Akt/mTOR. This study elucidates the role of PD-L1 in macrophage polarization and verifies the underlying mechanisms for the first time. Considering that aberrantly upregulated PD-L1 expression contributes to a wide variety of diseases, targeting PD-L1-mediated macrophage polarization is a prospective therapeutic strategy for both neoplastic and nonneoplastic diseases. • PD-L1 treatment upregulates CD206 but not CD86 expression. • PD-L1-induced DEGs are related to the immune response, mitochondrial function, and metabolism. • Nivolumab, LY294002, U0126, and rapamycin inhibit the PD-L1-stimulated CD206 expression. • PD-L1 promotes M2 polarization via Erk/Akt/mTOR. [ABSTRACT FROM AUTHOR]