New Tubulocentric Insights for Diabetic Nephropathy: From Pathophysiology to Treatment

The prevalence of diabetes is increasing worldwide, and one of the most important complications, diabetic nephropathy, constitutes a significant global health care and socioeconomic burden. Glomerular dysfunction is a major factor in the development and progression of diabetic nephropathy. However, emerging evidence suggests that tubular damage also plays an important role in the pathogenesis of diabetic nephropathy. This tubulocentric view shifts the focus markedly from glomeruli to proximal tubules, which might have an important role as a trigger or a driver in the early development and progression of diabetic nephropathy. Accordingly, numerous studies have focused on several different tubular damage markers that are clinically indicated as potential biomarkers for the early detection of diabetic nephropathy. Furthermore, these findings are relevant for identifying therapeutics for diabetic nephropathy that target the proximal tubules. This review outlines new tubulocentric insights into diabetic nephropathy, from pathophysiological mechanisms to diagnostic and therapeutic approaches

The Fingerprint of Climate Change and Urbanization in South Korea

Understanding long-term changes in precipitation and temperature patterns is important in the detection and characterization of climate change, as is understanding the implications of climate change when performing impact assessments. This study uses a statistically robust methodology to quantify long-, medium- and short-term changes for evaluating the degree to which climate change and urbanization have caused temporal changes in precipitation and temperature in South Korea. We sought to identify a fingerprint of changes in precipitation and temperature based on statistically significant differences at multiple-timescales. This study evaluates historical weather data during a 40-year period (1973–2012) and from 54 weather stations. Our results demonstrate that between 1993–2012, minimum and maximum temperature trends in the vicinity of urban and agricultural areas are significantly different from the two previous decades (1973–1992). The results for precipitation amounts show significant differences in urban areas. These results indicate that the climate in urbanized areas has been affected by both the heat island effect and global warming-caused climate change. The increase in the number of rainfall events in agricultural areas is highly significant, although the temporal trends for precipitation amounts showed no significant differences. Overall, the impacts of climate change and urbanization in South Korea have not been continuous over time and have been expressed locally and regionally in terms of precipitation and temperature changes

Signal Transduction Mechanisms Underlying Group I mGluR-mediated Increase in Frequency and Amplitude of Spontaneous EPSCs in the Spinal Trigeminal Subnucleus Oralis of the Rat

Group I mGluRs (mGluR1 and 5) pre- and/or postsynaptically regulate synaptic transmission at glutamatergic synapses. By recording spontaneous EPSCs (sEPSCs) in the spinal trigeminal subnucleus oralis (Vo), we here investigated the regulation of glutamatergic transmission through the activation of group I mGluRs. Bath-applied DHPG (10 μM/5 min), activating the group I mGluRs, increased sEPSCs both in frequency and amplitude; particularly, the increased amplitude was long-lasting. The DHPG-induced increases of sEPSC frequency and amplitude were not NMDA receptor-dependent. The DHPG-induced increase in the frequency of sEPSCs, the presynaptic effect being further confirmed by the DHPG effect on paired-pulse ratio of trigeminal tract-evoked EPSCs, an index of presynaptic modulation, was significantly but partially reduced by blockades of voltage-dependent sodium channel, mGluR1 or mGluR5. Interestingly, PKC inhibition markedly enhanced the DHPG-induced increase of sEPSC frequency, which was mainly accomplished through mGluR1, indicating an inhibitory role of PKC. In contrast, the DHPG-induced increase of sEPSC amplitude was not affected by mGluR1 or mGluR5 antagonists although the long-lasting property of the increase was disappeared; however, the increase was completely inhibited by blocking both mGluR1 and mGluR5. Further study of signal transduction mechanisms revealed that PLC and CaMKII mediated the increases of sEPSC in both frequency and amplitude by DHPG, while IP3 receptor, NO and ERK only that of amplitude during DHPG application. Altogether, these results indicate that the activation of group I mGluRs and their signal transduction pathways differentially regulate glutamate release and synaptic responses in Vo, thereby contributing to the processing of somatosensory signals from orofacial region

Potassium chloride elicits enhancement of bilobalide and Ginkgolides production by Ginkgo biloba cell cultures

This study investigated the ability of potassium chloride (KCl) to elicit the production of bilobalide (BB), ginkgolide A (GA) and ginkgolide B (GB) by Ginkgo biloba cell suspension cultures. The salt stress by KCl treatments increased production of BB, GA and GB in both suspended cells and cultured medium. Especially, treatment of KCl 800 mM of highest concentration was stimulated emission into cultured medium BB, GA and GB compounds accumulated in cells. Although KCl 800 mM severely inhibited cells growth, the maximum content of GA and GB in cells was obtained in the treatment of KCl 800 mM, which was 1.9 and 4.0 times higher than the control. These results thus suggest that salt stress can afford enhanced production of secondary metabolites by plant cell cultures

Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin for efficient tumor-targeted chemotherapy

Since the discovery that nano-scaled particulates can easily be incorporated into tumors via the enhanced permeability and retention (EPR) effect, such nanostructures have been exploited as therapeutic small molecule delivery systems. However, the convoluted synthetic process of conventional nanostructures has impeded their feasibility and reproducibility in clinical applications. Herein, we report an easily prepared formulation of self-assembled nanostructures for systemic delivery of the anti-cancer drug doxorubicin (DOX). Phenylboronic acid (PBA) was grafted onto the polymeric backbone of poly(maleic anhydride). pPBA-DOX nanocomplexes were prepared by simple mixing, on the basis of the strong interaction between the 1,3-diol of DOX and the PBA moiety on pPBA. Three nanocomplexes (1, 2, 4) were designed on the basis of [PBA]:[DOX] molar ratios of 1: 1, 2: 1, and 4: 1, respectively, to investigate the function of the residual PBA moiety as a targeting ligand. An acid-labile drug release profile was observed, owing to the intrinsic properties of the phenylboronic ester. Moreover, the tumor-targeting ability of the nanocomplexes was demonstrated, both in vitro by confocal microscopy and in vivo by fluorescence imaging, to be driven by an inherent property of the residual PBA. Ligand competition assays with free PBA pre-treatment demonstrated the targeting effect of the residual PBA from the nanocomplexes 2 and 4. Finally, the nanocomplexes 2 and 4, compared with the free DOX, exhibited significantly greater anti-cancer effects in vitro and even in vivo. Our pPBA-DOX nanocomplex enables a new paradigm for self-assembled nanostructures with potential biomedical applications.115Ysciescopu