ARTICLE | doi:10.20944/preprints201803.0030.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: 1-DNJ; diabetic cardiomyopathy; fibrosis; N-glycosylation; α 1,6-Fucosylation
Online: 5 March 2018 (04:08:49 CET)
The Chinese drug Bombyx Batryticatus mori.L which also named as the white stiff silkworm is widely used in clinics, due to the significant antispasmodic and promotional blood circulation effects. In addition, its hypoglycemic effect is also recognized in recent years. From a pathological point of view, the enzymatic glycosylation and non-enzymatic glycation both have important roles in regulating properties of proteins and are associated with Diabetes. With the db/db mouse model, we examined the alterations of N-glycosylation of diabetic myocardium at primary stage and clarify the differences in glycosylation of myocardium before and after with 1-DNJ treatment. Hydrophilic chromatography solid phase extraction enrichment and LC-MS/MS identification was applied to profile the alternations in protein glycosylation. Meanwhile, N-glycan α1, 6-fucosylation alterations were profiled with LCA lectin blot and FITC-labelled lectin affinity histochemistry. Our results showed that AGES, hydroxyproline, CTGF and other serum indicators and fibrosis related cytokines expressional levels were reduced significantly by 1-DNJ in a dose-dependent manner. In order to verify this result, the well-known pathway of TGF-β/smad2/3 was picked out and α1, 6-core fucosylated TGFR-βⅡwas semi-quantified with western blot method. The result sustained the conclusion from LCA lectin affinity histochemistry and lectin blot analysis. The expressional level of α1, 6-fucosyltransferase mRNA was increased in the myocardium of db/db mice, however, the 1-DNJ administration did not show obvious inhibitory effect on FU8 expression. This unexpected result can be interpreted as 1-DNJ plays the roles by reducing the concentration of substrate rather than inhibiting α1，6-fucose glycosyltransferase expression. Meanwhile, 1-DNJ crude extract from BBm with some flavonoids accompany can also play the roles of anti-oxidant, and all the chemicals protect the diabetic myocardium from hyperglycemia damage commonly.
ARTICLE | doi:10.20944/preprints201804.0350.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: 1-DNJ; diabetic cardiomyopathy; fibrosis; N-glycosylation; α1,6-fucosylation
Online: 27 April 2018 (06:13:25 CEST)
The traditional Chinese drug Bombyx Batryticatus mori.L (BBm) which is also named the white stiff silkworm has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease and clarify the therapeutic effect of 1-DNJ extracted from BBm, we used the db/db mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an LC-MS/MS identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. AGEs, hydroxyproline, CTGF and other serum biochemical indicators were measured with ELISA. In addition, the α1,6-fucosylation of N-glycans was profiled with LCA lectin blots and FITC-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α1,6-fucosylation was significant. To verify this result, the well-known TGF-β/smad2/3 pathway was selected, and core α1,6-fucosylated TGFR-βⅡ was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained from LCA lectin affinity histochemistry and lectin blot analysis. The expression level of FUT8 mRNA was also detected, and the results showed that 1-DNJ administration did not cause obvious inhibitory effects on FUT8 expression. Therefore, the mechanism of 1-DNJ to relieve the DCM-associated fibrosis can be concluded as the inhibition of N-GlcNAc formation and the reduction of substrate concentration.
ARTICLE | doi:10.20944/preprints201608.0083.v1
Subject: Earth Sciences, Environmental Sciences Keywords: deformation; interferometry; geotechnical models; non‐linear problem; synthetic aperture radar (SAR); time‐series
Online: 8 August 2016 (14:50:19 CEST)
This paper is aimed at studying the temporal evolution of the surface displacements occurred over the past few years in the ocean-reclaimed platforms of the Shanghai megacity (China), which are mainly ascribable to consolidation processes of large dredger fills and alluvial deposits. With respect to previous analyses carried out over the same area, this work provides a joint multi-platform differential interferometry synthetic aperture radar (DInSAR) analysis, based on the application of the advanced Small BAseline Subset (SBAS) algorithm. This led us to retrieve long-term deformation time-series that are helpful for a better understanding of the on-going deformation phenomena. To this aim, we have exploited two sequences of SAR data collected by the ASAR/ENVISAT and by the COSMO-SkyMed (CSK) sensors, respectively, spanning the whole time period from 2007 to 2016. Unfortunately, the large time gap (of about three years) existing between the available ASAR/ENVISAT and CSK datasets gave rise to additional difficulties for their combination. Nevertheless, this problem has been faced by benefiting from the knowledge of a time-dependent model describing the temporal evolution of the expected deformations affecting the Shanghai ocean-reclaimed platforms.