Spectroscopic and in silico study of binding mechanism of cynidine‐3‐O‐glucoside with human serum albumin and glycated human serum albumin

The drug–serum albumin interaction plays a dominant role in drug efficacy and disposition. The glycation of serum albumin that occurs during diabetes may affect its drug‐binding properties in vivo. In order to evaluate the interactivity characteristics of cyanidin‐3‐O‐glucoside (C3G) with human serum albumin (HSA) and glycated human serum albumin (gHSA), this study was undertaken using multiple spectroscopic techniques and molecular modeling analysis. Time‐resolved fluorescence and the thermodynamic parameters indicated that the quenching mechanism was static quenching, and hydrogen bonding and Van der Waals force were the main forces. The protein fluorescence could be quenched by C3G, whereas the polarity of the fluorophore was not obviously changed. C3G significantly altered the secondary structure of the proteins. Furthermore, the interaction force that existed in the HSA–C3G system was greater than that in the gHSA–C3G system. Fluorescence excitation emission matrix spectra, red edge excitation shift, Fourier transform infrared spectroscopy and circular dichroism spectra provided further evidence that glycation could inhibit the binding between C3G and proteins. In addition, molecular modeling analysis supported the experimental results. The results provided more details for the application of C3G in the treatment of diabetes.     

Ecology of seed germination of eight non-pioneer tree species from a tropical seasonal rain forest in southwest China

We compared various aspects of the seed biology of eight non-pioneer tree species from a tropical seasonal rain forest in Xishuangbanna, SW China, that differ in time of dispersal, size and fresh seed moisture content (MC). Seeds were tested for germination under laboratory conditions after dehydration to different moisture levels and under 3.5, 10 and 30% solar irradiances in neutral-shade houses. For six species, germination was also compared in forest understory (3.5% light) and center of a forest gap (32.5% light). Under continuous dehydration over activated silica gel, 100% of seeds of four species had lost the ability to germinate after 48 h, and those of all species except Castanopsis hystrix (decreased from >90 to 30% germination) had lost the ability to germinate after 120 h. Four species did not differ in final germination percentages at the three irradiances (i.e. uniform germination). However, final germination percentages of Horsfieldia pandurifolia and Litsea pierrei var. szemaois were significantly lower in 30% than in 10 or 3.5% light, and seeds of Antiaris toxicaria and C. hystrix germinated to higher percentages in 30 and 10% than in 3.5% light. Mean time to germination (MTG) of the eight species (forest and shade house data combined) ranged from 5–5 days for Pometia tomentosa to 72–207days for L. pierrei; MTG for four species was ≤21 days. There was no obvious relationship between relative desiccation resistance and either time of dispersal, MTG or uniformity of germination at the three light levels, or between seed size and MC or MTG. However, the relationship between seed MC at maturity (25–60% fresh mass basis) and MC at 50% loss of seed viability (12.4–42.5%) was significant. Seven of the species fit Garwood’s (Ecol Monogr 53:159–181, 1983) rapid-rainy germination syndrome and one, L. pierrei, either her delayed-rainy or intermediate-dry germination syndrome. However, fresh, non-dehydrated seeds of all eight species germinated in ≤30 days at constant 30°C in light.     

A new gene coding for <Emphasis Type="Italic">p</Emphasis>-coumarate 3-hydroxylase from <Emphasis Type="Italic">Ginkgo biloba</Emphasis>

p-Coumarate 3-hydroxylase (C3H) is a rate-limiting enzyme involved in monolignol biosynthesis. The full-length cDNA from Ginkgo biloba and genomic DNA sequence encoding C3H (designated as GbC3H) were cloned and characterized for the first time by rapid amplification of cDNA ends technique. The full-length cDNA of GbC3H was of 1860 bp containing a 1527 bp open reading frame encoding a cytochrome P450 protein of 508 amino acids with a calculated mol wt of 57.46 kD and an isoelectric point of 7.09. Two introns were present in the GbC3H gene. Comparative and bioinformatic analyses revealed that GbC3H had close similarity with C3Hs from other species and contained a conserved cytochrome P450 cysteine heme-iron ligand signature. Phylogenetic analysis indicated that GbC3H shared a common evolutionary origin based on sequence and had the closest relationship to C3H from gymnosperm species. Southern blot analysis indicated that GbC3H belonged to a small-gene family. Tissue expression pattern analysis revealed the highest expression of GbC3H in roots followed by leaves, and no expression was detected in stems. Only a few proteins of this class have been found, so the cloning and characterization of GbC3H will be useful in understanding the role of C3Hs in the lignin biosynthesis at the molecular level. This text was submitted by the authors in English.     

利用大孔微载体体外制备工程化组织

组织工程从诞生至今已有二十年的历史.微载体在组织工程领域的应用研究近年来才日趋升温.利用大孔微载体Cytopore体外构建工程化微构组织.并基于其聚团特性,进行灌注再装配大组织的尝试.结果20 d内微构组织达最高细胞密度16.4×107 cells/cm3;32 d后.所形成的微构组织整体均质性好、活性高、基质生成丰富;培养后期微构组织发生明显聚团,经灌注再装配得到细胞和基质分布均匀的厘米级(12 mm×6 mm)大组织.说明利用大孔微载体构建工程化组织是一种行之有效、富有潜力的体外组织构建方案,有望构建尺寸>5 mm、细胞和基质分布均匀的大组织.为体外组织构建提供新的思路.     

MDM2 is implicated in high‐glucose‐induced podocyte mitotic catastrophe via Notch1 signalling

Podocyte injury and depletion are essential events involved in the pathogenesis of diabetic nephropathy (DN). As a terminally differentiated cell, podocyte is restricted in ‘post‐mitosis’ state and unable to regenerate. Re‐entering mitotic phase will cause podocyte disastrous death which is defined as mitotic catastrophe (MC). Murine double minute 2 (MDM2), a cell cycle regulator, is widely expressed in renal resident cells including podocytes. Here, we explore whether MDM2 is involved in podocyte MC during hyperglycaemia. We found aberrant mitotic podocytes with multi‐nucleation in DN patients. In vitro, cultured podocytes treated by high glucose (HG) also showed an up‐regulation of mitotic markers and abnormal mitotic status, accompanied by elevated expression of MDM2. HG exposure forced podocytes to enter into S phase and bypass G2/M checkpoint with enhanced expression of Ki67, cyclin B1, Aurora B and p‐H3. Genetic deletion of MDM2 partly reversed HG‐induced mitotic phase re‐entering of podocytes. Moreover, HG‐induced podocyte injury was alleviated by MDM2 knocking down but not by nutlin‐3a, an inhibitor of MDM2‐p53 interaction. Interestingly, knocking down MDM2 or MDM2 overexpression showed inhibition or activation of Notch1 signalling, respectively. In addition, genetic silencing of Notch1 prevented HG‐mediated podocyte MC. In conclusion, high glucose up‐regulates MDM2 expression and leads to podocyte MC. Notch1 signalling is an essential downstream pathway of MDM2 in mediating HG‐induced MC in podocytes.     

Quantify patient-specific coronary material property and its impact on stress/strain calculations using in vivo IVUS data and 3D FSI models: a pilot study

Biomechanics and Modeling in Mechanobiology - Computational models have been used to calculate plaque stress and strain for plaque progression and rupture investigations. An intravascular...