高敏C-反应蛋白在紫癜性肾炎患儿中的应用

目的：探讨血清高敏C-反应蛋白（hs-CRP）在儿童紫癜性肾炎（HSPN）临床分型与病理分级中的应用价值,为基层医院提供一个可评价HSPN患儿病情严重程度的实验室相关指标。方法：应用免疫比浊法检测210例HSPN患儿不同临床分型与病理分级中的血清hs-CRP的水平,并与住院的70例的正常儿童作对照组进行比较。采用Pearson秩相关分析得出HSPN患儿血清hs-CRP水平临床分型与及病理分级的关系。结果：HSPN患儿血清hs-CRP水平明显高于对照组（HSPN组6.4±3.5 mg/L,对照组0.7±0.1mg/L）,差异有统计学意义（t=1.021,P=0.003）。HSPN患儿的血清hs-CRP水平与其临床分型的严重程度存在正相关（r=0.913,P〈0.05）。而HSPN患儿血清hs-CRP水平与其病理分级的关系也呈正相关（r=0.901,P〈0.05）。结论：随着HSPN患儿临床分型与病理分级的增高,其血清hs-CRP水平显著升高,HSPN患儿血清hs-CRP水平与其临床分型和病理分级之间均呈显著正相关,检测HSPN患儿血清hs-CRP水平可预测其临床分型和病理分级的程度,即HSPN患儿血清hs-CRP水平越高提示其临床分型和病理分级越重,因此检测HSPN患儿血清hs-CRP水平有助于评估HSPN患儿的病情、治疗效果和预后情况。     

The stacked over-expression of FPS, CYP71AV1 and CPR genes leads to the increase of artemisinin level in Artemisia annua L.

Artemisinin is an endoperoxide sesquiterpene lactone isolated from the aerial parts of Artemisia annua L., and is presently the most potent anti-malarial drug. Owing to the low yield of artemisinin from A. annua as well as the widespread application of artemisinin-based combination therapy recommended by the World Health Organization, the global demand for artemisinin is substantially increasing and is therefore rendering artemisinin in short supply. An economical way to increase artemisinin production is to increase the content of artemisinin in A. annua. In this study, three key genes in the artemisinin biosynthesis pathway, encoding farnesyl diphosphate synthase, amorpha-4, 11-diene C-12 oxidase and its redox partner cytochrome P450 reductase, were over-expressed in A. annua through Agrobacterium-mediated transformation. The transgenic lines were confirmed by Southern blotting and the over-expressions of the genes were demonstrated by real-time PCR assays. The HPLC analysis showed that the artemisinin contents in transgenic lines were increased significantly, with the highest one found to be 3.6-fold higher (2.9 mg/g FW) than that of the control. These results demonstrate that multigene engineering is an effective way to enhance artemisinin content in A. annua.     

Effects of sand burial depth on the root system of Salix cheilophila seedlings in Mu Us Sandy Land, Inner Mongolia, China

Salix cheilophila Schneid. is a naturally occurring Salix species in Mu Us Sandy Land, Inner Mongolia, China. We focused on the morphological adaptability of S. cheilophila to sand dune burial. For morphological measurements, 32 S. cheilophila seedlings were removed from a community which was in the process of being buried by a shifting sand dune. Each seedling collected included the entire root system. We measured the number, length, and biomass of the adventitious roots, primary lateral roots, and taproot, and compared the morphological characteristics of the root system, including adventitious roots, for seedlings buried to various levels in the sand. The growth range of adventitious roots increased as the length of the buried portion of the main shoot increased. In addition, the total dry weight of all current-year shoots tended to increase gradually with increasing total dry weight of the adventitious roots. These results suggest that S. cheilophila tends to make use of the sedimentary sand layer that accompanies shifting sand dunes. However, there was no correlation between biomass or number of adventitious roots and the length of the buried part of the main shoot. Thus, S. cheilophila does not grow adventitious roots proportional to the buried part. These morphological characteristics of the root system, including the adventitious roots, may indicate that S. cheilophila has poor morphological adaptability to sand dune burial.     

Brain structure and spatial sensitivity profile assessing by near‐infrared spectroscopy modeling based on 3D MRI data

The goal of this study is to prove that the light propagation in the head by used the 3‐D optical model from in vivo MRI data set can also provide significant characteristics on the spatial sensitivity of cerebral cortex folding geometry based on Monte Carlo simulation. Thus, we proposed a MRI based approach for 3‐D brain modeling of near‐infrared spectroscopy (NIRS). In the results, the spatial sensitivity profile of the cerebral cortex folding geometry and the arrangement of source‐detector separation have being necessarily considered for applications of functional NIRS. The optimal choice of source‐detector separation is suggested within 3–3.5 cm by the received intensity with different source‐detector separations and the ratio of received light from the gray and white matter layer is greater than 50%. Additionally, this study has demonstrated the capability of NIRS in not only assessing the functional but also detecting the structural change of the brain by taking advantage of the low scattering and absorption coefficients observed in CSF of sagittal view. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Determination of the Human Antibody Response to the Neutralization Epitopes Encompassing Amino Acids 313–327 and 432–443 of Hepatitis C Virus E1E2 Glycoproteins

It has been reported that monoclonal antibodies (MAbs) to the E1E2 glycoproteins may have the potential to prevent hepatitis C virus (HCV) infection. The protective epitopes targeted by these MAbs have been mapped to the regionsencompassing amino acids 313–327 and 432–443. In this study, we synthesized these two peptides and tested the reactivity of serum samples from 336 patients, 210 of whichwere from Chronic Hepatitis C (CHC) patients infected with diverse HCV genotypes.The remaining 126 samples were isolated from patients who had spontaneously clearedHCV infection.In the chronic HCV-infected group (CHC group), the prevalence of human serum antibodies reactive to epitopes 313–327 and 432–443was 24.29%(51 of 210) and4.76%(10 of 210),respectively. In thespontaneousclearance group (SC group),the prevalence was 0.79%(1 of 126) and 12.70%(16 of 126), respectively.The positive serum samples that contained antibodies reactive to epitope 313–327 neutralizedHCV pseudoparticles (HCVpp) bearing the envelope glycoproteins of genotypes 1a or 1b and/or 4, but genotypes 2a, 3a, 5 and 6 were not neutralized. The neutralizing activity of these serum samples could not be inhibited by peptide 313–327. Six samples (SC17, SC38, SC86, SC92, CHC75 and CHC198) containing antibodies reactive to epitope 432–443 had cross-genotype neutralizing activities. Theneutralizing activityof SC38, SC86, SC92 and CHC75waspartiallyinhibited by peptide 432–443. However,the neutralizing activity of sample SC17 for genotype 4HCVpp and sample CHC198 for genotype 1b HCVppwere notinhibited by the peptide.This study identifies the neutralizing ability of endogenous anti-HCV antibodies and warrants the exploration of antibodies reactive to epitope432–443as sources for future antibody therapies.     

N-Substituted Benzyl Matrinic Acid Derivatives Inhibit Hepatitis C Virus (HCV) Replication through Down-Regulating Host Heat-Stress Cognate 70 (Hsc70) Expression

Heat-stress cognate 70 (Hsc70) is a host factor that helps hepatitis C virus (HCV) to complete its life cycle in infected hepatocytes. Using Hsc70 as a target for HCV inhibition, a series of novel N-substituted benzyl matrinic/sophoridinic acid derivatives was synthesized and evaluated for their anti-HCV activity in vitro. Among these analogues, compound 7c possessing N-p-methylbenzyl afforded an appealing ability to inhibit HCV replication with SI value over 53. Furthermore, it showed a good oral pharmacokinetic profile with area-under-curve (AUC) of 13.4 µM·h, and a considerably good safety in oral administration in mice (LD₅₀>1000 mg/kg). As 7c suppresses HCV replication via an action mode distinctly different from that of the marketed anti-HCV drugs, it has been selected as a new mechanism anti-HCV candidate for further investigation, with an advantage of no or decreased chance to induce drug-resistant mutations.     

TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator

The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1^−/−) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1^−/− mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1^−/− mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.