Steroids in the treatment of IgA nephropathy to the improvement of renal survival: a systematic review and meta-analysis

Background

Studies have shown that steroids can improve kidney survival and decrease the risk of proteinuria in patients with Immunoglobulin A nephropathy, but the overall benefit of steroids in the treatment of Immunoglobulin A nephropathy remains controversial. The aim of this study was to evaluate the benefits and risks of steroids for renal survival in adults with Immunoglobulin A nephropathy.

Methodology and Principal Findings

We searched the Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE and EMBASE databases. All eligible studies were measuring at least one of the following outcomes: end-stage renal failure, doubling of serum creatinine and urinary protein excretion. Fifteen relevant trials (n = 1542) that met our inclusion criteria were identified. In a pooled analysis, steroid therapy was associated with statistically significant reduction of the risk in end-stage renal failure (RR: 0.46, 95% CI: 0.27 to 0.79), doubling of serum creatinine (RR = 0.34, 95%CI = 0.15 to 0.77) and reduced urinary protein excretion (MD = −0.47g/day, 95%CI = −0.64 to −0.31).

Conclusions/Significance

We identified that steroid therapy was associated with a decrease of proteinuria and with a statistically significant reduction of the risk in end-stage renal failure. Moreover, subgroup analysis also suggested that long-term steroid therapy had a higher efficiency than standard and short term therapy.     

Genomic characterization and high prevalence of bocaviruses in swine

Using random PCR amplification followed by plasmid subcloning and DNA sequencing, we detected bocavirus related sequences in 9 out of 17 porcine stool samples. Using primer walking, we sequenced the nearly complete genomes of two highly divergent bocaviruses we provisionally named porcine bocavirus 1 isolate H18 (PBoV1-H18) and porcine bocavirus 2 isolate A6 (PBoV2-A6) which differed by 51.8% in their NS1 protein. Phylogenetic analysis indicated that PBoV1-H18 was very closely related to a ～2 Kb central region of a porcine bocavirus-like virus (PBo-LikeV) from Sweden described in 2009. PBoV2-A6 was very closely related to the porcine bocavirus genomes PBoV-1 and PBoV2 from China described in 2010. Among 340 fecal samples collected from different age, asymptomatic swine in five Chinese provinces, the prevalence of PBoV1-H18 and PBoV2-A6 related viruses were 45-75% and 55-70% respectively, with 30-47% of pigs co-infected. PBoV1-A6 related strains were highly conserved, while PBoV2-H18 related strains were more diverse, grouping into two genotypes corresponding to the previously described PBoV1 and PBoV2. Together with the recently described partial bocavirus genomes labeled V6 and V7, a total of three major porcine bocavirus clades have therefore been described to date. Further studies will be required to elucidate the possible pathogenic impact of these diverse bocaviruses either alone or in combination with other porcine viruses.     

Cloning of a novel protein interacting with BRS-3 and its effects in wound repair of bronchial epithelial cells

Bombesin receptor subtype 3 (BRS-3), the orphan bombesin receptor, may play a role in the regulation of stress responses in lung and airway epithelia. Bombesin receptor activated protein (BRAP )is a novel protein we found in our previous study which interacts with BRS-3. This study was designed to observe the subcellular location and wound repair function of BRAP in human bronchial epithelial cells (HBECs). BRAP ORF was amplified by RT-PCR and ligated to pEGFP-C1 vector, and then the recombinant plasmid pEGFP-C1-BRAP was transfected into Hela cells. The location of BRAP protein was observed by laser confocal microscope, and the expression of it was analyzed by Western-blot. At the same time,we built the recombinant plasmid pcDNA3.1(+)-BRAP, transfected it into HBECs and observed its impact on cell cycle and wound repair of HBECs. The results showed that BRAP locates in membrane and cytoplasm and increases significantly in transfected cells. Flow cytometry results demonstrated that the recombinant plasmid increases S phase plus G2 phase of cell cycle by 25%. Microscopic video analysis system showed that the repair index of wounded HBECs increases by 20% through stable expression of BRAP. The present study demonstrated that BRAP locates in the membrane and cytoplasm, suggesting that this protein is a cytoplasm protein, which promotes cell cycle and wound repair of HBECs.     

The first Chinese case of Creutzfeldt-Jakob disease patient with R208H mutation in PRNP

A case of Creutzfeldt-Jakob disease (CJD) with a rare mutation of the prion protein (PrP) gene (PRNP) at codon 208 (R208H), while the codon 129 was a methionine homozygous genotype is reported. The patient initial displayed hand tremor, dizziness and progressive cognitive dysfunction. Subsequently, other symptoms gradually appeared, including cerebellar ataxia and mental disorder. No periodic activity was recorded at electroencephalography (EEG) and 14-3-3 protein in cerebrospinal fluid was negative. Total clinical course was about four months. Retrospective investigation of this family across seven generations did not figure out clear family history. However, genetic analyses revealed six first-degree family members with the R208H allele.Key words: creutzfeldt-Jakob disease, PRNP, R208H     

Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development

The Tet family of enzymes (Tet1/2/3) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Mouse embryonic stem cells (mESCs) highly express Tet1 and have an elevated level of 5hmC. Tet1 has been implicated in ESC maintenance and lineage specification in?vitro but its precise function in development is not well defined. To establish the role of Tet1 in pluripotency and development, we have generated Tet1 mutant mESCs and mice. Tet1(-/-) ESCs have reduced levels of 5hmC and subtle changes in global gene expression, and are pluripotent and support development of live-born mice in tetraploid complementation assay, but display skewed differentiation toward trophectoderm in?vitro. Tet1 mutant mice are viable, fertile, and grossly normal, though some mutant mice have a slightly smaller body size at birth. Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development.     

Infection of H69AR cells with retroviral particles harboring interfering RNAi significantly reduced the multidrug resistance of these small cell lung cancer cells

Incubation of the drug-sensitive H69, a small cell lung cancer cell line, with increased concentrations of adriamycin yielded multidrug resistant (MDR) H69AR cells that over-express multidrug resistance-associated protein (MRP1). MRP1 co-transports its substrate with glutathione (GSH), leading to lower intracellular GSH. In this report we tested whether depleting intracellular GSH in MRP1-expressing cells could hyper-sensitize them to anticancer drugs or not. We have found that the GSH contents in MRP1-expressing cells are significantly lower than their corresponding control cells. The treatment with MRP1 substrate verapamil or the GSH synthetase inhibitor buthionine sulfoxi-mine significantly reduced the intracellular GSH contents in MRP1-expressing cells. Interestingly, depleting intracellular GSH contents can hyper-sensitize the MRP1-cDNA transfected BHK cells to daunomycin, but not the adriamycin-selected H69AR cells. Further analyses indicated that anti-apoptotic factor Bcl2 might be a factor responsible for the fact that depleting intracellular GSH could not hyper-sensitize H69AR cells to daunomycin. We hypothesized that knocking down the expression of Bcl2 could hyper-sensitize H69AR cells to daunomycin. Interestingly, infection of H69AR cells with retroviral particles harboring Bcl2 interfering RNAi not only reduced the expression of Bcl2, but also many factors that contribute to MDR, such as Bcl-xl, MRP1 and ABCC3, etc., leading to the MDR H69AR cells more sensitive to daunomycin than the parental H69 cell. Thus, although the mechanisms of the down-regulation of the genes contributing to MDR remain to be elucidated, retroviral particles harboring Bcl2 interfering RNAi could be used as an alternative way to sensitize the MDR cancer cells to anticancer drugs.     

广谱抗真菌转基因水稻植株化学成分与结构动态变化

【背景】种植广谱抗真菌水稻可能会带来一定的环境生物安全问题,对其植株的化学成分进行实质等同性分析是转基因水稻安全性评价的重要内容之一。【方法】以表达广谱抗真菌蛋白转基因水稻转品1和转品8及其相应非转基因水稻七丝软粘的秸秆为研究材料,采用化学法和扫描电镜技术分析外源基因的导入对水稻秸秆化学成分以及组织显微结构的影响。【结果】（1）在整个生长发育过程中,广谱抗真菌转基因水稻转品1和转品8与其非转基因水稻七丝软粘叶片、叶鞘和茎的纤维素、半纤维素、木质素以及粗蛋白含量的变化趋势基本一致,且品种间化学成分的含量不存在显著差异。（2）广谱抗真菌转基因水稻叶片表皮的硅质瘤状结构以及气孔的形状和致密程度与其非转基因水稻七丝软粘相似;茎壁、厚壁组织、薄壁组织以及大小维管束的形态和分布情况未发生明显变化。【结论与意义】表达广谱抗真菌蛋白转基因水稻秸秆的化学成分和组织显微结构与非转基因水稻基本一致。这为广谱抗真菌转基因水稻的环境安全性评估提供了依据。