RETRACTED ARTICLE: Silencing SP1 Alleviated Sevoflurane-Induced POCD Development via Cholinergic Anti-inflammatory Pathway

Neurochemical Research - Postoperative cognitive dysfunction (POCD) is a common complication induced by anesthesia or surgery, which affects the concentration, cognition and memory of patients....     

过表达pps基因和aroG~(fbr)基因对北京棒杆菌L-色氨酸合成的影响

【目的】通过增加北京棒杆菌(Corynebacterium pekinense)PD-67芳香族氨基酸合成的前体物质磷酸烯醇式丙酮酸(PEP)的供应,解除终产物对芳香族氨基酸合成途径中第一个酶同时也是关键酶3-脱氧-D-阿拉伯庚酮糖-7-磷酸合酶(DS)的反馈抑制并提高抗反馈抑制的DS的活力,使碳流更多地流向芳香族氨基酸合成途径,从而积累更多L-色氨酸。【方法】运用PCR技术扩增北京棒杆菌PD-67磷酸烯醇式丙酮酸合酶基因pps,与表达载体连接构建重组质粒pXPS;运用重叠PCR技术定点突变大肠杆菌(Escherichia coli)受苯丙氨酸调控的DS基因aroG,使相应的编码氨基酸序列发生突变:Leu175Asp,新的基因命名为aroGfbr,与表达载体连接构建重组质粒pXA;构建pps和aroGfbr的共表达重组质粒pXAPS。将3个重组质粒分别转入菌株PD-67,构建工程菌株PD-67/pXPS、PD-67/pXA和PD-67/pXAPS。通过摇瓶发酵研究工程菌株的发酵特性。【结果】酶活分析结果表明,pps基因和aroGfbr基因在北京棒杆菌PD-67中均实现了表达。工程菌株PD-67/pXA粗酶液DS抗反馈抑制分析表明,AroGfbr已解除酪氨酸和苯丙氨酸的反馈抑制。过表达pps基因和aroGfbr基因分别使工程菌L-色氨酸产量提高12.1%和26.8%,双基因共表达可使工程菌的产酸量提高35.9%。【结论】北京棒杆菌PD-67pps基因的过表达以及大肠杆菌来源的解除反馈抑制的aroGfbr的过表达均有助于增加PD-67 L-色氨酸的合成,而双基因的共表达可以进一步提高L-色氨酸的积累量。     

Prognostic Significance and Molecular Mechanism of ATP-Binding Cassette Subfamily C Member 4 in Resistance to Neoadjuvant Radiotherapy of Locally Advanced Rectal Carcinoma

Background

Mechanism of radioresistance in rectal carcinoma remains largely unknown. We aimed to evaluate the predictive role of ATP-binding cassette subfamily C member 4 (ABCC4) in locally advanced rectal carcinoma and explore possible molecular mechanisms by which ABCC4 confers the resistance to neoadjuvant radiotherapy.

Methods

The expression of ABCC4 and P53 mutant in biopsy tissue specimens from 121 locally advanced rectal carcinoma patients was examined using immunohistochemistry. The factors contributing to 3-year overall survival and disease-free survival were evaluated using the Kaplan-Meier method and Cox proportional hazard model. Lentivirus-mediated small hairpin RNA was applied to inhibit ABCC4 expression in colorectal carcinoma cell line RKO, and investigate the radiosensitivity in xenograft model. Intracellular cyclic adenosine monophosphate concentration and cell cycle distribution following irradiation were detected.

Results

High expression of ABCC4 and p53 mutant in pretreated tumors, poor pathological response, and high final tumor staging were significant factors independently predicted an unfavorable prognosis of locally advanced rectal carcinoma patients after neoadjuvant radiotherapy. Down-regulation of ABCC4 expression significantly enhanced irradiation-induced suppression of tumor growth in xenograft model. Furthermore, down-regulation of ABCC4 expression enhanced intracellular cyclic adenosine monophosphate production and noticeable deficiency of G1-S phase checkpoint in cell cycle following irradiation.

Conclusions

Our study suggests that ABCC4 serves as a novel predictive biomarker that is responsible for the radioresistance and predicts a poor prognosis for locally advanced rectal carcinoma after neoadjuvant radiotherapy.     

Microarray Analysis of Gene Expression Profiles of Schistosoma japonicum Derived from Less-Susceptible Host Water Buffalo and Susceptible Host Goat

Background

Water buffalo and goats are natural hosts for S. japonicum in endemic areas of China. The susceptibility of these two hosts to schistosome infection is different, as water buffalo are less conducive to S. japonicum growth and development. To identify genes that may affect schistosome development and survival, we compared gene expression profiles of schistosomes derived from these two natural hosts using high-throughput microarray technology.

Results

The worm recovery rate was lower and the length and width of worms from water buffalo were smaller compared to those from goats following S. japonicum infection for 7 weeks. Besides obvious morphological difference between the schistosomes derived from the two hosts, differences were also observed by scanning and transmission electron microscopy. Microarray analysis showed differentially expressed gene patterns for parasites from the two hosts, which revealed that genes related to lipid and nucleotide metabolism, as well as protein folding, sorting, and degradation were upregulated, while others associated with signal transduction, endocrine function, development, immune function, endocytosis, and amino acid/carbohydrate/glycan metabolism were downregulated in schistosomes from water buffalo. KEGG pathway analysis deduced that the differentially expressed genes mainly involved lipid metabolism, the MAPK and ErbB signaling pathways, progesterone-mediated oocyte maturation, dorso-ventral axis formation, reproduction, and endocytosis, etc.

Conclusion

The microarray gene analysis in schistosomes derived from water buffalo and goats provide a useful platform to disclose differences determining S. japonicum host compatibility to better understand the interplay between natural hosts and parasites, and identify schistosome target genes associated with susceptibility to screen vaccine candidates.     

采煤沉陷裂缝区土壤含水量变化对柠条叶片叶绿素荧光的响应

采煤塌陷引起的土壤环境因子的变化对矿区植物生长的影响越来越受到人们的关注,快速叶绿素荧光诱导动力学分析技术被称为植物受胁迫状态的有效探针,能够快速获取胁迫下光系统II光化学活性和电子传递的信息。研究采煤塌陷裂缝区植物叶片叶绿素荧光的变化是揭示煤炭开采塌陷胁迫对植物个体生长影响的关键环节,能为大尺度下采煤沉陷区植物损伤机理研究提供基础。对于黄土高原半干旱矿区,土壤水分无疑是植物生长最重要的限制因素,而植物叶片叶绿素荧光变化采煤塌陷影响下土壤含水量变化的响应如何尚不清楚。为了弄清采煤沉陷裂缝影响下土壤含水量变化对柠条叶片叶绿素荧光响应的影响,选取神东煤田大柳塔矿区52302工作面为实验场地,在分析了采煤塌陷裂缝对土壤含水量的影响的基础上,以生态修复物种柠条为研究对象,对采煤塌陷裂缝区不同土壤含水量下柠条叶片快速叶绿素荧光诱导动力学曲线进行监测。结果显示:(1)由于煤炭井工开采在地表形成大量裂缝,破坏了土体结构,增加了土壤水分的蒸发面,加速了土壤水的散失。土壤水分含量随着与裂缝之间距离的增加而增加,从距离裂缝0 cm到300 cm,土壤平均含水量从5.63%增加到15.07%;(2)裂缝区土壤水分降低,柠条受到干旱胁迫程度加重,叶片快速叶绿素荧光诱导动力学曲线由O—J—I—P变形为O—K—J—I—P曲线。干旱胁迫通过干扰柠条叶片PSII电子供体侧、受体侧以及电子传递链的功能,严重的损害了柠条叶片光合机构的正常功能。     

Prevention of Schistosoma japonicum infection in mice with long-acting praziquantel implants

This work reports the prevention outcomes of a praziquantel (PZQ) implant against the infection of Schistosoma japonicum in mice. The PZQ implant produced stable plasma PZQ concentrations in a range of 100-1300 ng/mL for a period of 70 days, by releasing PZQ in subcutaneous tissues in a sustained manner. To assess the prevention effects, the mice were infected at varying times after implantation. All the mice were sacrificed at 6 weeks after infection for worm and egg recovery and counting, worm morphological examination, determination of egg-hatching rates, and analysis of hepatic histology. The infection was successfully prevented for mice with early infection times (within 2-3 weeks), as nearly no worms, paired worms, eggs, or miracidia were recovered. However, in mice with late infection times (after 3 weeks), the prevention effects were diminished due to the decreased plasma PZQ concentrations at late times. Interestingly, the implants showed robust prevention effects on repeated infection at 1 and 3 weeks. In the infection-prevented mouse livers, no granuloma formation or granulomatous inflammation was observed. The results demonstrated that by blocking the development of infecting miracidia and by deactivating the eggs, the PZQ implants encouragingly prevented the S. japonicum infection and avoided liver damage.     

Schistosoma japonicum: treatment of different developmental stages in mice with long-acting praziquantel implants

This paper reports the effective treatment of Schistosoma japonicum in a mouse model with long-acting praziquantel (PZQ)-loaded poly(ε-caprolactone) implants. The implants yielded stable, high plasma PZQ concentrations ranging 100–1600 ng/mL during the 40-day investigation period. For assessment of efficacy, the implants were implanted into mice immediately after infection and at 1, 2, 3 and 4 weeks after infection to treat the schistosomes at different developmental stages. All the mice were sacrificed at 6 weeks after infection for worm and egg recovery, worm morphology examination, and histopathological analysis of implantation site tissues. The worm burdens, egg burdens, and numbers of miracidia hatched from the retrieved eggs for all the implant-treated groups (except groups T2-A, T4 and T5) were reduced by 100% when compared with the control group. From groups T2-A, T4 and T5, some schistosome debris was recovered. Eggs were found in only group T5 for which the time between infection and implantation was 4 weeks, which enabled the maturation of juvenile female schistosomes into adult ones that lay eggs. Histopathological observations of implantation tissue showed no evidence of granulomatous foreign-body or lymphoid cell aggregation, demonstrating good biocompatibility of the PZQ implants. These results demonstrate that the long-acting PZQ implants can kill schistosomes at any developmental stages and attenuate/avoid the associated liver damage.     

The progress of silver nanoparticles in the antibacterial mechanism, clinical application and cytotoxicity

Nanotechnology is a highly promising field, with nanoparticles produced and utilized in a wide range of commercial products. Silver nanoparticles (AgNPs) has been widely used in clothing, electronics, bio-sensing, the food industry, paints, sunscreens, cosmetics and medical devices, all of which increase human exposure and thus the potential risk related to their short- and long-term toxicity. Many studies indicate that AgNPs are toxic to human health. Interestingly, the majority of these studies focus on the interaction of the nano-silver particle with single cells, indicating that AgNPs have the potential to induce the genes associated with cell cycle progression, DNA damage and mitochondrial associated apoptosis. AgNPs administered through any method were subsequently detected in blood and were found to cause deposition in several organs. There are very few studies in rats and mice involving the in vivo bio-distribution and toxicity, organ accumulation and degradation, and the possible adverse effects and toxicity in vivo are only slowly being recognized. In the present review, we summarize the current data associated with the increased medical usage of nano-silver and its related nano-materials, compare the mechanism of antibiosis and discuss the proper application of nano-silver particles.     

Characterization of VAMP2 in Schistosoma japonicum and the Evaluation of Protective Efficacy Induced by Recombinant SjVAMP2 in Mice

Background

The outer-tegument membrane covering the schistosome is believed to maintain via the fusion of membranous vesicles. Fusion of biological membranes is a fundamental process in all eukaryotic cells driven by formation of trans-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes through pairing of vesicle associated v-SNAREs (VAMP) with complementary t-SNAREs on target membranes. The purpose of this study was to characterize Schistosoma japonicum vesicle-associated membrane protein 2 (SjVAMP2) and to investigate its potential as a candidate vaccine against schistosomiasis.

Methodology/Principal Findings

The sequence of SjVAMP2 was analyzed, cloned, expressed and characterized. SjVAMP2 is a member of the synaptobrevin superfamily harboring the v-SNARE coiled-coil homology domain. RT–PCR analysis revealed that significantly higher SjVAMP2 levels were observed in 14-, 28- and 42-day-old worms, and SjVAMP2 expression was much higher in 42-day-old female worms than in those male worms. Additionally, the expression of SjVAMP2 was associated with membrane recovery in PZQ-treated worms. Immunostaining assay showed that SjVAMP2 was mainly distributed in the sub-tegument of the worms. Western blotting revealed that rSjVAMP2 showed strong immunogenicity. Purified rSjVAMP2 emulsified with ISA206 adjuvant induced 41.5% and 27.3% reductions in worm burden, and 36.8% and 23.3% reductions in hepatic eggs in two independent trials. Besides, significantly higher rSjVAMP2-specific IgG, IgG1, IgG2a levels were detected in rSjVAMP2-vaccinated mice.

Conclusion

Our study indicated that SjVAMP2 is a potential vaccine candidate against S. japonicum and provided the basis for further investigations into the biological function of SjVAMP2.