Histopathological studies ofSporothrix schenckii-inoculated mice

Defense mechanisms againstSporothrix schenckii were studied using mouse models. After an intracutaneous injection of the yeast form ofS. schenckii to the dorsal skin of the congenitally athymic nude and normal heterozygote littermate mice, nodules were formed. They regressed and disappeared in 10 weeks in the case of normal mice. On the other hand, nodules and then ulceration developed progressively in nude mice until all animals expired by dissemination of microorganisms at the 11th week of inoculation. Histopathologically the migrated cells were similar in both the normal and the nude mice, particularly during the early phase (within 24 h), with infiltration by PMNs being predominant. Fragmentation ofS. schenckii commenced early during the 12–24 h stage of inoculation in the normal mice, while such fragmentation was scarce in nude mice even though numerous PMNs accumulated. Microscopic observations in the early stages (within 24 h of inoculation) suggested that the lack of killing activity by PMNs in nude mice contributes more to the impaired defense than the lack of macrophage activation by T-cells.     

The emerging role of circular RNAs in cardiovascular diseases

Journal of Physiology and Biochemistry - Cardiovascular disease (CVD) is one of the vital causes of morbidity and mortality, and the number of deaths from CVD has increased worldwide. Circular RNAs...     

Elements in Lung Tissues of Patients from a High Lung Cancer Incidence Area of China

The concentrations of trace elements are closely related to tumor genesis, progression, and therapy. In order to establish the extent to which trace elements apply to lung cancer, 15 trace elements were determined in 60 lung tissue samples from residents of Xuanwei and Fuyuan, two counties with extremely high lung cancer incidences in Yunnan province, China. The results indicated that the levels of V, Fe, Zn, Cd, Ni, Cu, Se, and Pb in the lung cancer tissues were significantly different from those in benign tissues. Among the eight elements, the levels of V, Fe, Zn, and Cd in the lung cancer tissues were lower than those in the benign tissues, while those of Ni, Cu, Se, and Pb were higher. Multiple conditional logistic regression showed that among the 15 elements, Cu, Pb (β > 0, OR > 1), and Zn (β < 0, OR < 1) were closely related to the lung cancer. Cu and Pb were classified as risk factors for local lung cancer and Zn was identified as a protective factor. The results obtained will provide dietary suggestions in terms of how to reduce lung cancer risks by appropriately balancing the intakes of certain trace elements especially for individuals who are from those two counties.     

CpG_MPs: identification of CpG methylation patterns of genomic regions from high-throughput bisulfite sequencing data

High-throughput bisulfite sequencing is widely used to measure cytosine methylation at single-base resolution in eukaryotes. It permits systems-level analysis of genomic methylation patterns associated with gene expression and chromatin structure. However, methods for large-scale identification of methylation patterns from bisulfite sequencing are lacking. We developed a comprehensive tool, CpG_MPs, for identification and analysis of the methylation patterns of genomic regions from bisulfite sequencing data. CpG_MPs first normalizes bisulfite sequencing reads into methylation level of CpGs. Then it identifies unmethylated and methylated regions using the methylation status of neighboring CpGs by hotspot extension algorithm without knowledge of pre-defined regions. Furthermore, the conservatively and differentially methylated regions across paired or multiple samples (cells or tissues) are identified by combining a combinatorial algorithm with Shannon entropy. CpG_MPs identified large amounts of genomic regions with different methylation patterns across five human bisulfite sequencing data during cellular differentiation. Different sequence features and significantly cell-specific methylation patterns were observed. These potentially functional regions form candidate regions for functional analysis of DNA methylation during cellular differentiation. CpG_MPs is the first user-friendly tool for identifying methylation patterns of genomic regions from bisulfite sequencing data, permitting further investigation of the biological functions of genome-scale methylation patterns.     

Evaluation of swollenin from <Emphasis Type="Italic">Trichoderma pseudokoningii</Emphasis> as a potential synergistic factor in the enzymatic hydrolysis of cellulose with low cellulase loadings

Swollenin is a novel plant expansin-like protein that has been proposed to have a cellulose disruption activity. In this study, the recombinant swollenin (SWO2) from Trichoderma pseudokoningii S38 was successfully produced and purified in Aspergillus niger with a final yield of up to 10 mg of purified protein from 1 l of fermentation supernatant. The recombinant protein was found to exhibit very low level of endoglucanase activity and caused a slight increase in the crystallinity when treating cellulose. Simultaneous incubation of SWO2 with low-dose cellulases resulted in a significant synergistic activity in cellulose hydrolysis. Specifically, an even greater increase in the synergistic activity was obtained when cellulose was pretreated with swollenin followed by cellulase hydrolysis. Our results, therefore, provide a novel approach for the potential application of swollenin in the efficient saccharification of cellulosic materials.     

Role of glial cell line-derived neurotrophic factor in perineural invasion of pancreatic cancer

Perineural invasion (PNI) is the initial infiltration of tumor cells into the retroperitoneal nerve plexus and along the nerves. It precludes curative resection, is thought to be the major cause of local recurrence following resection, and is a special metastatic route in pancreatic cancer. Glial cell line-derived neurotrophic factor (GDNF) was recently recognized as a key player in the PNI process. This review covers the most recently published studies on the role of GDNF in pancreatic cancer. We introduce the players in PNI, summarize the distribution of GDNF and its receptors in pancreatic cancer, and discuss the effects and underlying mechanism of GDNF in the PNI process. Finally, we also review some potential inhibitors for GDNF-targeted therapy.     

Design,synthesis and biological evaluation of novel human monoamine oxidase B inhibitors based on a fragment in an X-ray crystal structure

Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC₅₀?=?3?nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems.