A new trick for an old dog: The application of mifepristone in the treatment of adenomyosis

Adenomyosis is also called internal endometriosis and affects about 20% of reproductive‐aged women. It seriously reduces life quality of patients because current drug therapies face with numerous challenges. Long‐term clinical application of mifepristone exhibits wonderful therapeutic effects with mild side‐effects in many disorders since 1982. Since adenomyosis is a refractory disease, we investigate whether mifepristone can be applied in the treatment of adenomyosis. In this study, we investigated the direct effects of mifepristone on human primary eutopic endometrial epithelial cells and stromal cells in adenomyosis. We found that mifepristone causes cell cycle arrest through inhibiting CDK1 and CDK2 expressions and induces cell apoptosis via the mitochondria‐dependent signalling pathway in endometrial epithelial cells and stromal cells of adenomyosis. Furthermore, mifepristone inhibits the migration of endometrial epithelial cells and stromal cells through decreasing CXCR4 expression and restricts the invasion of endometrial epithelial cells via suppression of epithelial‐mesenchymal transition in adenomyosis. We also found that mifepristone treatment decreases the uterine volume, CA125 concentration and increases the haemoglobin concentration in serum for adenomyosis patients. Therefore, we demonstrate that mifepristone could serve as a novel therapeutic drug in the treatment of adenomyosis, and therefore, the old dog can do a new trick.     

An auto-inducible expression and high cell density fermentation of Beefy Meaty Peptide with Bacillus subtilis

Bioprocess and Biosystems Engineering - Currently, some cases about the expression of flavor peptides with microorganisms were reported owing to the obvious advantages of biological expression over...     

The auxin-inducible phosphate transporter AsPT5 mediates phosphate transport and is indispensable for arbuscule formation in Chinese milk vetch at moderately high phosphate supply

Phosphorus is a macronutrient that is essential for plant survival. Most land plants have evolved the ability to form a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, which enhances phosphate (Pi) acquisition. Modulation of Pi transporter systems is the master strategy used by mycorrhizal plants to adapt to ambient Pi concentrations. However, the specific functions of PHOSPHATE TRANSPORTER 1 (PHT1) genes, which are Pi transporters that are responsive to high Pi availability, are largely unknown. Here, we report that AsPT5, an Astragalus sinicus (Chinese milk vetch) member of the PHT1 gene family, is conserved across dicotyledons and is constitutively expressed in a broad range of tissues independently of Pi supply, but is remarkably induced by indole-3-acetic acid (auxin) treatment under moderately high Pi conditions. Subcellular localization experiments indicated that AsPT5 localizes to the plasma membrane of plant cells. Using reverse genetics, we showed that AsPT5 not only mediates Pi transport and remodels root system architecture but is also essential for arbuscule formation in A. sinicus under moderately high Pi concentrations. Overall, our study provides insight into the function of AsPT5 in Pi transport, AM development and the cross-talk between Pi nutrition and auxin signalling in mycorrhizal plants.     

The role of reactive oxygen species in the virulence of wheat leaf rust fungus Puccinia triticina

Reactive oxygen species (ROS) play an important role during host–pathogen interactions and are often an indication of induced host defence responses. In this study, we demonstrate for the first time that Puccinia triticina (Pt) generates ROS, including superoxide, H₂O₂ and hydroxyl radicals, during wheat infection. Through pharmacological inhibition, we found that ROS are critical for both Pt urediniospore germination and pathogenic development on wheat. A comparative RNA-Seq analysis of different stages of Pt infection process revealed 291 putative Pt genes associated with the oxidation–reduction process. Thirty-seven of these genes encode known proteins. The expressions of five Pt genes, including PtNoxA, PtNoxB, PtNoxR, PtCat and PtSod, were subsequently verified using RT-qPCR analysis. The results show that the expressions of PtNoxA, PtNoxB, PtNoxR, PtCat and PtSod are up-regulated during urediniospore germination. In comparison, the expressions of PtNoxA, PtNoxB, PtNoxR and PtCat are down-regulated during wheat infection from 12 to 120 h after inoculation (HAI), whereas the expression of PtSod is up-regulated with a peak of expression at 120 HAI. We conclude that ROS are critical for the full virulence of Pt and a coordinate down-regulation of PtNox genes may be important for successful infection in wheat.     

Genetic variants and underlying mechanisms influencing variance heterogeneity in maize

Traditional genetic studies focus on identifying genetic variants associated with the mean difference in a quantitative trait. Because genetic variants also influence phenotypic variation via heterogeneity, we conducted a variance‐heterogeneity genome‐wide association study to examine the contribution of variance heterogeneity to oil‐related quantitative traits. We identified 79 unique variance‐controlling single nucleotide polymorphisms (vSNPs) from the sequences of 77 candidate variance‐heterogeneity genes for 21 oil‐related traits using the Levene test (P < 1.0 × 10^?5). About 30% of the candidate genes encode enzymes that work in lipid metabolic pathways, most of which define clear expression variance quantitative trait loci. Of the vSNPs specifically associated with the genetic variance heterogeneity of oil concentration, 89% can be explained by additional linked mean‐effects genetic variants. Furthermore, we demonstrated that gene × gene interactions play important roles in the formation of variance heterogeneity for fatty acid compositional traits. The interaction pattern was validated for one gene pair (GRMZM2G035341 and GRMZM2G152328) using yeast two‐hybrid and bimolecular fluorescent complementation analyses. Our findings have implications for uncovering the genetic basis of hidden additive genetic effects and epistatic interaction effects, and we indicate opportunities to stabilize efficient breeding and selection of high‐oil maize (Zea mays L.).     

Correlations between glycolysis with clinical traits and immune function in bladder urothelial carcinoma

Background: Glycolysis was a representative hallmark in the tumor microenvironment (TME), and we aimed to explore the correlations between glycolysis with immune activity and clinical traits in bladder urothelial carcinoma (BLCA).Methods: Our study obtained glycolysis scores for each BLCA samples from TCGA by a single-sample gene set enrichment analysis (ssGSEA) algorithm, based on a glycolytic gene set. The relationship between glycolysis with prognosis, clinical characteristics, and immune function were investigated subsequently.Results: We found that enhanced glycolysis was associated with poor prognosis and metastasis in BLCA. Moreover, glycolysis had a close correlation with immune function, and enhanced glycolysis increased immune activities. In other words, glycolysis had a positive correlation with immune activities. Immune checkpoints such as IDO1, CD274, were up-regulated in high-glycolysis group as well.Conclusion: We speculated that in BLCA, elevated glycolysis enhanced immune function, which caused tumor cells to overexpress immune checkpoints to evade immune surveillance. Inhibition of glycolysis might be a promising assistant for immunotherapy in bladder cancer.     

The C‐degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes

Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino‐ or carboxyl‐termini are eliminated by the N‐ or C‐degron pathways, respectively. We aimed to elucidate the function of C‐degron pathways and to unveil how normal proteomes are exempt from C‐degron pathway‐mediated destruction. Our data reveal that C‐degron pathways remove mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. Furthermore, the C‐degron and N‐degron pathways cooperate in protein removal. Proteome analysis revealed a shortfall in normal proteins targeted by C‐degron pathways, but not of defective proteins, suggesting proteolysis‐based immunity as a constraint for protein evolution/selection. Our work highlights the importance of protein termini for protein quality surveillance, and the relationship between the functional proteome and protein degradation pathways.     

Silencing of ZFP36L2 increases sensitivity to temozolomide through G2/M cell cycle arrest and BAX mediated apoptosis in GBM cells

Molecular Biology Reports - Despite the advancements in primary brain tumour diagnoses and treatments, the mortality rate remains high, particularly in glioblastoma (GBM). Chemoresistance,...     

Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson’s Disease via the TLR4/PI3K/AKT/NF-κB Pathway Stimulated by α-Synuclein

Neurochemical Research - Gut microbiota is closely related to the Parkinson’s disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD...