Project description:This study is a multicenter, open-label, dose-escalation Phase I clinical trial designed to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of live bacterium MNC-168 as a single oral agent in subjects with advanced malignant solid tumors. To explore the changes of biomarkers and intestinal flora related to curative effect, mechanism of action, safety and/or pathological mechanism.
Project description:Prosaposin encodes, in tandem, four small acidic activator proteins (saposins) with specificities for glycosphingolipids hydrolases in lysosomes. To explore the molecular mechanism(s) of disease progression, temporal transcriptome microarray analyses of cerebrum and cerebellum tissues were conducted using mRNA from three prosaposin deficiency mouse models: PS-NA (hypomorphic prosaposin deficiency), PS-/- (prosaposin null) and 4L/PS-NA (a V394L/V394L glucocerebrosidase mutation and PS-NA) mice. Our results indicate that regionally specific gene expression abnormalities preceded the histological and behavioral changes and CEBPD is a candidate regulator of brain disease in prosaposin deficiency. The alterations of gene expression are detected at birth and are more profound in cerebellum than cerebrum. Keywords: disease-state analysis
Project description:Prosaposin encodes, in tandem, four small acidic activator proteins (saposins) with specificities for glycosphingolipids hydrolases in lysosomes. To explore the molecular mechanism(s) of disease progression, temporal transcriptome microarray analyses of cerebrum and cerebellum tissues were conducted using mRNA from three prosaposin deficiency mouse models: PS-NA (hypomorphic prosaposin deficiency), PS-/- (prosaposin null) and 4L/PS-NA (a V394L/V394L glucocerebrosidase mutation and PS-NA) mice. Our results indicate that regionally specific gene expression abnormalities preceded the histological and behavioral changes and CEBPD is a candidate regulator of brain disease in prosaposin deficiency. The alterations of gene expression are detected at birth and are more profound in cerebellum than cerebrum. Experiment Overall Design: In order to increase the temporal resolution of expression profile in brain, the disease progression in those models were inverstigated in two regions of brains (cerebellum and cerebrum) at three or four time points according to the genotypes. PS-/-: new born (0d), 10 days (10d), 20 days (20d), 25 days (25d); PS-NA: new born, 4 weeks (4w), 12 weeks (12w), 18 weeks (18w); 4L/PS-NA: 4 weeks (4w), 12 weeks (12w), 18 weeks (18w). The data from those models were analyzed relative to the corresponding wild type at same time point (0d, 10d, 20d, 4w, 12w, 18w).
Project description:Global warming and heat stress belong to the most critical environmental challenges to agriculture worldwide, causing severe losses of major crop yields. In present study we report that the endophytic bacterium Enterobacter sp. SA187 protects Arabidopsis thaliana to heat stress. To understand the mechanisms at molecular level we performed RNA-seq
Project description:Regular exercise is believed to suppress cancer progression. However, the precise molecular mechanisms by which exercise prevents cancer development remain unclear. In this study, using a steatosis-associated liver cancer mouse model, we found that regular exercise at a speed of 18 m/min for 20 min daily suppressed liver cancer development. To explore the underlying mechanisms, we examined the gene expression profiles in the livers of the exercise and non-exercise groups. We extracted RNA from non-tumor and tumor tissues from each mouse liver and performed bulk RNA-seq analysis. The expressions of circadian genes, such as Per1 and Cry2, were upregulated in the exercise group. We further found that the expression of a series of E2F1 and c-Myc target genes that directly affect the proliferation of cancer cells was downregulated in the exercised group. However, the expression of these genes was transcriptionally unchanged but degraded at the post-translational level by exercise. Cry2, which is regulated by the Skp1-Cul1-FBXL3 (SCFFBXL3) ubiquitin ligase complex by binding to FBXL3, can form a complex with E2F1 and c-Myc, which we think is the mechanism to degrade them. Our study revealed a previously unknown mechanism by which exercise prevents cancer development.
Project description:Objective to explore the mechanism of STAT3 regulating PD-L1 expression at transcriptional level after LIFR overexpression in pancreatic cancer cells.
Project description:Rhizoremediation, the biotechnology of the utilization of rhizospheric microorganisms associated with plant roots for the elimination of soil contaminants, is based on the ability of microorganisms to metabolize nutrients from plant root exudates, in order to survive the stressful conditions of the rhizosphere, and thereby, to co-metabolize or even mineralize toxic environmental contaminants. Novosphingobium sp. HR1a is a bacterial strain able to degrade a wide variety of polycyclic aromatic hydrocarbons (PAHs). We have demonstrated that this bacterium is able to grow in vegetated microcosms and to eliminate phenanthrene in the presence of clover faster than in non-vegetated systems, establishing a positive interaction with clover. We have studied the molecular basis of this interaction by phenomic, metabolomic and transcriptomic analyses, demonstrating that the positive interaction between clover and Novosphingobium sp. HR1a is a result of the bacterial utilization of different carbon and nitrogen sources (such as sugars, amino acids and organic acids) released during seedling development, and the capacity of exudates to induce the PAH degradation pathway. These results are pointing out to Novosphingobium sp. HR1a as a promising strain for the bioremediation of PAH-contaminated soils.