Project description:C elegans worms were exposed to either honokiol or magnolol and global transcriptomic profiles determied to eludicate potential modes of action
Project description:Recent research has highlighted that the polyphenols Quercetin (Q) and Tannic acid (TA) are capable of extending the lifespan of C. elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to Quercetin or Tannic acid concentrations that are non-effective (in lifespan extension), lifespan extending or toxic.
Project description:Bacteria use a variety of mechanisms, such as two‐component regulatory systems (TCSs), to rapidly sense and respond to distinct conditions and signals in their host organisms. For example, a type III secretion system (T3SS) is the key determinant of the virulence of the model plant pathogen Pseudomonas syringae and contains the TCS RhpRS as a key regulator. However, the signal sensed by RhpRS remains unknown. We found that RhpRS directly senses plant-generated polyphenols and responds by switching off P. syringae T3SS via crosstalk with alternative histidine kinases. Through a chemical screen, we identified three natural polyphenols (tannic acid, 1,2,3,4,6-pentagalloylglucose and epigallocatechin gallate) that induced the expression of the rhpRS operon in a RhpS-dependent manner.
Project description:Recent research has highlighted that the polyphenols Quercetin (Q) and Tannic acid (TA) are capable of extending the lifespan of C. elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to Quercetin or Tannic acid concentrations that are non-effective (in lifespan extension), lifespan extending or toxic. The global transcriptome was compared in wild type nematodes raised in the presence of 0, 50, 100, and 200 µM Quercetin (Q) or 0, 100, 200, and 300 µM Tannic acid (TA).
Project description:Although stimulating microglia to phagocytose abnormally infiltrated cells and tissue debris is crucial for improving the prognosis of ischemic stroke, this energy-intensive physiological process is hindered by the cerebral artery block-induced oxygen/ glucose deprivation. AMP-activated protein kinase (AMPK), as a key molecule regulating energy metabolism, shows promise in resolving this dilemma by elevating intracellular ATP levels in microglia. Here, we uncovered that while activation of AMPK can enhance energy metabolism, it also induces mitochondrial damage via reactive oxygen species (ROS), which demonstrates its double-edged effect. Based on this, from the library of natural polyphenols, gallic acid and ellagic acid were screened for their ability to effectively activate AMPK and scavenge ROS, and exhibit therapeutic effects in a photothrombotic (PT) stroke model. To overcome the poor bioavailability and targeting capability of natural polyphenols, we constructed a class of metal-organic frameworks (MOFs) as neuroprotective agents, which are formed by coordinating gallic acid with metal ions. Microglia benefiting from these MOFs exhibit more efficient phagocytosis, lower ROS levels, and higher cell viability. In a PT stroke model, stereotaxic injection of MOFs significantly increased microglial phagocytosis, provided superior neuronal protection, and improved behavioral outcomes. This strategy highlights the potential of natural polyphenols as neuroprotective agents and emphasizes the complexity and feasibility of regulating microglial phagocytosis via AMPK activation to promote stroke recovery, offering valuable insights into improving prognosis.
Project description:This set of arrays contains all microarray experiments done involving comparisons among C. elegans natural isolates and mutation-accumulation lines. Abstract: The evolutionary importance of gene-expression divergence is unclear: some studies suggest that it is an important mechanism for evolution by natural selection, whereas others claim that most between-species regulatory changes are neutral or nearly neutral. We examined global transcriptional divergence patterns in a set of Caenorhabditis elegans mutation-accumulation lines and natural isolate lines to provide insights into the evolutionary importance of transcriptional variation and to discriminate between the forces of mutation and natural selection in shaping the evolution of gene expression. We detected the effects of selection on transcriptional divergence patterns and characterized them with respect to coexpressed gene sets, chromosomal clustering of expression changes and functional gene categories. We directly compared observed transcriptional variation patterns in the mutation-accumulation and natural isolate lines to a neutral model of transcriptome evolution to show that strong stabilizing selection dominates the evolution of transcriptional change for thousands of C. elegans expressed sequences. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Computed
Project description:This set of arrays contains all microarray experiments done involving comparisons among C. elegans natural isolates and mutation-accumulation lines. Abstract: The evolutionary importance of gene-expression divergence is unclear: some studies suggest that it is an important mechanism for evolution by natural selection, whereas others claim that most between-species regulatory changes are neutral or nearly neutral. We examined global transcriptional divergence patterns in a set of Caenorhabditis elegans mutation-accumulation lines and natural isolate lines to provide insights into the evolutionary importance of transcriptional variation and to discriminate between the forces of mutation and natural selection in shaping the evolution of gene expression. We detected the effects of selection on transcriptional divergence patterns and characterized them with respect to coexpressed gene sets, chromosomal clustering of expression changes and functional gene categories. We directly compared observed transcriptional variation patterns in the mutation-accumulation and natural isolate lines to a neutral model of transcriptome evolution to show that strong stabilizing selection dominates the evolution of transcriptional change for thousands of C. elegans expressed sequences. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Keywords: all_pairs
Project description:Natural genetic variation is the raw material of evolution and influences disease development and progression. To analyze the effect of the genetic background on protein expression in the nematode C. elegans (Caenorhabditis elegans), the two genetically highly divergent wild-type strains N2 (Bristol) and CB4856 (Hawaii) were compared quantitatively. In total, we quantified 3,238 unique proteins in three independent SILAC (stable isotope labeling by amino acids in cell culture) experiments. The differentially expressed proteins were enriched for genes that function in insulin-signaling and stress response pathways.
Project description:To decipher the beneficial effects of Polyphenols on health, healthy volunteers were randomized into two groups and were submitted to either a red grape polyphenol rich extract supplemented diet (PP) or a placebo diet (PCB) during 8 weeks. Then they were submitted to a fructose load (3g/kg Fat Free Mass/day) during 7 days. Muscle biopsies were taken before the protocol, 8 weeks after PP or PCB diet and after the 7 days fructose load. We have employed whole genome microarray expression profiling as a discovery platform to identify genes regulated by fructose and to identify the mechanism of action of Polyphenols.