Project description:Various bioactive food compounds may confer health and longevity benefits, possibly through altering or preserving the human epigenome. While bioactive food compounds are widely being marketed as ‘improving health and longevity’ by counteracting harmful effects of poor nutrition and lifestyle, claimed effects are often not adequately documented. Using the honey bee (Apis mellifera) as a model species, we here employed a multi-step screening approach to investigate seven compounds for effects on lifespan and DNA methylation using ELISA and whole genome bisulfite sequencing (WGBS). A positive longevity effect was detected for valproic acid, isovaleric acid, and cyanocobalamin. For curcumin, we found that lifespan shortening caused by ethanol intake, was restored when curcumin and ethanol were co-administered. Furthermore, we identified region specific DNA methylation changes as a result of ethanol intake. Ethanol specific changes in DNA methylation were fully or partially blocked in honey bees receiving ethanol and curcumin together. Ethanol-affected and curcumin-blocked differentially methylated regions covered genes involved in fertility, temperature regulation and tubulin transport. Our results demonstrate fundamental negative effects of low dose ethanol consumption on lifespan and associated DNA methylation changes and present a proof-of-principle on how longevity and DNA methylation changes can be negated by the bioactive food component curcumin. Our findings provide a fundament for further studies of curcumin in mice and humans and offer an avenue to explore regarding possible prevention of health issues related to alcohol consumption.
Project description:We conducted a comprehensive screening of bioactive compounds sourced from natural products, specifically targeting those capable of inducing apoptosis while inhibiting tyrosine kinase activity. Our investigation encompassed a diverse range of compounds, including pure compounds, compound mixtures, and peptides, all evaluated within the A549 cell line. To delve into the underlying molecular mechanisms, we employed phosphoproteomics analysis, which enabled us to comprehensively assess the impact of these bioactive compounds on cellular pathways. Through labeling digested proteins with distinct isobaric tags, we meticulously examined the cellular response to each compound. In our experimental design, we included two established chemical drugs, Afatinib and Osimertinib, serving as positive controls. These drugs, both kinase inhibitors utilized in cancer treatment, operate via distinct mechanisms and target different kinases. By comparing the effects of our test compounds with these controls, we aimed to elucidate their potential therapeutic relevance and mechanisms of action. Among the compounds examined were extracts from Phallus indusiatus and Fomes rimosus (Berk.) Cooke, as well as specific compounds like Chamuangone, Cannabigerol (CBG), Cannabidiol (CBD), and NP1-cyclic peptide
Project description:In this study, we investigated seven medicinal plant species from French Guiana as potential sources of novel antitubercular compounds. Using ultrasound-assisted extraction, liquid-liquid partitioning, and UHPLC-HRMS/MS, we created a library of 72 samples screened against Mycobacterium tuberculosis H37Ra. The most active fractions were the non-polar extracts from Indigofera suffruticosa, Tetradenia riparia, and Zingiber zerumbet.
Through bioactivity-guided molecular networking, we integrated metabolomic and bioassays data to prioritize and annotate active metabolites, primarily flavonoids. Computational tools (GNPS, SIRIUS, TIMA-R) further enhanced structural prediction and dereplication. This approach offers an efficient strategy to identify known and novel bioactive compounds without requiring exhaustive isolation.
Project description:Gastrointestinal discomfort is one of the most common issues during spaceflight, and there is currently a lack of targeted drug treatment strategies. Current research in this area focuses on single-factor modeling, lacking a comprehensive understanding. In the present study, we constructed space flight models based on most important two factors, microgravity and low-dose radiation. Histological, cellular and molecular analyses confirmed the advantage of this dual-factor model in simulating space flight-caused injuries. Upregulated inflammatory and homeostasis disruption were observed in intestines treated by these dual factors. Our data revealed that dual factors enhanced the migration of a Ccr7+ B cells into intestines through upregulating the expression of Cxcr4, which exerted strong activation regulations on leukocytes. We further validated that bioactive compounds of CB001 effectively alleviated intestinal perturbations through recovering the expression of tight junction proteins, suppressing the migration of B cells and downregulating the levels of pro-inflammatory cytokines. Collectively, our work offered CB001 compounds as candidate intervention drug for space flight-induced intestine dysfunctions based on a dual-factor mice model. These data shed lights on special medicine screening for health protection in space flight.
Project description:Gastrointestinal discomfort is one of the most common issues during spaceflight, and there is currently a lack of targeted drug treatment strategies. Current research in this area focuses on single-factor modeling, lacking a comprehensive understanding. In the present study, we constructed space flight models based on most important two factors, microgravity and low-dose radiation. Histological, cellular and molecular analyses confirmed the advantage of this dual-factor model in simulating space flight-caused injuries. Upregulated inflammatory and homeostasis disruption were observed in intestines treated by these dual factors. Our data revealed that dual factors enhanced the migration of a Ccr7+ B cells into intestines through upregulating the expression of Cxcr4, which exerted strong activation regulations on leukocytes. We further validated that bioactive compounds of CB001 effectively alleviated intestinal perturbations through recovering the expression of tight junction proteins, suppressing the migration of B cells and downregulating the levels of pro-inflammatory cytokines. Collectively, our work offered CB001 compounds as candidate intervention drug for space flight-induced intestine dysfunctions based on a dual-factor mice model. These data shed lights on special medicine screening for health protection in space flight.
Project description:Exploring the therapeutic effects of bioactive compounds has been traditionally approaching by phenotypic screenings followed by functional validation by in vitro assays. The thermal proteome profiling (TPP) has been successfully applied to study drug targets and off-target. We applied a modified protocol based on TPP to elucidate the mechanism of actions (MOA)s of novel bioactives compounds from marine biodiscovery. We have modified the method to gain the specificity for its application to compounds with limited chemical or structural characterization. Method implementation includes increasing the centrifugation force to precipitate the microsomal fraction previous to the thermal shift assay. The range of temperatures has been reduced to optimize the analysis without compromising resolution. Finally, the mass spectrometry analysis was based on label-free quantitative proteomics. Comparison of the targets among methodologies confirmed that the precipitation of the microsomal membranes before TPP is an essential step to discriminate between true targets from proteins precipitates after subcellular fractionation by centrifugation force. As a probe of concept, a novel marine bioactive compound has been analyzed on the hepatic cell line HepG2. We found that 2 targets proteins, aldehyde dehydrogenase and isocitrate dehydoregenase, can be related with beneficial properties towards obesity and obesity-related comorbidities. Identification of targets is key to decipher the MOAs of bioactive compound, predict the mode of action as well as possible harmful effects.
Project description:We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. We tested several of these in duplicate replicates in blasts from a patient with APL. Also included in this data set are a collection of 6 primary patient AML cells, 3 normal neutrophils samples, and 3 normal monocyte samples. This data was used to evaluate whole genome effects of the compounds on APL cells in relation to AML versus normal neutrophils and monocytes. Keywords = Leukemia Keywords = APL Keywords = AML Keywords = chemical genomics Keywords: repeat sample
Project description:We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we prioritized 15 candidate compounds (2 were already confirmed in the literature). We next evaluated the 13 remaining compounds. Eight reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. This data set contains HL-60 cells treated in replicates of 3 with the original 13 selected candidates. It also contains 6 untreated, 6 DMSO treated, 3 ATRA treated, 3 PMA treated, and 3 1,25-dihydroxyvitamin D3 treated HL-60 controls. In addition, it contains 3 neutrophil and 3 monocyte samples from distinct normal human donors and 9 primary patient AML samples. This data set was used to evaluate the whole genome effects of the candidate compounds on HL-60 cells. Keywords = AML Keywords = leukemia Keywords = HL-60 Keywords = chemical genomics Keywords: repeat sample