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opencc-zeroNov 2020View details →

Roundup causes embryonic development failure, alters metabolic pathways and gut microbiota functionality in non-target species

Background: Research around the weedkiller Roundup is among the most contentious of the 21st century. Scientists have provided inconclusive evidence that the weedkiller causes cancer and other life-threatening diseases, while industry-paid research reports that the weedkiller has no adverse effect on humans or animals. Much of the controversial evidence on Roundup is rooted in the approach used to determine safe use of chemicals, defined by outdated toxicity tests.We apply a system biology approach to the biomedical and ecological model species Daphnia to quantify the impact of Glyphosate and of its commercial formula, Roundup, on fitness, genome-wide transcription and gut microbiota, taking full advantage of clonal reproduction in Daphnia. We then apply machine learning-based statistical analysis to identify and prioritize correlations between genome-wide transcriptional and microbiota changes. Results: We demonstrate that chronic exposure to ecologically relevant concentrations of Glyphosate and Roundup at the approved regulatory threshold for drinking water in the US induce embryonic developmental failure, significant DNA damage (genotoxicity), and interfere with signaling. Furthermore, chronic exposure to the weedkiller alters the gut microbiota functionality and composition interfering with carbon and fat metabolism, as well as homeostasis. Using the 'Reactome', we identify conserved pathways across the Tree of Life, which are potential targets for Roundup in other species, including liver metabolism, inflammation pathways and collagen degradation, responsible for the repair of wounds and tissue remodeling. Conclusions: Our results show that chronic exposure to concentrations of Roundup and Glyphosate at the approved regulatory threshold for drinking water causes embryonic development failure, and alteration of key metabolic functions via direct effect on the host molecular processes and indirect effect on the gut microbiota. The ecological model species Daphnia occupies a central position in the food web of aquatic ecosystems, being the preferred food of small vertebrates and invertebrates as well as a grazer of algae and bacteria. The impact of the weedkiller on this keystone species has cascading effects on aquatic food webs, affecting their ability to deliver critical ecosystem services.

opencc-zeroAug 2019View details →

Data from: Exposure to environmental radionuclides is associated with altered metabolic and immunity pathways in a wild rodent

Wildlife inhabiting environments contaminated by radionuclides face putative detrimental effects of exposure to ionizing radiation, with biomarkers such as an increase in DNA damage and/or oxidative stress commonly associated with radiation exposure. To examine the effects of exposure to radiation on gene expression in wildlife, we conducted a de novo RNA sequencing study of liver and spleen tissues from a rodent, the bank vole Myodes glareolus. Bank voles were collected from the Chernobyl Exclusion Zone (CEZ), where animals were exposed to elevated levels of radionuclides, and from uncontaminated areas near Kyiv, Ukraine. Counter to expectations, we did not observe a strong DNA damage response in animals exposed to radionuclides, although some signs of oxidative stress were identified. Rather, exposure to environmental radionuclides was associated with upregulation of genes involved in lipid metabolism and fatty acid oxidation in the livers – an apparent shift in energy metabolism. Moreover, using stable isotope analysis, we identified that fur from bank voles inhabiting the CEZ had enriched isotope values of nitrogen: such an increase is consistent with increased fatty acid metabolism, but also could arise from a difference in diet or habitat between the CEZ and elsewhere. In livers and spleens, voles inhabiting the CEZ were characterized by immunosuppression, such as impaired antigen processing, and activation of leukocytes involved in inflammatory responses. In conclusion, exposure to low dose environmental radiation impacts pathways associated with immunity and lipid metabolism, potentially as a stress-induced coping mechanism.

opencc-by-4.0Mar 2024View details →

Uncoupling of Behavioral and Metabolic Twenty-Four-Hour Rhythms in Reindeer (Current Biology, Meier et al. 2024): Metabolomics analysis tables: Annotation list, pathway analysis outputs, target list for targeted peak exstraction and MS/MS spectra of annotated features

Metabolomics analysis tables: Annotation list, pathway analysis outputs, target list for targeted peak exstraction and MS/MS spectra of annotated features

opencc-by-4.0Dec 2021View details →

Datasets: Carbon sources and pathways for citrate secreted by human prostate cancer cells determined by NMR tracing and metabolic modeling

Zipped NMR datasets: data1     LNCaP medium with [U-13C4]aspartate data2     LNCaP medium with [1,6-13C2]glucose data3     LNCaP medium with [2-13C]pyruvate data4     VCaP medium with [1,6-13C2]glucose data5     VCaP medium with [U-13C4]aspartate -glucose +pyruvate data6     VCaP medium with [5-13C]glutamine data7     VCaP medium with [2-13C]pyruvate -glucose +aspartate data8     VCaP medium with [5-13C]glutamine data9     VCaP medium with [5-13C]glutamine data10  VCaP medium with [5-13C]glutamine data11  LNCaP and VCaP medium with and without zinc(II) data12  LNCaP and VCaP medium with and without zinc(II) data13  LNCaP and VCaP medium with and without zinc(II) data14  LNCaP medium with [U-13C4]aspartate -glucose +pyruvate data15  LNCaP medium with [5-13C]glutamine data16  LNCaP medium with [2-13C]pyruvate data17  LNCaP medium with [5-13C]glutamine data18  VCaP medium with [1,6-13C2]glucose data19  VCaP medium with [1,6-13C2]glucose data20  VCaP medium with [2-13C]pyruvate data21  LNCaP medium with [2-13C]pyruvate data22  LNCaP medium with [2-13C]pyruvate +citr. Spiking data23  LNCaP medium with [5-13C]glutamine data24  LNCaP medium with [5-13C]glutamine data25  LNCaP medium with [2-13C]pyruvate data26  VCaP medium with [2-13C]pyruvate data27  VCaP medium with [2-13C]pyruvate -glucose +aspartate data28  VCaP medium with [U-13C4]aspartate -glucose +pyruvate data29  LNCaP medium with [2-13C]pyruvate data30  LNCaP medium with [2-13C]pyruvate data31  LNCaP medium with [2-13C]pyruvate data32  VCaP medium with [2-13C]pyruvate -glucose +aspartate data33  VCaP medium with [U-13C4]aspartate -glucose +pyruvate data34  VCaP medium with [U-13C4]aspartate -glucose +pyruvate data35  LNCaP medium with [U-13C4]aspartate data36  VCaP medium with [U-13C4]aspartate -glucose +pyruvate data37  LNCaP medium with [5-13C]glutamine + citr. spiking

opencc-zeroAug 2022View details →

miR-1285-3p targets TPI1 to regulate the glycolysis metabolism signaling pathway of Tibetan sheep Sertoli cells

Glycolysis in sertoli cells (SCs) can provide energy substrates for the development of spermatogenic cells. Triose phosphate isomerase 1 (TPI1) is one of the key catalytic enzymes involved in glycolysis. However, the biological function of TPI1 in SCs and its role in glycolytic metabolic pathways are poorly understood. On the basis of previous research, we isolated primary SCs from Tibetan sheep and overexpressed TPI1 gene to determine its effect on the proliferation, glycolysis, and apoptosis of SCs. Secondly, we investigated the relationship between TPI1 and miR-1285-3p, and whether miR-1285-3p regulates the proliferation and apoptosis of SCs, and participates in glycolysis by targeting TPI1. Results showed that overexpression of TPI1 increased the proliferation rate and decreased apoptosis of SCs. In addition, overexpression of TPI1 altered glycolysis and metabolism signaling pathways and significantly increased the amount of the final product lactic acid. Further analysis showed that miR-1285-3p inhibited TPI1 by directly targeting its 3'untranslated region. Overexpression of miR-1285-3p suppressed the proliferation of SCs, and this effect was partially reversed by restoration of TPI1 expression. In summary, this study shows that the miR-1285-3p/TPI1 axis regulates glycolysis in SCs. These findings add to our understanding of the regulation of spermatogenesis in sheep and other mammals.

opencc-by-4.0Jun 2019View details →

Genomic Alterations of the Metabolic Pathways Across 32 Cancer Types and Their Clinical Significance

Supplementary Information for the thesis chapter: Genomic Alterations of the Metabolic Pathways Across 32 Cancer Types and Their Clinical Significance

opencc-by-4.0Dec 2025View details →

Relative abundance tables for bacterial species, pathways, ARGs, and VFGs in "Gut Microbial Community Structure, Metabolic Signature, and Resistome in Dyslipidemia: Insights from Metagenomic Sequencing"

Dyslipidemia, characterized by abnormal blood lipid levels, is a significant risk factor for cardiovascular disease. Emerging evidence suggests that the gut microbiota plays a role in lipid metabolism, although findings across studies have varied. In this study, we analyzed the gut microbiota, metabolic pathways, predicted gut metabolites, and resistome in 1384 participants (895 with dyslipidemia cases and 489 controls) using shotgun metagenomic sequencing. Our results revealed that Bacteroides caccae was enriched in dyslipidemia cases, potentially contributing to inflammation and altered lipid metabolism, while Coprococcus eutactus and Coprococcus catus, known producers of short-chain fatty acids (SCFAs) in lipid regulation, and Blautia obeum, known to be positively impacted by SCFAs, were more abundant in controls. We also identified an enrichment of the dTDP-beta-D-fucofuranose biosynthesis pathway gene family, which is linked to bacterial pathogenicity, in dyslipidemia cases, with Bacteroides stercoris contributing strongly. Dyslipidemia cases exhibited depleted glycogen and peptidoglycan biosynthesis pathways, potentially impairing energy storage and immune function, alongside distinct metabolic profiles, including decreased pseudouridine, which may affect RNA metabolism. Furthermore, we observed a higher abundance of antibiotic-resistance genes, particularly tetQ, in dyslipidemia cases, suggesting a link between gut resistome and metabolic disorders. These findings provide new insights into how dysbiosis of the gut microbiota may contribute to the pathophysiology of dyslipidemia, offering potential avenues for microbiome-based interventions in personalized medicine.

opencc-by-4.0Sep 2024View details →

Time series transcriptomes resolve metabolic pathways underlying crocin's anti-cancer activity: Control FASTQ sequencing reads

Natural products like saffron show promise in treating hepatocellular carcinoma (HCC), but their mechanisms remain unclear. Here, we used time-series transcriptomics to elucidate crocin's anti-cancer mechanisms in HCC cells. We treated HepG2 cells with 1 and 2 mM crocin for 2, 6, 12, and 24 hours and analyzed transcriptomic profiles at each timepoint. The strongest transcriptional response occurred at 2 hours with 1 mM crocin, with diminishing effects at later timepoints. We observed upregulation of metabolic-, adhesion-, and endocytosis-related genes across all timepoints. Pathway analysis revealed activation of DNA damage checkpoints and senescence while proliferation pathways were suppressed. Notably, 52 genes involved in non-alcoholic fatty liver disease were downregulated at 24 hours (FDR p = 8 × 10⁻⁸), suggesting reversal of carcinogenic pathways. Strikingly, crocin consistently downregulated spliceosomal machinery genes across all timepoints while upregulating senescence and autophagy pathways. This spliceosome targeting represents a clinically relevant mechanism, as aberrant splicing drives oncogenesis in more than 90% of cancers. The transcription factor PAX5 was significantly upregulated while oncogenic ELK1 targets were downregulated. Our findings show that crocin treatment is accompanied by HCC cell senescence induction through coordinated spliceosome disruption and metabolic reprogramming, providing novel therapeutic targets for hepatocellular carcinoma. Keywords: Hepatocellular carcinoma (HCC), crocin, transcriptomics, spliceosome, senescence, natural anti-cancer compounds

opencc-zeroApr 2020View details →

Data from: Genomic regions underlying metabolic and neuronal signaling pathways are temporally consistent outliers in a moving avian hybrid zone

The study of hybrid zones can provide insight into the genetic basis of species differences that are relevant for the maintenance of reproductive isolation. Hybrid zones can also provide insight into climate change, species distributions, and evolution. The hybrid zone between black-capped chickadees (Poecile atricapillus) and Carolina chickadees (P. carolinensis) is shifting northward in response to increasing winter temperatures but is not increasing in width. This pattern indicates strong selection against chickadees with admixed genomes. Using high-resolution genomic data, we identified regions of the genomes that are outliers in both time points and do not introgress between the species; these regions may be involved in the maintenance of reproductive isolation. Genes involved in metabolic regulation processes were overrepresented in this dataset. Several gene ontology categories were also temporally consistent—including glutamate signaling, synaptic transmission, and catabolic processes—but the nucleotide variants leading to this pattern were not. Our results support recent findings that hybrids between black-capped and Carolina chickadees have higher basal metabolic rates than either parental species and suffer spatial memory and problem-solving deficits. Metabolic breakdown, as well as spatial memory and problem-solving, in hybrid chickadees may act as strong postzygotic isolation mechanisms in this moving hybrid zone.

Fig. 5 in L-DOPA synthesis in Mucuna pruriens (L.) DC. is regulated by polyphenol oxidase and not CYP 450/tyrosine hydroxylase: An analysis of metabolic pathway using biochemical and molecular markers

Fig. 5. The amplicons generated using degenerate primer approach. (a) Lane M-DNA ladder, Lane 1–250 bp amplicon generated using MTH –F and MTH-R primer pairs of TH gene (b) Lane M-DNA ladder, Lane 1 and 2–800 bp amplicon using primers deduced from the peptide sequence derived through LCMS/MS.

Fig. 4 in L-DOPA synthesis in Mucuna pruriens (L.) DC. is regulated by polyphenol oxidase and not CYP 450/tyrosine hydroxylase: An analysis of metabolic pathway using biochemical and molecular markers

Fig. 4. Effect of enzyme inhibitors on L-DOPA production in callus cultures of M. pruriens was estimated using HPTLC. The culture without inhibitor was treated as negative control and cultures with different concentration of the inhibitor were the test samples. (Control-untreated, C = Cimetidine at 1.98 μM and 19.8 μM; Q = Quinidine at 1.46 μM and 14.6 μM; A = L-ascorbic acid at 567 μM and 851 μM; K = Kojic acid at 703 μM and 1055 μM).

Fig. 3 in L-DOPA synthesis in Mucuna pruriens (L.) DC. is regulated by polyphenol oxidase and not CYP 450/tyrosine hydroxylase: An analysis of metabolic pathway using biochemical and molecular markers

Fig. 3. Effect of substrate concentration on partially purified enzymes. The assay was performed for PPO activity with 50 mM catechol as substrate at pH 6.0 while keeping the temperature for reaction at 30 ◦ C. For TH activity, 30 mM L-tyrosine was the substrate and assay done at pH 7.0 and 25 ◦ C.

Fig. 2 in L-DOPA synthesis in Mucuna pruriens (L.) DC. is regulated by polyphenol oxidase and not CYP 450/tyrosine hydroxylase: An analysis of metabolic pathway using biochemical and molecular markers

Fig. 2. Effect of pH on the activity of partially purified enzymes from Mucuna pruriens. The assay was performed using 50 mM catechol and 30 mM L-tyrosine as substrates for the PPO and TH enzyme activity, respectively. Four different buffers with their optimal buffering capacity in the pH range of 3–10 were used in separate assays.

Fig. 7 in L-DOPA synthesis in Mucuna pruriens (L.) DC. is regulated by polyphenol oxidase and not CYP 450/tyrosine hydroxylase: An analysis of metabolic pathway using biochemical and molecular markers

Fig. 7. Homology modelling and secondary structure prediction of PPO enzyme from Mucuna pruriens (a) Predicted secondary structure of PPO (b) Phyre2 protein model for PPO with 3D model dimensions (in Å) (X:49.941 Y:64.463 Z:57.979). Image colored by rainbow N → C terminus (c) Three dimensional SWISS protein model for PPO enzyme with two active copper binding ligands (copper ions bridging oxygen moiety is illustrated as small yellow spheres highlighted in the box), conserved histidine residues and metal complex interactions (in dotted lines). Chain A for Ligand 1: H.183, H.204, H.213, F.367, H.371; metal interactions: A:H.183, A:H.204, A:H.213. Chain A for Ligand 2: H.337, H.341, F.367, H.370, H.371; metal interactions: A:H.337, A:H.341, A:H.371). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 6. The 1800 in L-DOPA synthesis in Mucuna pruriens (L.) DC. is regulated by polyphenol oxidase and not CYP 450/tyrosine hydroxylase: An analysis of metabolic pathway using biochemical and molecular markers

Fig. 6. The 1800 bp amplicon of full-length PPO cDNA obtained after deducing the 5′and 3′ ends through RACE analysis. Lane 1- 1 Kb DNA marker, Lane 2 and 3 the amplicon in duplicate after amplification using gene specific primers.

closedIPD-NOFeb 2026View details →

ET1 Concentration, Metabolic Pathway Activation, and Pulmonary Blood Flow in Infants Undergoing Superior Cavo-Pulmonary Anastomosis

ClinicalTrials.gov study NCT03404258. IPD Sharing: NO. Countries: 1. Publications: 1.

restrictedIPD-UNDECIDEDFeb 2026View details →

The Impact of Pectin Supplementation on Systematic Inflammation Pathway, Gut Microbiome, and Metabolic Health in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

ClinicalTrials.gov study NCT07093346. IPD Sharing: UNDECIDED. Countries: 1. Publications: 0.

restrictedIPD-UNDECIDEDFeb 2026View details →

Dietary Modulation of Gene Expression and Metabolic Pathways in Glucose Metabolism

ClinicalTrials.gov study NCT00573781. IPD Sharing: Not stated. Countries: 1. Publications: 7.

controlledIPD-YESFeb 2026View details →

Pilot Study To Investigate Targetable Metabolic Pathways Sustaining Triple Negative Breast Cancer

ClinicalTrials.gov study NCT03457779. IPD Sharing: YES. Countries: 1. Publications: 1.