16 research outputs found
Untargeted Metabolomic Plasma Profiling of Emirati Dialysis Patients with Diabetes versus Non-Diabetic: A Pilot Study
No full textDiabetic kidney disease (DKD) is a severe irreversible complication of diabetes mellitus that further disturbs glucose metabolism. Identifying metabolic changes in the blood may provide early insight into DKD pathogenesis. This study aims to determine blood biomarkers differentiating DKD from non-diabetic kidney disease in the Emirati population utilizing the LC-MS/MS platform. Blood samples were collected from hemodialysis subjects with and without diabetes to detect indicators of pathological changes using an untargeted metabolomics approach. Metabolic profiles were analyzed based on clinically confirmed diabetic status and current HbA1c values. Five differentially significant metabolites were identified based on the clinically confirmed diabetic status, including hydroxyprogesterone and 3,4-Dihydroxymandelic acid. Similarly, we identified seven metabolites with apparent differences between Dialysis Diabetic (DD) and Dialysis non-Diabetic (DND) groups, including isovalerylglycine based on HbA1c values. Likewise, the top three metabolic pathways, including Tyrosine metabolism, were identified following the clinically confirmed diabetic status. As a result, nine different metabolites were enriched in the identified metabolic pathways, such as 3,4-Dihydroxymandelic acid. As a result, eleven different metabolites were enriched, including Glycerol. This study provides an insight into blood metabolic changes related to DKD that may lead to more effective management strategies
Mass spectrometric analysis of bioactive conditioned media of bacteria isolated from reptilian gut: supplementary table
No full textAim: To determine whether selected gut bacteria of crocodile exhibit antibacterial properties. Materials &
methods: Two bacteria isolated from Crocodylus porosus gut were used, namely: Pseudomonas aeruginosa
and Aeromonas dhakensis. Conditioned media were tested against pathogenic bacteria and metabolites
were analyzed using liquid chromatography-mass spectrometry. Results & conclusion: Antibacterial
assays revealed that conditioned media showed potent effects against pathogenic Gram-positive
and Gram-negative bacteria. LC–MS revealed identity of 210 metabolites. The abundant metabolites
were, N-Acetyl-L-tyrosine, Acetaminophen, Trans-Ferulic acid, N, N-Dimethylformamide, Pyrocatechol,
Cyclohexanone, Diphenhydramine, Melatonin, Gamma–terpinene, Cysteamine, 3-phenoxypropionic acid,
Indole-3-carbinol, Benzaldehyde, Benzocaine, 2-Aminobenzoic acid, 3-Methylindole. These findings
suggest that crocodile gut bacteria are potential source of novel bioactive molecules that can be utilized
as pre/post/antibiotics for the benefit of human health.</p
Mass spectrometric analysis of bioactive conditioned media of bacteria isolated from reptilian gut
No full textAim: To determine whether selected gut bacteria of crocodile exhibit antibacterial properties. Materials & methods: Two bacteria isolated from Crocodylus porosus gut were used, namely: Pseudomonas aeruginosa and Aeromonas dhakensis. Conditioned media were tested against pathogenic bacteria and metabolites were analyzed using liquid chromatography-mass spectrometry. Results & conclusion: Antibacterial assays revealed that conditioned media showed potent effects against pathogenic Gram-positive and Gram-negative bacteria. LC–MS revealed identity of 210 metabolites. The abundant metabolites were, N-Acetyl-L-tyrosine, Acetaminophen, Trans-Ferulic acid, N, N-Dimethylformamide, Pyrocatechol, Cyclohexanone, Diphenhydramine, Melatonin, Gamma–terpinene, Cysteamine, 3-phenoxypropionic acid, Indole-3-carbinol, Benzaldehyde, Benzocaine, 2-Aminobenzoic acid, 3-Methylindole. These findings suggest that crocodile gut bacteria are potential source of novel bioactive molecules that can be utilized as pre/post/antibiotics for the benefit of human health
Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study
No full textAbstract Background Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. Methods This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was d-glutamine and d-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3′,5′-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). Conclusions Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER
DataSheet_1_Exploring the effect of estrogen on Candida albicans hyphal cell wall glycans and ergosterol synthesis.docx
No full textIncreased levels of 17-β estradiol (E2) due to pregnancy in young women or to hormonal replacement therapy in postmenopausal women have long been associated with an increased risk of yeast infections. Nevertheless, the effect underlying the role of E2 in Candida albicans infections is not well understood. To address this issue, functional, transcriptomic, and metabolomic analyses were performed on C. albicans cells subjected to temperature and serum induction in the presence or absence of E2. Increased filament formation was observed in E2 treated cells. Surprisingly, cells treated with a combination of E2 and serum showed decreased filament formation. Furthermore, the transcriptomic analysis revealed that serum and E2 treatment is associated with downregulated expression of genes involved in filamentation, including HWP1, ECE1, IHD1, MEP1, SOD5, and ALS3, in comparison with cells treated with serum or estrogen alone. Moreover, glucose transporter genes HGT20 and GCV2 were downregulated in cells receiving both serum and E2. Functional pathway enrichment analysis of the differentially expressed genes (DEGs) suggested major involvement of E2 signaling in several metabolic pathways and the biosynthesis of secondary metabolites. The metabolomic analysis determined differential secretion of 36 metabolites based on the different treatments’ conditions, including structural carbohydrates and fatty acids important for hyphal cell wall formation such as arabinonic acid, organicsugar acids, oleic acid, octadecanoic acid, 2-keto-D-gluconic acid, palmitic acid, and steriacstearic acid with an intriguing negative correlation between D-turanose and ergosterol under E2 treatment. In conclusion, these findings suggest that E2 signaling impacts the expression of several genes and the secretion of several metabolites that help regulate C. albicans morphogenesis and virulence.</p
Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation
No full textHypoxia-inducible factor-1 (HIF-1) is a key regulator for balancing oxygen in the cells. It is a transcription factor that regulates the expression of target genes involved in oxygen homeostasis in response to hypoxia. Recently, research has demonstrated the multiple roles of HIF-1 in the pathophysiology of various diseases, including cancer. It is a crucial mediator of the hypoxic response and regulator of oxygen metabolism, thus contributing to tumor development and progression. Studies showed that the expression of the HIF-1α subunit is significantly upregulated in cancer cells and promotes tumor survival by multiple mechanisms. In addition, HIF-1 has potential contributing roles in cancer progression, including cell division, survival, proliferation, angiogenesis, and metastasis. Moreover, HIF-1 has a role in regulating cellular metabolic pathways, particularly the anaerobic metabolism of glucose. Given its significant and potential roles in cancer development and progression, it has been an intriguing therapeutic target for cancer research. Several compounds targeting HIF-1-associated processes are now being used to treat different types of cancer. This review outlines emerging therapeutic strategies that target HIF-1 as well as the relevance and regulation of the HIF-1 pathways in cancer. Moreover, it addresses the employment of nanotechnology in developing these promising strategies
Correction: Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: a multi-omics approach.
No full text[This corrects the article DOI: 10.1371/journal.pone.0259588.]
Transcriptomic changes of <i>C</i>. <i>albicans ppg1</i>Δ<i>/</i>Δ strain growing under strong filament-inducing condition, 10% serum at 37°C.
No full text(A) Scatter plots of DEGs, X and Y axes represent log10 transformed gene expression level, red color represents significantly upregulated genes, and blue color represents significantly down-regulated genes in W.S. and P.S. at the 5 hr. time point. (B) Pathway classification of DEGs. The X-axis represents the number of DEG. Y-axis represents the functional classification of KEGG. There are seven KEGG pathways: Cellular Processes, Environmental Information Processing, Genetic Information Processing, Metabolism, Organismal Systems.</p
