Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation

Oxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial β-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin β-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-γ. Last, dampening oxylipin levels by β-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial β-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.

The Role of Sphingolipids Metabolism in Cancer Drug Resistance

Drug resistance continues to be one of the major challenges to cure cancer. As research in this field evolves, it has been proposed that numerous bioactive molecules might be involved in the resistance of cancer cells to certain chemotherapeutics. One well-known group of lipids that play a major role in drug resistance are the sphingolipids. Sphingolipids are essential components of the lipid raft domains of the plasma membrane and this structural function is important for apoptosis and/or cell proliferation. Dysregulation of sphingolipids, including ceramide, sphingomyelin or sphingosine 1-phosphate, has been linked to drug resistance in different types of cancer, including breast, melanoma or colon cancer. Sphingolipid metabolism is complex, involving several lipid catabolism with the participation of key enzymes such as glucosylceramide synthase (GCS) and sphingosine kinase 1 (SPHK1). With an overview of the latest available data on this topic and its implications in cancer therapy, this review focuses on the main enzymes implicated in sphingolipids metabolism and their intermediate metabolites involved in cancer drug resistance.

Diallyl-n-Sulfide of Garlic Inhibits Glycogenolysis in Heat-Stressed Laying Sentul Chicken

Heat stress causes a decrease in metabolic function and immunity, which results in a decrease in production. The provision of natural extracts such as the active compound dyally n-suldifa (Dn-S) is one strategy to overcome the adverse effects of heat stress. One hundred and twenty-five female laying native chickens, with an average body weight of 1213.83±15.52 g, 40 weeks old, were used in this experiment, to study the impact of Dn-S administration from garlic on the metabolite profile of the glycogenolysis pathway. laying. Laying hens were distributed into five treatment groups, each with 25 samples. Dn-S isolation from garlic isolated by distillation technique. The study was carried out with five types of experimental treatments, as follows the group with a comfort zone temperature (24°C) and without the administration of Diallyl n-Sulfide (Dn-S), heat stress (38°C) and without Dn-S, heat stress (38°C) and 100 µL Dn-S, heat stress (38°C) and 125 µL Dn-S, heat stress (38°C) and 150 µL Dn-S/head. Based on the results of the study, it was shown that heat stress causes an increase in the rate of glycogenolysis and intermediate metabolites and their catalyzing enzymes. It appears that the administration of 150 µL Dn-S, effectively reduces the rate of glycogenolysis. It was concluded that heat stress on laying hens could be avoid by administering garlic Dn-S.

The Flavonoid Biosynthesis Network in Plants

Flavonoids are an important class of secondary metabolites widely found in plants, contributing to plant growth and development and having prominent applications in food and medicine. The biosynthesis of flavonoids has long been the focus of intense research in plant biology. Flavonoids are derived from the phenylpropanoid metabolic pathway, and have a basic structure that comprises a C15 benzene ring structure of C6-C3-C6. Over recent decades, a considerable number of studies have been directed at elucidating the mechanisms involved in flavonoid biosynthesis in plants. In this review, we systematically summarize the flavonoid biosynthetic pathway. We further assemble an exhaustive map of flavonoid biosynthesis in plants comprising eight branches (stilbene, aurone, flavone, isoflavone, flavonol, phlobaphene, proanthocyanidin, and anthocyanin biosynthesis) and four important intermediate metabolites (chalcone, flavanone, dihydroflavonol, and leucoanthocyanidin). This review affords a comprehensive overview of the current knowledge regarding flavonoid biosynthesis, and provides the theoretical basis for further elucidating the pathways involved in the biosynthesis of flavonoids, which will aid in better understanding their functions and potential uses.

Synergistic PAHs biodegradation by a mixed bacterial community: Based on a multisubstrate enrichment approach

Polycyclic aromatic hydrocarbons (PAHs) are highly hard-biodegradable compounds. Therefore, in this work, a multisubstrate enrichment approach was proposed to develop a bacterial community named MBF from activated sludge of coking wastewater plant capable of degrading mixed-PAHs consisting of phenanthrene and pyrene (50 mg/L of each) by 98.8% and 73.3% within 5 days, respectively. The bacterial community could maintain its degradation ability to mixed PAHs relatively under temperatures (20°C–35°C), pH values (5.0–9.0), and salinities (0–10 g/L NaCl). Additionally, the bacterial community MBF degraded 58.9%, 79.9%, and 80.7% of mixed PAHs in the presence of catechol, salicylic acid, and phthalic acid, respectively within 5 days. High-throughput sequencing of 16S rRNA gene amplicon analysis showed that the bacterial community MBF was dominated by Pseudomonas in most treatments, and Burkholderia was predominant under both acidic condition and high salt concentrations. Furthermore, the composition of microbial communities of the bacterial community was significantly different with/without addition of pathway intermediate metabolites after biodegradation of mixed PAHs, revealing the metabolic burden may be distributed between members of this bacterial community. Those results demonstrate that the biodegradation ability of MBF could be maintained with the bacterial community structure altering when facing environmental variations or changes in composition of target contaminants.

Systematic identification of molecular mediators underlying sensing of Staphylococcus aureus by Pseudomonas aeruginosa

Bacteria typically exist in dynamic, multispecies communities where polymicrobial interactions influence fitness. Elucidating the molecular mechanisms underlying these interactions is critical for understanding and modulating bacterial behavior in natural environments. While bacterial responses to foreign species are frequently characterized at the molecular and phenotypic level, the exogenous molecules that elicit these responses are understudied. Here we outline a systematic strategy based on transcriptomics combined with genetic and biochemical screens of promoter-reporters to identify the molecules from one species that are sensed by another. We utilized this method to study interactions between the pathogens Pseudomonas aeruginosa and Staphylococcus aureus that are frequently found in co-infections. We discovered that P. aeruginosa senses diverse staphylococcal exoproducts including the metallophore staphylopine, intermediate metabolites citrate and acetoin, and multiple molecules that modulate its iron starvation response. Further, we show that staphylopine inhibits biofilm formation and that P. aeruginosa can utilize citrate and acetoin for growth, revealing that these interactions have both antagonistic and beneficial effects. Our screening approach thus identified multiple S. aureus secreted molecules that are sensed by P. aeruginosa and affect its physiology, demonstrating the efficacy of this approach, and yielding new insight into the molecular basis of interactions between these two species.

Detection of auxinic compounds in germinating seedlings

Tryptophan (TRP) is a metabolite from which several important metabolic syntheses arise in plants, animals, and humans. In bacteria and fungi, it is a precursor of Indole Acetic acid (IAA) using various metabolic pathways. The objective of this study is the detection of intermediate metabolites in the synthesis of IAA in seeds of several species in the germination process. In the study, seeds of plant species grown in deionized water were placed in order to stimulate germination and samples were taken every 24 hours. High performance liquid chromatography (HPLC) was used for the detection of the compounds. The results show that the pH of the medium is altered and there is no pattern of behavior. Regarding the detected compounds, in addition to TRP, there is indole-3-acetamide (IAM), 3-indoleacetonitrile (IAN), tryptamine (TRM), which are part of the TRP-dependent routes, since they use this amino acid as a precursor. Anthranilic acid (AA) and kynurenine (KYN), which are part of the Independent TRP pathway, were also detected. IAA and TRP were also detected during the germination process of the studied seeds (Sorghum bicolor, T aesativum, Zea mayz, Phaseolus vulgaris, G. hirsutum, Cucurbita maxima). Finally, it was observed that the seeds, due to weight loss, suffer physical wear during the germination process, since there is a difference between the initial dry weight and the weight of the seeds at the end of the study.

Role of Mitochondria in Neurodegenerative Diseases: From an Epigenetic Perspective

Mitochondria, the centers of energy metabolism, have been shown to participate in epigenetic regulation of neurodegenerative diseases. Epigenetic modification of nuclear genes encoding mitochondrial proteins has an impact on mitochondria homeostasis, including mitochondrial biogenesis, and quality, which plays role in the pathogenesis of neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. On the other hand, intermediate metabolites regulated by mitochondria such as acetyl-CoA and NAD+, in turn, may regulate nuclear epigenome as the substrate for acetylation and a cofactor of deacetylation, respectively. Thus, mitochondria are involved in epigenetic regulation through bidirectional communication between mitochondria and nuclear, which may provide a new strategy for neurodegenerative diseases treatment. In addition, emerging evidence has suggested that the abnormal modification of mitochondria DNA contributes to disease development through mitochondria dysfunction. In this review, we provide an overview of how mitochondria are involved in epigenetic regulation and discuss the mechanisms of mitochondria in regulation of neurodegenerative diseases from epigenetic perspective.