Characterization of Metabolites of α-mangostin in Bio-samples from SD Rats by UHPLC-Q-Exactive Orbitrap MS

Background: α-mangostin, a typical xanthone, often exists in Garcinia mangostana L. (Clusiaceae). α-mangostin was found to have a wide range of pharmacological properties. However, its specific metabolic route in vivo remains unclear, while these metabolites may accumulate to exert pharmacological effects, too. Objective: This study aimed to clarify the metabolic pathways of α-mangostin after oral administration to the rats. Methods: Here, an UHPLC-Q-Exactive Orbitrap MS was used for the detection of potential metabolites formed in vivo. A new strategy for the identification of unknown metabolites based on typical fragmentation routes was implemented. Results: A total of 42 metabolites were detected, and their structures were tentatively identified in this study. The results showed that major in vivo metabolic pathways of α-mangostin in rats included methylation, demethylation, methoxylation, hydrogenation, dehydrogenation, hydroxylation, dehydroxylation, glucuronidation, and sulfation. Conclusions: This study is significant to expand our knowledge of the in vivo metabolism of α-mangostin and to understand the mechanism of action of α-mangostin in rats in vivo.

Monitoring of seven industrial anaerobic digesters supplied with biochar

Background Recent research articles indicate that direct interspecies electron transfer (DIET) is an alternative metabolic route for methanogenic archaea that improves microbial methane productivity. It has been shown that multiple conductive materials such as biochar can be supplemented to anaerobic digesters to increase the rate of DIET. However, the industrial applicability, as well as the impact of such supplements on taxonomic profiles, has not been sufficiently assessed to date. Results Seven industrial biogas plants were upgraded with a shock charge of 1.8 kg biochar per ton of reactor content and then 1.8 kg per ton were added to the substrate for one year. A joint analysis for all seven systems showed a decreasing trend for the concentration of acetic acid (p < 0.0001), propionic acid (p < 0.0001) and butyric acid (p = 0.0022), which was significant in all cases. Quantification of the cofactor F420 using fluorescence microscopy showed a reduction in methanogenic archaea by up to a power of ten. Methanogenic archaea could grow within the biochar, even if the number of cells was 4 times less than in the surrounding sludge. 16S-rRNA gene amplicon sequencing showed a higher microbial diversity in the biochar particles than in the sludge, as well as an accumulation of secondary fermenters and halotolerant bacteria. Taxonomic profiles indicate microbial electroactivity, and show the frequent occurrence of Methanoculleus, which has not been described in this context before. Conclusions Our results shed light on the interplay between biochar particles and microbial communities in anaerobic digesters. Both the microbial diversity and the absolute frequency of the microorganisms involved were significantly changed between sludge samples and biochar particles. This is particularly important against the background of microbial process monitoring. In addition, it could be shown that biochar is suitable for reducing the content of inhibitory, volatile acids on an industrial scale.

Genetics Variants in the Epoxygenase Pathway of Arachidonic Metabolism Are Associated with Eicosanoids Levels and the Risk of Diabetic Nephropathy

Genes in the epoxygenase pathway of arachidonic acid metabolism leading to vasoactive eicosanoids, mainly 20-hydroxyeicosatetraenoic (20-HETE) and epoxyeicosatrienoic (EETs) acids, have been related to glucose-induced renal damage in preclinical reports. We genotyped 1088 diabetic kidney disease (DKD) patients and controls for seven polymorphisms in five genes (CYP2C8, CYP2J2, CYP4F2, CYP4A11, and EPHX2) along this metabolic route and evaluated their effect on DKD risk, clinical outcomes, and the plasma/urine levels of eicosanoids measured by LC/MS/MS and immunoenzymatic assays. The CYP4F2 433M variant allele was associated with lower incidence of DKD (OR = 0.65 (0.48–0.90), p = 0.008), whilst the CYP2C8*3/*3 genotype was related to increased risk (OR = 3.21 (1.05–9.87), p = 0.036). Patients carrying the 433M allele also showed lower eGFR [median and interquartile range vs. wildtype carriers: 30.8 (19.8) and 33.0 (23.2) mL/min/1.73 m2, p = 0.037). Finally, the 433VM/MM variant genotypes were associated with lower urinary levels of 20-HETE compared with 433VV (3.14 (0.86) vs. 8.45 (3.69) ng/mg Creatinine, p = 0.024). Our results indicate that the CYP4F2 V433M polymorphism, by decreasing 20-HETE levels, may play an important role in DKD.

Enhanced glyoxylate shunt for efficient production of C4 derivatives using fatty acids feedstocks

Biosynthesis of TCA cycle-derived C4 chemicals through glyoxylate shunt is an attractive metabolic route because it can be drived by TCA-glyoxylate cycle force under aerobic conditions. However, yield of this route is low with at least 1/3 carbon loss from glucose. FAs could sufficiently provide acetyl-CoA by β-oxidation without carbon loss and directly enter the TCA-glyoxylate cycle, which is acknowledged as a promising alternative feedstock. Here β-alanine was selected as the target TCA cycle-derived chemical, of which the theoretical yield is 1.391 g/g FAs, much higher than that of glucose(0.49 g/g). By adopting multi-metabolic engineering strategies and relieving the active oxygen damage caused by FAs utilization, β-alanine production reached 78.05 g/L with a yield of 1.2 g/g, about 86% of theoretical yield. Our study establish a promising bioproduction route of β-alanine from waste FAs (such as gutter oil, palm fatty acid distillate etc.), and more importantly, provide an efficient platform for TCA cycle-derived C4 chemicals biosynthesis.

ExoPhot: a new approach for the study of photosynthesis viability in exoplanetary systems.

&lt;p&gt;NASA and ESA are making plans for the next generation of space telescopes, which should be able to detect biomarkers in the atmospheres of exoplanets in the classical habitable zones around their stars (i.e., the range of separations at which water would be in liquid state on the exoplanet surface). The launch of &lt;em&gt;James Space Webb Telescope&lt;/em&gt; is scheduled for October 2021. The main questions are related with the type of organisms producing such possible biomarkers and with the related metabolism? Will autotrophs be the base of the exoplanet ecological pyramid, as on Earth? Will they be phototroph or chemotroph? Will they be photosynthetic? Oxygenic or anoxygenic? Which will their photosynthetic pigments be? ESA&amp;#8217;s &lt;em&gt;LIFE&lt;/em&gt; or any other new concept for which scientific requirements have not been defined yet might be able to not only detect biomarkers, but to shed light on the actual biochemistry of exoplanet ecosystems. Therefore, investigating the potential variety of photosynthetic systems in exoplanets, either real or to be discovered, is actually very timely, as the requirements of new such telescope concepts are not set yet.&lt;/p&gt; &lt;p&gt;The conversion of solar energy to chemical energy through photosynthesis is considered one of the first metabolic routes on planet Earth. Although a low percentage of the solar radiation from our Sun is captured by photosynthesis, this metabolic route provides the energy to drive all the life on Earth. Cyanobacteria are thought to be the first photosynthetic microorganisms on Earth. Subsequent photosynthetic organisms acquired photosynthesis via cyanobacteria endosymbionts, that evolved into chloroplasts in plants (Tomioka &amp; Sugiura 1983).&lt;/p&gt; &lt;p&gt;At the same time, photosynthesis modified the atmosphere of the early Earth by producing oxygen as a by-product. The concentration in this gas was increased in the primitive atmosphere, transforming the metabolic possibilities for the rest of organisms and, nowadays, oxygen supports the whole aerobic organisms on the planet. The only requirements that photosynthesis has are the exposure to optical radiation from the corresponding star and the availability of water and carbon dioxide (as a carbon source), making photosynthesis a putative imperative metabolism to be present in any particular radiative planetary system.&lt;/p&gt; &lt;p&gt;To deepen into this idea, ExoPhot aims to study the relation between photosynthetic systems on exoplanets around different types of stars (i.e. stellar spectral types) from an astrobiological and multidisciplinary point of view, by focusing on two aspects:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Assess the photosynthetic fitness of a variety of photopigments (either real or hypothetical) as a function of star, exoplanet and atmospheric scenario.&lt;/li&gt; &lt;li&gt;Delineate a range of stellar, exoplanet and atmospheric parameters for which photosynthetic activity might be feasible.&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;To accomplish these goals, we will use state-of-the-art planetary and stellar models to retrieve the radiation signatures at the planet surface for a wide range of exoplanet, atmosphere and host star parameters, and will carry out a quantification of the overlap (convolution) between those spectra with the absorption spectra of photosynthetic pigments, both terrestrial and hypothetical (our own developments on computer-simulated primordial pigments). Here, at the EPSC2021 conference, we present our preliminary results and future work to be developed.&lt;/p&gt; &lt;p&gt;&amp;#160;&lt;/p&gt; &lt;p&gt;&lt;em&gt;Bibliography:&lt;/em&gt;&lt;/p&gt; &lt;p&gt;Tomioka, N. &amp; Sugiura, M. The complete nucleotide sequence of a 16S ribosomal RNA gene from a blue-green alga, Anacystis nidulans. &lt;em&gt;Molecular and General Genetics, &lt;/em&gt;1983&lt;em&gt;, 191&lt;/em&gt;, 46&amp;#8211;50. https://doi.org/10.1007/BF00330888&lt;/p&gt; &lt;p&gt;&amp;#160;&lt;/p&gt;

Monitoring of seven industrial anaerobic digesters supplied with biochar

Background: Recent research articles indicate that direct interspecies electron transfer (DIET) is an alternative metabolic route for methanogenic archaea that improves microbial methane productivity. It has been shown that multiple conductive materials such as biochar can be supplemented to anaerobic digesters to increase the rate of DIET. However, the industrial applicability, as well as the impact of such supplements on taxonomic profiles, has not been sufficiently assessed to date. Results: Seven industrial anaerobic digesters were supplemented with biochar for one year. A positive effect was observed for the spectrum of organic acids as the concentration of acetic, propionic, and butyric acid decreased significantly. Quantification of the cofactor F420 using fluorescence microscopy showed a reduction in methanogenic archaea. 16S-rRNA gene amplicon sequencing showed a higher microbial diversity within biochar particles as well as an accumulation of secondary fermenters and halotolerant bacteria. Taxonomic profiles indicate microbial electroactivity, and show the frequent occurrence of Methanoculleus , which has not been described in this context before. Conclusions: Our results shed light on the interplay between biochar particles and microbial communities in anaerobic digesters. Both the microbial diversity and the absolute frequency of the microorganisms involved were significantly changed between sludge samples and biochar particles. This is particularly important against the background of microbial process monitoring. In addition, it could be shown that biochar is suitable for reducing the content of inhibitory, volatile acids on an industrial scale.

Warburg’s Ghost—Cancer’s Self-Sustaining Phenotype: The Aberrant Carbon Flux in Cholesterol-Enriched Tumor Mitochondria via Deregulated Cholesterogenesis

Interpreting connections between the multiple networks of cell metabolism is indispensable for understanding how cells maintain homeostasis or transform into the decontrolled proliferation phenotype of cancer. Situated at a critical metabolic intersection, citrate, derived via glycolysis, serves as either a combustible fuel for aerobic mitochondrial bioenergetics or as a continuously replenished cytosolic carbon source for lipid biosynthesis, an essentially anaerobic process. Therein lies the paradox: under what conditions do cells control the metabolic route by which they process citrate? The Warburg effect exposes essentially the same dilemma—why do cancer cells, despite an abundance of oxygen needed for energy-generating mitochondrial respiration with citrate as fuel, avoid catabolizing mitochondrial citrate and instead rely upon accelerated glycolysis to support their energy requirements? This review details the genesis and consequences of the metabolic paradigm of a “truncated” Krebs/TCA cycle. Abundant data are presented for substrate utilization and membrane cholesterol enrichment in tumors that are consistent with criteria of the Warburg effect. From healthy cellular homeostasis to the uncontrolled proliferation of tumors, metabolic alterations center upon the loss of regulation of the cholesterol biosynthetic pathway. Deregulated tumor cholesterogenesis at the HMGR locus, generating enhanced carbon flux through the cholesterol synthesis pathway, is an absolute prerequisite for DNA synthesis and cell division. Therefore, expedited citrate efflux from cholesterol-enriched tumor mitochondria via the CTP/SLC25A1 citrate transporter is fundamental for sustaining the constant demand for cytosolic citrate that fuels the elevated flow of carbons from acetyl-CoA through the deregulated pathway of cholesterol biosynthesis.

Helicobacter and the Potential Role in Neurological Disorders: There Is More Than Helicobacter pylori

Trillions of symbiotic microbial cells colonize our body, of which the larger part is present in the human gut. These microbes play an essential role in our health and a shift in the microbiome is linked to several diseases. Recent studies also suggest a link between changes in gut microbiota and neurological disorders. Gut microbiota can communicate with the brain via several routes, together called the microbiome–gut–brain axis: the neuronal route, the endocrine route, the metabolic route and the immunological route. Helicobacter is a genus of Gram-negative bacteria colonizing the stomach, intestine and liver. Several papers show the role of H. pylori in the development and progression of neurological disorders, while hardly anything is known about other Helicobacter species and the brain. We recently reported a high prevalence of H. suis in patients with Parkinson’s disease and showed an effect of a gastric H. suis infection on the mouse brain homeostasis. Here, we discuss the potential role of H. suis in neurological disorders and how it may affect the brain via the microbiome–gut–brain axis.