PubMed

Metabolites. 2023 Feb 14;13(2):277. doi: 10.3390/metabo13020277.ABSTRACTIn this study, a beetroot peel flour was made, and its in vitro antioxidant activity was determined in aqueous (BPFw) and ethanolic (BPFe) extracts. The influence of BPFw on breast cancer cell viability was also determined. A targeted betalain profile was obtained using high-resolution Q-Extractive Plus Orbitrap mass spectrometry (Obrtitrap-HRMS) alongside untargeted chemical profiling of BPFw using Ultra-High-Performance Liquid Chromatography with High-Resolution Mass Spectrometry (UHPLC-HRMS). BPFw and BPFe presented satisfactory antioxidant activities, with emphasis on the total phenolic compounds and ORAC results for BPFw (301.64 ± 0.20 mg GAE/100 g and 3032.78 ± 55.00 µmol T/100 g, respectively). The MCF-7 and MDA-MB-231 breast cancer cells presented reductions in viability when treated with BPFw, showing dose-dependent behavior, with MDA-MB-231 also showing time-dependent behavior. The chemical profiling of BPFw led to the identification of 9 betalains and 59 other compounds distributed amongst 28 chemical classes, with flavonoids and their derivates and coumarins being the most abundant. Three forms of betalain generated via thermal degradation were identified. However, regardless of thermal processing, the BPF still presented satisfactory antioxidant and anticancer activities, possibly due to synergism with other identified molecules with reported anticancer activities via different metabolic pathways.PMID:36837895 | DOI:10.3390/metabo13020277

Metabolites. 2023 Feb 14;13(2):275. doi: 10.3390/metabo13020275.ABSTRACTPistacia lentiscus L. is a medicinal plant that grows spontaneously throughout the Mediterranean basin and is traditionally used to treat diseases, including diabetes. The aim of this work consists of the evaluation of the α-glucosidase inhibitory effect (i.e., antidiabetic activity in vitro) of different extracts from the leaves, stem barks and fruits of P. lentiscus harvested on mountains and the littoral of Tizi-Ouzou in Algeria. Metabolomic profiling combined with a chemometric approach highlighted the variation of the antidiabetic properties of P. lentiscus according to the plant's part and origin. A multiblock OPLS analysis showed that the metabolites most involved in α-glucosidase inhibition activity were mainly found in the stem bark extracts. The highest inhibitory activity was found for the stem bark extracts, with averaged inhibition percentage values of 84.7% and 69.9% for the harvested samples from the littoral and mountain, respectively. On the other hand, the fruit extracts showed a lower effect (13.6%) at both locations. The UHPLC-ESI-HRMS characterization of the metabolites most likely responsible for the α-glucosidase-inhibitory activity allowed the identification of six compounds: epigallocatechin(4a>8)epigallocatechin (two isomers), (epi)gallocatechin-3'-O-galloyl-(epi)gallocatechin (two isomers), 3,5-O-digalloylquinic acid and dihydroxy benzoic acid pentoside.PMID:36837894 | DOI:10.3390/metabo13020275

Metabolites. 2023 Feb 14;13(2):271. doi: 10.3390/metabo13020271.ABSTRACTThe gut-liver axis has been recognized as a potential pathway in which dietary factors may contribute to liver disease in people living with HIV (PLWH). The objective of this study was to explore associations between dietary quality, the fecal microbiome, the metabolome, and liver health in PLWH from the Miami Adult Studies on HIV (MASH) cohort. We performed a cross-sectional analysis of 50 PLWH from the MASH cohort and utilized the USDA Healthy Eating Index (HEI)-2015 to measure diet quality. A Fibrosis-4 Index (FIB-4) score < 1.45 was used as a strong indication that advanced liver fibrosis was not present. Stool samples and fasting blood plasma samples were collected. Bacterial composition was characterized using 16S rRNA sequencing. Metabolomics in plasma were determined using gas and liquid chromatography/mass spectrometry. Statistical analyses included biomarker identification using linear discriminant analysis effect size. Compared to participants with FIB-4 ≥ 1.45, participants with FIB-4 < 1.45 had higher intake of dairy (p = 0.006). Fibrosis-4 Index score was inversely correlated with seafood and plant protein HEI component score (r = -0.320, p = 0.022). The relative abundances of butyrate-producing taxa Ruminococcaceae, Roseburia, and Lachnospiraceae were higher in participants with FIB-4 < 1.45. Participants with FIB-4 < 1.45 also had higher levels of caffeine (p = 0.045) and related metabolites such as trigonelline (p = 0.008) and 1-methylurate (p = 0.023). Dietary components appear to be associated with the fecal microbiome and metabolome, and liver health in PLWH. Future studies should investigate whether targeting specific dietary components may reduce liver-related morbidity and mortality in PLWH.PMID:36837890 | DOI:10.3390/metabo13020271

Metabolites. 2023 Feb 13;13(2):268. doi: 10.3390/metabo13020268.ABSTRACTCadmium (Cd) is a toxic heavy metal, which will lead to ecosystem contamination, threatening the life of grazing animals. Goats are an important grazing animal biomarker to evaluate Cd toxicity, but the effect of short-term and high-concentration Cd toxicity on goat liver function and its latent mechanism is still unclear. A total of ten male Guizhou black goats were randomly divided into two groups: CON group, sterilized tap water (no CdCl2), and Cd group (20 mg Cd·kg-1·BW, CdCl2⋅2.5H2O). The test lasted for 30 days. In this study, we found that Cd poisoning in drinking water affected significantly the distribution of Cd in the goat offal and tissues, and damaged the goat's immune function of the liver. With a metabolomics approach, 59 metabolites were identified. Metabolomics analysis suggested that Cd affected lipid and amino acid metabolism of the goat liver. Collectively, our results confirmed the effect of Cd on liver function and liver metabolism, and provided insights on the molecular basis for early warnings of Cd poisoning in goats.PMID:36837887 | DOI:10.3390/metabo13020268

Metabolites. 2023 Feb 13;13(2):267. doi: 10.3390/metabo13020267.ABSTRACTBoth genetic and non-genetic factors are important in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to identify novel metabolites and pathways associated with NAFLD by including both genetic and non-genetic factors in statistical analyses. We genotyped six genetic variants in the PNPLA3, TM6SF2, MBOAT7, GCKR, PPP1R3B, and HSD17B13 genes reported to be associated with NAFLD. Non-targeted metabolomic profiling was performed from plasma samples. We applied a previously validated fatty liver index to identify participants with NAFLD. First, we associated the six genetic variants with 1098 metabolites in 2 339 men without NAFLD to determine the effects of the genetic variants on metabolites, and then in 2 535 men with NAFLD to determine the joint effects of genetic variants and non-genetic factors on metabolites. We identified several novel metabolites and metabolic pathways, especially for PNPLA3, GCKR, and PPP1R38 variants relevant to the pathophysiology of NAFLD. Importantly, we showed that each genetic variant for NAFLD had a specific metabolite signature. The plasma metabolite signature was unique for each genetic variant, suggesting that several metabolites and different pathways are involved in the risk of NAFLD. The FLI index reliably identifies metabolites for NAFLD in large population-based studies.PMID:36837886 | DOI:10.3390/metabo13020267

Metabolites. 2023 Feb 11;13(2):263. doi: 10.3390/metabo13020263.ABSTRACTThe SARS-CoV-2 virus primarily infects salivary glands suggesting a change in the saliva metabolite profile; this shift may be used as a monitoring instrument during SARS-CoV-2 infection. The present study aims to determine the salivary metabolomic profile of patients with and post-SARS-CoV-19 infection. Patients were without (PCR-), with SARS-CoV-2 (PCR+), or post-SARS-CoV-2 infection. Unstimulated whole saliva was collected, and the 1H spectra were acquired in a 500 MHz Bruker nuclear magnetic resonance spectrometer at 25 °C. They were subjected to multivariate analysis using principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), as well as univariate analysis through t-tests (SPSS 20.0, IL, USA), with a significance level of p < 0.05. A distinction was found when comparing PCR- subjects to those with SARS-CoV-2 infection. When comparing the three groups, the PLS-DA cross-validation presented satisfactory accuracy (ACC = 0.69, R2 = 0.39, Q2 = 0.08). Seventeen metabolites were found in different proportions among the groups. The results suggested the downregulation of major amino acid levels, such as alanine, glutamine, histidine, leucine, lysine, phenylalanine, and proline in the PCR+ group compared to the PCR- ones. In addition, acetate, valerate, and capronic acid were higher in PCR- patients than in PCR+. Sucrose and butyrate were higher in post-SARS-CoV-2 infection compared to PCR-. In general, a reduction in amino acids was observed in subjects with and post-SARS-CoV-2 disease. The salivary metabolomic strategy NMR-based was able to differentiate between non-infected individuals and those with acute and post-SARS-CoV-19 infection.PMID:36837882 | DOI:10.3390/metabo13020263

Metabolites. 2023 Feb 10;13(2):259. doi: 10.3390/metabo13020259.ABSTRACTThis study investigated the effects of maternal nutrition on the plasma metabolome of Nellore bulls in the rearing and finishing phases, and metabolic differences between these phases. For this study, three nutritional approaches were used in 126 cows during pregnancy: NP-(control) mineral supplementation; PP-protein-energy supplementation in the final third; and FP-protein-energy supplementation during the entire pregnancy. We collected blood samples from male offspring in the rearing (450 ± 28 days old) and finishing phases (660 ± 28 days old). The blood was processed, and from plasma samples, we performed the targeted metabolome analysis (AbsoluteIDQ® p180 Kit). Multiple linear regression, principal component analysis (PCA), repeated measures analysis over time, and an enrichment analysis were performed. PCA showed an overlap of treatments and time clusters in the analyses. We identified significant metabolites among the treatments (rearing phase = six metabolites; finishing phase = three metabolites) and over time (21 metabolites). No significant metabolic pathways were found in the finishing phase, however, we found significant pathways in the rearing phase (Arginine biosynthesis and Histidine metabolism). Thus, prenatal nutrition impacted on plasma metabolome of bulls during the rearing and finishing phase and the different production stages showed an effect on the metabolic levels of bulls.PMID:36837878 | DOI:10.3390/metabo13020259

Metabolites. 2023 Feb 10;13(2):258. doi: 10.3390/metabo13020258.ABSTRACTMany unique chemical metabolites with significant antitumor activities have been isolated from Garcinia species and have become a leading hotspot of antitumor research in recent years. The aim of this study was to identify bioactive compounds from different plant parts (leaf, branch, stem bark, fruit, and seed) of G. xanthochymus through combining LC-MS-based metabolomics with cytotoxicity assays. As a result, 70% methanol seed extract exerted significant cytotoxic effects on five human cancer cell types (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480). LC-MS-based metabolomics analysis was used, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), in order to identify 12 potential markers from seed extract that may relate to bioactivity. LC-MS guidance isolated the markers to obtain three compounds and identified new isopentenyl phloroglucinols (1-3, named garxanthochin A-C), using spectroscopic methods. Among them, garxanthochin B (2) demonstrated moderate inhibitory activities against five human cancer cell types, with IC50 values of 14.71~24.43 μM. These findings indicate that G. xanthochymus seed has significant cytotoxic activity against cancer cells and garxanthochin B has potential applications in the development of antitumor-led natural compounds.PMID:36837877 | DOI:10.3390/metabo13020258

Metabolites. 2023 Feb 9;13(2):252. doi: 10.3390/metabo13020252.ABSTRACTThis work focused on the metabolomic profiling of the conditioned medium (FS03CM) produced by an anaerobic bacterium closely related to Terrisporobacter spp. to identify potential antimicrobial metabolites. The metabolome of the conditioned medium was profiled by two-channel Chemical Isotope Labelling (CIL) LC-MS. The detected metabolites were identified or matched by conducting a library search using different confidence levels. Forty-eight significantly changed metabolites were identified with high confidence after the growth of isolate FS03 in cooked meat glucose starch (CMGS) medium. Some of the secondary metabolites identified with known antimicrobial activities were 4-hydroxyphenyllactate, 3-hydroxyphenylacetic acid, acetic acid, isobutyric acid, valeric acid, and tryptamine. Our findings revealed the presence of different secondary metabolites with previously reported antimicrobial activities and suggested the capability of producing antimicrobial metabolites by the anaerobic bacterium FS03.PMID:36837871 | DOI:10.3390/metabo13020252

Metabolites. 2023 Feb 8;13(2):246. doi: 10.3390/metabo13020246.ABSTRACTIn plant biology, metabolomics is often used to quantitatively assess small molecules, metabolites, and their intermediates in plants. Metabolomics has frequently been applied to detect metabolic alterations in plants exposed to various biotic and abiotic stresses, including pesticides. The widespread use of pesticides and agrochemicals in intensive crop production systems is a serious threat to the functionality and sustainability of agroecosystems. Pesticide accumulation in soil may disrupt soil-plant relationships, thereby posing a pollution risk to agricultural output. Application of metabolomic techniques in the assessment of the biological consequences of pesticides at the molecular level has emerged as a crucial technique in exposome investigations. State-of-the-art metabolomic approaches such as GC-MS, LC-MS/MS UHPLC, UPLC-IMS-QToF, GC/EI/MS, MALDI-TOF MS, and 1H-HR-MAS NMR, etc., investigating the harmful effects of agricultural pesticides have been reviewed. This updated review seeks to outline the key uses of metabolomics related to the evaluation of the toxicological impacts of pesticides on agronomically important crops in exposome assays as well as bench-scale studies. Overall, this review describes the potential uses of metabolomics as a method for evaluating the safety of agricultural chemicals for regulatory applications. Additionally, the most recent developments in metabolomic tools applied to pesticide toxicology and also the difficulties in utilizing this approach are discussed.PMID:36837865 | DOI:10.3390/metabo13020246

Metabolites. 2023 Feb 7;13(2):242. doi: 10.3390/metabo13020242.ABSTRACTLimited data are available on the effects of pregnancy on the maternal metabolome. Therefore, the objective of this study was to use metabolomics analysis to determine pathways impacted by pregnancy followed by targeted confirmatory analysis to provide more powerful conclusions about metabolic alterations during pregnancy. Forty-seven pregnant women, 18-50 years of age were included in this study, with each subject serving as their own control. Plasma samples were collected between 25 and 28 weeks gestation and again ≥3 months postpartum for metabolomics analysis utilizing an HILIC/UHPLC/MS/MS assay with confirmatory targeted specific concentration analysis for 10 of the significantly altered amino acids utilizing an LC/MS assay. Principle component analysis (PCA) on metabolomics data clearly separated pregnant and postpartum groups and identified outliers in a preliminary assessment. Of the 980 metabolites recorded, 706 were determined to be significantly different between pregnancy and postpartum. Pathway analysis revealed three significantly impacted pathways, arginine biosynthesis (p = 2 × 10-5 and FDR = 1 × 10-3), valine, leucine, and isoleucine metabolism (p = 2 × 10-5 and FDR = 2 × 10-3), and xanthine metabolism (p = 4 × 10-5 and FDR = 4 × 10-3). Of these we focused analysis on arginine biosynthesis and branched-chain amino acid (BCAA) metabolism due to their clinical importance and interconnected roles in amino acid metabolism. In the confirmational analysis, 7 of 10 metabolites were confirmed as significant and all 10 confirmed the direction of change of concentrations observed in the metabolomics analysis. The data support an alteration in urea nitrogen disposition and amino acid metabolism during pregnancy. These changes could also impact endogenous nitric oxide production and contribute to diseases of pregnancy. This study provides evidence for changes in both the ammonia-urea nitrogen and the BCAA metabolism taking place during pregnancy.PMID:36837861 | DOI:10.3390/metabo13020242

Metabolites. 2023 Feb 5;13(2):236. doi: 10.3390/metabo13020236.ABSTRACTMetabolomics strategies are important tools to get holistic chemical information from a system, but they are scarcely applied to endophytic fungi to understand their chemical profiles of biosynthesized metabolites. Here Penicillium sp. was cultured using One Strain Many Compounds (OSMAC) conditions as a model system to demonstrate how this strategy can help in understanding metabolic profiles and determining bioactive metabolites with the application of metabolomics and statistical analyses, as well as molecular networking. Penicillium sp. was fermented in different culture media and the crude extracts from mycelial biomass (CEm) and broth (CEb) were obtained, evaluated against bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa), and the metabolomic profiles by LC-DAD-MS were obtained and chemometrics statistical analyses were applied. The CEm and CEb extracts presented different chemical profiles and antibacterial activities; the highest activities observed were against S. aureus from CEm (MIC = 16, 64, and 128 µg/mL). The antibacterial properties from the extracts were impacted for culture media from which the strain was fermented. From the Volcano plot analysis, it was possible to determine statistically the most relevant features for the antibacterial activity, which were also confirmed from biplots of PCA as strong features for the bioactive extracts. These compounds included 75 (13-oxoverruculogen isomer), 78 (austalide P acid), 87 (austalide L or W), 88 (helvamide), 92 (viridicatumtoxin A), 96 (austalide P), 101 (dihydroaustalide K), 106 (austalide k), 110 (spirohexaline), and 112 (pre-viridicatumtoxin). Thus, these features included diketopiperazines, meroterpenoids, and polyketides, such as indole alkaloids, austalides, and viridicatumtoxin A, a rare tetracycline.PMID:36837855 | DOI:10.3390/metabo13020236

Int J Radiat Biol. 2023 Feb 24:1-10. doi: 10.1080/09553002.2023.2182001. Online ahead of print.ABSTRACTPURPOSE: The goal of the current study was to identify longitudinal changes in urinary metabolites following IR exposure and to determine potential alleviation of radiation toxicities by administration of recombinant APC formulations.MATERIALS AND METHODS: Female adult WAG/RijCmcr rats were irradiated with 13.0 Gy leg-out partial body X-rays; longitudinally collected urine samples were subject to LC-MS based metabolomic profiling. Sub-cohorts of rats were treated with three variants of recombinant APC namely, rat wildtype (WT) APC, rat 3K3A mutant form of APC, and human WT APC as two bolus injections at 24 and 48 hours post IR.RESULTS: Radiation induced robust changes in the urinary profiles leading to oxidative stress, severe dyslipidemia, and altered biosynthesis of PUFAs, glycerophospholipids, sphingolipids, and steroids. Alterations were observed in multiple metabolic pathways related to energy metabolism, nucleotide biosynthesis and metabolism that were indicative of disrupted mitochondrial function and DNA damage. On the other hand, sub-cohorts of rats that were treated with rat wildtype-APC showed alleviation of radiation toxicities, in part, at the 90-day time point, while rat 3K3A-APC showed partial alleviation of radiation induced metabolic alterations 14 days after irradiation.CONCLUSIONS: Taken together, these results show that augmenting the Protein C pathway and activity via administration of recombinant APC may be an effective approach for mitigation of radiation induced normal tissue toxicity.PMID:36827630 | DOI:10.1080/09553002.2023.2182001

Sci Adv. 2023 Feb 24;9(8):eade7864. doi: 10.1126/sciadv.ade7864. Epub 2023 Feb 24.ABSTRACTThermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms by which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in the inner mitochondrial membrane (IMM), where it dissipates membrane potential independent of adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across the IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance bidirectionally responds to changes in thermogenic burden. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) made mice cold intolerant and insensitive to β3 adrenergic receptor agonist-induced increase in whole-body oxygen consumption. High-resolution respirometry and fluorometry of BAT mitochondria showed that loss of mitochondrial PE specifically lowers UCP1-dependent respiration without compromising electron transfer efficiency or ATP synthesis. These findings were confirmed by a reduction in UCP1 proton current in PE-deficient mitoplasts. Thus, PE performs a previously unknown role as a temperature-responsive rheostat that regulates UCP1-dependent thermogenesis.PMID:36827367 | DOI:10.1126/sciadv.ade7864

PLoS One. 2023 Feb 24;18(2):e0280868. doi: 10.1371/journal.pone.0280868. eCollection 2023.ABSTRACTTriatoma sanguisuga is one of the major vectors of Trypanosoma cruzi in the southeastern US, where it sustains a robust zoonotic parasite transmission cycle and occasional human infections. A better understanding of triatomine development may allow for alternative approaches to insecticide-based vector control. Indeed, the role of the gut microbiota and bacterial endosymbionts in triatomine development and in their vectorial capacity is emerging. We investigated here the differences in microbiota among nymph and adult T. sanguisuga, to shed light on the metabolomic interactions occurring during development. Microbiota composition was assessed by 16s gene amplification and deep sequencing from field-caught adult bugs and their laboratory-raised progeny. Significant differences in microbiota bacterial diversity and composition were observed between nymphs and adults. Laboratory-raised nymphs showed a higher taxonomic diversity, and at least seven families predominated. On the other hand, field-caught adults had a lower bacterial diversity and four families comprised most of the microbiota. These differences in compositions were associated with differences in predicted metabolism, with laboratory-raised nymphs microbiota metabolizing a limited diversity of carbon sources, with potential for resource competition between bacterial families, and the production of lactic acid as a predominant fermentation product. On the other hand, field-caught adult microbiota was predicted to metabolize a broader diversity of carbon sources, with complementarity rather than competition among taxa, and produced a diverse range of products in a more balanced manner. The restricted functionality of laboratory-raised nymph microbiota may be associated with their poor development in captivity, and further understanding of the metabolic interactions at play may lead to alternative vector control strategies targeting triatomine microbiota.PMID:36827319 | DOI:10.1371/journal.pone.0280868

Proc Natl Acad Sci U S A. 2023 Feb 28;120(9):e2123301120. doi: 10.1073/pnas.2123301120. Epub 2023 Feb 24.ABSTRACTDehydrodiconiferyl alcohol glucoside (DCG) is a phenylpropanoid-derived plant metabolite with reported cytokinin-substituting and cell-division-promoting activity. Despite its claimed activity, DCG did not trigger morphological changes in Arabidopsis seedlings nor did it alter transcriptional shifts in cell division and cytokinin-responsive genes. In reinvestigating the bioactivity of DCG in its original setting, the previously described stimulation of tobacco callus formation could not be confirmed. No evidence was found that DCG is actually taken up by plant cells, which could explain the absence of any observable activity in the performed experiments. The DCG content in plant tissue increased when feeding explants with the DCG aglycone dehydrodiconiferyl alcohol, which is readily taken up and converted to DCG by plant cells. Despite the increased DCG content, no activity for this metabolite could be demonstrated. Our results therefore demand a reevaluation of the often-quoted cytokinin-substituting and cell-division-promoting activity that has previously been attributed to this metabolite.PMID:36827261 | DOI:10.1073/pnas.2123301120

Mar Drugs. 2023 Feb 17;21(2):129. doi: 10.3390/md21020129.ABSTRACTThe marine mesopelagic zone extends from water depths of 200 m to 1000 m and is home to a vast number and diversity of species. It is one of the least understood regions of the marine environment with untapped resources of pharmaceutical relevance. The mesopelagic jellyfish Periphylla periphylla is a well-known and widely distributed species in the mesopelagic zone; however, the diversity or the pharmaceutical potential of its cultivable microbiota has not been explored. In this study, we isolated microorganisms associated with the inner and outer umbrella of P. periphylla collected in Irminger Sea by a culture-dependent approach, and profiled their chemical composition and biological activities. Sixteen mostly gram-negative bacterial isolates were selected and subjected to an OSMAC cultivation regime approach using liquid and solid marine broth (MB) and glucose-yeast-malt (GYM) media. Their ethyl acetate (EtOAc) extracts were assessed for cytotoxicity and antimicrobial activity against fish and human pathogens. All, except one extract, displayed diverse levels of antimicrobial activities. Based on low IC50 values, four most bioactive gram-negative strains; Polaribacter sp. SU124, Shewanella sp. SU126, Psychrobacter sp. SU143 and Psychrobacter sp. SU137, were prioritized for an in-depth comparative and untargeted metabolomics analysis using feature-based molecular networking. Various chemical classes such as diketopiperazines, polyhydroxybutyrates (PHBs), bile acids and other lipids were putatively annotated, highlighting the biotechnological potential in P. periphylla-associated microbiota as well as gram-negative bacteria. This is the first study providing an insight into the cultivable bacterial community associated with the mesopelagic jellyfish P. periphylla and, indeed, the first to mine the metabolome and antimicrobial activities of these microorganisms.PMID:36827170 | DOI:10.3390/md21020129

Mar Drugs. 2023 Jan 28;21(2):95. doi: 10.3390/md21020095.ABSTRACTDespite low temperatures, poor nutrient levels and high pressure, microorganisms thrive in deep-sea environments of polar regions. The adaptability to such extreme environments renders deep-sea microorganisms an encouraging source of novel, bioactive secondary metabolites. In this study, we isolated 77 microorganisms collected by a remotely operated vehicle from the seafloor in the Fram Strait, Arctic Ocean (depth of 2454 m). Thirty-two bacteria and six fungal strains that represented the phylogenetic diversity of the isolates were cultured using an One-Strain-Many-Compounds (OSMAC) approach. The crude EtOAc extracts were tested for antimicrobial and anticancer activities. While antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium was common for many isolates, only two bacteria displayed anticancer activity, and two fungi inhibited the pathogenic yeast Candida albicans. Due to bioactivity against C. albicans and rich chemical diversity based on molecular network-based untargeted metabolomics, Aspergillus versicolor PS108-62 was selected for an in-depth chemical investigation. A chemical work-up of the SPE-fractions of its dichloromethane subextract led to the isolation of a new PKS-NRPS hybrid macrolactone, versicolide A (1), a new quinazoline (-)-isoversicomide A (3), as well as three known compounds, burnettramic acid A (2), cyclopenol (4) and cyclopenin (5). Their structures were elucidated by a combination of HRMS, NMR, [α]D, FT-IR spectroscopy and computational approaches. Due to the low amounts obtained, only compounds 2 and 4 could be tested for bioactivity, with 2 inhibiting the growth of C. albicans (IC50 7.2 µg/mL). These findings highlight, on the one hand, the vast potential of the genus Aspergillus to produce novel chemistry, particularly from underexplored ecological niches such as the Arctic deep sea, and on the other, the importance of untargeted metabolomics for selection of marine extracts for downstream chemical investigations.PMID:36827136 | DOI:10.3390/md21020095

Mar Drugs. 2023 Jan 17;21(2):56. doi: 10.3390/md21020056.ABSTRACTAs one of the first families of marine natural products to undergo clinical trials, the didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed as anticancer therapeutics, the recent re-evaluation of these compounds including synthetically derived dehydrodidemnin B or Aplidine, has led to their advancement towards antiviral applications. While conventionally associated with production in colonial tunicates of the family Didemnidae, recent studies have identified their biosynthetic gene clusters from the marine-derived bacteria Tistrella mobilis. While these studies confirm the production of didemnin X/Y, the low titer and general lack of understanding of their biosynthesis in Tistrella currently prevents the development of effective microbial or synthetic biological approaches for their production. To this end, we conducted a survey of known species of Tistrella and report on their ability to produce the didemnin depsipeptides. These data were used to develop conditions to produce didemnin B at titers over 15 mg/L.PMID:36827097 | DOI:10.3390/md21020056

Metabolomics. 2023 Feb 24;19(3):14. doi: 10.1007/s11306-023-01978-z.ABSTRACTINTRODUCTION: In the advanced stage of chronic kidney disease (CKD), electrolytes, fluids, and metabolic wastes including various uremic toxins, accumulate at high concentrations in the patients' blood. Hemodialysis (HD) is the conventional procedure used worldwide to remove metabolic wastes. The creatinine and urea levels have been routinely monitored to estimate kidney function and effectiveness of the HD process. This study, first from in Indian perspective, aimed at the identification and quantification of major uremic toxins in CKD patients on maintenance HD (PRE-HD), and compared with the healthy controls (HC) as well as after HD (POST-HD).OBJECTIVES: The study mainly focused on the identification of major uremic toxins in Indian perspective and the quantitative analysis of indoxyl sulfate and p-cresol sulfate (routinely targeted uremic toxins), and phenyl sulfate, catechol sulfate, and guaiacol sulfate (targeted for the first time), apart from creatinine and urea in PRE-HD, POST-HD, and HC groups.METHODS: Blood samples were collected from 90 HD patients (both PRE-HD and POST-HD), and 74 HCs. The plasma samples were subjected to direct ESI-HRMS and LC/HRMS for untargeted metabolomics and LC-MS/MS for quantitative analysis.RESULTS: Various known uremic toxins, and a few new and unknown peaks were detected in PRE-HD patients. The p-cresol sulfate and indoxyl sulfate were dominant in PRE-HD, the concentrations of phenyl sulfate, catechol sulfate, and guaiacol sulfate were about 50% of that of indoxyl sulfate. Statistical evaluation on the levels of targeted uremic toxins in PRE-HD, POST-HD, and HC groups showed a significant difference among the three groups. The dialytic clearance of indoxyl sulfate and p-cresol sulfate was found to be < 35%, while that of the other three sulfates was 50-58%.CONCLUSION: LC-MS/MS method was developed and validated to evaluate five major uremic toxins in CKD patients on HD. The levels of the targeted uremic toxins could be used to assess kidney function and the effectiveness of HD.PMID:36826619 | DOI:10.1007/s11306-023-01978-z