PubMed

J Ethnopharmacol. 2023 Jul 26:116949. doi: 10.1016/j.jep.2023.116949. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook. f (TwHF) has been used as a traditional Chinese medicine for the treatment of rheumatoid arthritis and nephritis for hundreds of years.AIM OF THE STUDY: Although the efficacy of TwHF in the treatment of RA is definite, its serious side effects and toxicity have also received close attention from domestic and international researchers, so the clinical application of TwHF has been controversial. Most of the current TwHF toxicity studies have been conducted with animals in normal body states, but ignore the effects in pathological states. In this study, we aimed to find out the material basis and metabolic mechanism of the "toxicity/effectiveness" of TwHF on rat kidneys in different body states by using two-way orthogonal partial least squares (O2PLS) method.MATERIALS AND METHODS: In the present study, TwHF was extracted by reflux extraction method using ethanol as the extraction solvent. Firstly, the effects of TwHF on rat kidneys in different body states were first evaluated by detecting creatinine and urea nitrogen levels and morphological changes in kidney pathology identified the components of TwHF in rats in different body states using UPLC-Q-TOF/MS technique. Serum and urine metabolomics were used to search for biomarkers and metabolic pathways by which TwHF exerts renal injury and protection, and finally, O2PLS correlation analysis was used to correlate the components with renal protective and injury biomarkers.RESULTS: TwHF was found to have a protective effect on the kidney of RA rats and an injurious effect on the kidney of normal rats at a dose of 11.25 g/kg/d. The UPLC-Q-TOF/MS technique was used to identify 34 components in TwHF extracts; 23 components and 57 metabolites were identified in the administered rats. O2PLS screened three substances as both toxic and pharmacodynamic components of TwHF, namely 3,5-dimethoxyphenyl-2-propenl-ol, kaurane-16,19,20-triol, and demethylzeylasteral + O, and found that these three components may exert nephrotoxic effects via the nicotinic acid and nicotinamide metabolic pathways and nephroprotective effects via the tryptophan metabolic pathway.CONCLUSION: In this study, O2PLS analysis was used for the first time to combine biomarkers and components in vivo and found the material basis and metabolic mechanism of nephrotoxicity and efficacy of TwHF, which provided key clues for further study on the biological mechanism of toxicity and efficacy of TwHF.PMID:37506782 | DOI:10.1016/j.jep.2023.116949

EBioMedicine. 2023 Jul 26;94:104729. doi: 10.1016/j.ebiom.2023.104729. Online ahead of print.ABSTRACTBACKGROUND: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology.METHODS: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC. We assessed tryptophan and its degradation products by UPLC-MS/MS. IDO2 activity, its potential consequences, and the involvement of the aryl hydrocarbon receptor (AHR) in IDO2 expression were determined in PBMC from another PASC cohort by immunohistochemistry (IHC) for IDO2, IDO1, AHR, kynurenine metabolites, autophagy, and apoptosis. These PBMC were also analyzed by metabolomics and for mitochondrial functioning by respirometry. IHC was also performed on autopsy brain material from two PASC patients.FINDINGS: IDO2 is expressed and active in PBMC from PASC patients, as well as in brain tissue, long after SARS-CoV-2 infection. This is paralleled by autophagy, and in blood cells by reduced mitochondrial functioning, reduced intracellular levels of amino acids and Krebs cycle-related compounds. IDO2 expression and activity is triggered by SARS-CoV-2-infection, but the severity of SARS-CoV-2-induced pathology appears related to the generated specific kynurenine metabolites. Ex vivo, IDO2 expression and autophagy can be halted by an AHR antagonist.INTERPRETATION: SARS-CoV-2 infection triggers long-lasting IDO2 expression, which can be halted by an AHR antagonist. The specific kynurenine catabolites may relate to SARS-CoV-2-induced symptoms and pathology.FUNDING: None.PMID:37506544 | DOI:10.1016/j.ebiom.2023.104729

Immun Inflamm Dis. 2023 Jul;11(7):e936. doi: 10.1002/iid3.936.ABSTRACTINTRODUCTION: Sjögren's disease (SjD) is a chronic autoimmune disease characterized by the loss of the secretory function of the exocrine glands. At present, drugs that can both correct the immune imbalance and improve exocrine gland function are needed. Meanwhile, vasoactive intestinal peptide (VIP) has been reported as a candidate with anti-inflammatory and immunoregulatory properties for treating autoimmune diseases.METHODS: Nonobese diabetic (NOD) mice and the primary splenic lymphocyte cells (SPLCs) were used to construct the SS model. The therapeutic effects of VIP for SjD by evaluating water consumption, histopathology, T cell subsets, and related cytokines. RT-qPCR and Western blot analysis were used to identify the expression of the PTEN/PI3K/AKT pathway.RESULTS: We found that VIP therapy in NOD mice could increase the expression of PTEN and VIP/VPAC1 receptor, as well as decrease the PI3K/AKT pathway. In vitro, the results showed that the PTEN knockdown decreased the Treg/Th17 ratio and enhanced the phosphorylated PI3K/AKT pathway, which were reversed with VIP treatment.CONCLUSIONS: VIP exerts potential therapeutic action in SjD by upregulating PTEN through the PI3K/AKT pathway and Treg/Th17 cell balance.PMID:37506142 | DOI:10.1002/iid3.936

PLoS One. 2023 Jul 28;18(7):e0289214. doi: 10.1371/journal.pone.0289214. eCollection 2023.ABSTRACTInclusion of additive blends is a common dietary strategy to manage post-weaning diarrhea and performance in piglets. However, there is limited mechanistic data on how these additives improve outcomes during this period. To evaluate the effects of Presan FX (MCOA) on the intestinal microbiota and metabolome, diets with or without 0.2% MCOA were compared. Pigs fed MCOA showed improved whole-body metabolism 7 days post-weaning, with decreased (P < 0.05) creatine, creatinine and β-hydroxybutyrate. Alterations in bile-associated metabolites and cholic acid were also observed at the same time-point (P < 0.05), suggesting MCOA increased bile acid production and secretion. Increased cholic acid was accompanied by increased tryptophan metabolites including indole-3-propionic acid (IPA) in systemic circulation (P = 0.004). An accompanying tendency toward increased Lactobacillus sp. in the small intestine was observed (P = 0.05). Many lactobacilli have bile acid tolerance mechanisms and contribute to production of IPA, suggesting increased bile acid production resulted in increased abundance of lactobacilli capable of tryptophan fermentation. Tryptophan metabolism is associated with the mature pig microbiota and many tryptophan metabolites such as IPA are considered beneficial to gut barrier function. In conclusion, MCOA may help maintain tissue metabolism and aid in microbiota re-assembly through bile acid production and secretion.PMID:37506070 | DOI:10.1371/journal.pone.0289214

Acta Microbiol Immunol Hung. 2023 Jul 28. doi: 10.1556/030.2023.02082. Online ahead of print.ABSTRACTIrreversible pulpitis is an inflammation of the tooth pulp caused by an opportunity-driven invasion of the pulp space by oral microbiota typically prevalent in the oral cavity. Microbial organisms are extensively recognised to be the fundamental cause of endodontic infections and treatment failures. Previously, bacterial species responsible for these infections were largely recognised using conventional microbial culture techniques, lending credence to the widely held belief that anaerobic Gram-negative bacteria frequently enter the pulp space and trigger endodontic infections. The advent of novel technologies grants the advantage of detecting and studying microbial populations via an amalgamation of the modern "Omics" techniques and meticulous bioinformatics analysis, additionally detecting the metatranscriptome, metaproteome and metabolome along with the metagenome. Amongst these analytical strategies, metagenomic analyses are essentially pragmatic for investigating the oral microbiome. Metagenomics favor not only assessment of microbial composition in diseased conditions, but also contributes to detection of novel, potentially pathogenic species inclusive of non-viable bacteria. The present review describes current knowledge of root canal microbiome, including its composition and functional attributes, the novel strategies available for detection of microbiome as well as challenges associated and provides some crucial pointers for areas of future research.PMID:37505986 | DOI:10.1556/030.2023.02082

Vet Sci. 2023 Jul 5;10(7):437. doi: 10.3390/vetsci10070437.ABSTRACTAnemoside B4 has a good curative effect on cows with CM; however, its impact on their metabolic profiles is unclear. Based on similar somatic cell counts and clinical symptoms, nine healthy dairy cows and nine cows with CM were selected, respectively. Blood samples were collected from cows with mastitis on the day of diagnosis. Cows with mastitis were injected with anemoside B4 (0.05 mL/kg, once daily) for three consecutive days, and healthy cows were injected with the same volume of normal saline. Subsequently, blood samples were collected. The plasma metabolic profiles were analyzed using untargeted mass spectrometry, and the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in serum were evaluated via ELISA. The cows with CM showed increased concentrations of IL-1β, IL-6, and TNF-α (p < 0.05). After treatment with anemoside B4, the concentrations of IL-1β, IL-6, and TNF-α were significantly decreased (p < 0.01). Untargeted metabolomics analysis showed that choline, glycocholic acid, PC (18:0/18:1), 20-HETE, PGF3α, and oleic acid were upregulated in cows with CM. After treatment with anemoside B4, the concentrations of PC (16:0/16:0), PC (18:0/18:1), linoleic acid, eicosapentaenoic acid, phosphorylcholine, and glycerophosphocholine were downregulated, while the LysoPC (14:0), LysoPC (18:0), LysoPC (18:1), and cis-9-palmitoleic acid were upregulated. This study indicated that anemoside B4 alleviated the inflammatory response in cows with CM mainly by regulating lipid metabolism.PMID:37505842 | DOI:10.3390/vetsci10070437

Environ Health Perspect. 2023 Jul;131(7):74004. doi: 10.1289/EHP13275. Epub 2023 Jul 28.NO ABSTRACTPMID:37505745 | DOI:10.1289/EHP13275

Toxins (Basel). 2023 Jun 28;15(7):421. doi: 10.3390/toxins15070421.ABSTRACTAlternariol is a metabolite produced by Alternaria fungus that can contaminate a variety of food and feed materials. The objective of the present paper was to provide a prediction of Phase I and II metabolites of alternariol and a detailed ADME/Tox profile for alternariol and its metabolites using an in silico working model based on the MetaTox, SwissADME, pKCMS, and PASS online computational programs. A number of 12 metabolites were identified as corresponding to the metabolomic profile of alternariol. ADME profile for AOH and predicted metabolites indicated a moderate or high intestinal absorption probability but a low probability to penetrate the blood-brain barrier. In addition to cytotoxic, mutagenic, carcinogenic, and endocrine disruptor effects, the computational model has predicted other toxicological endpoints for the analyzed compounds, such as vascular toxicity, haemato-toxicity, diarrhea, and nephrotoxicity. AOH and its metabolites have been predicted to act as a substrate for different isoforms of phase I and II drug-metabolizing enzymes and to interact with the response to oxidative stress. In conclusion, in silico methods can represent a viable alternative to in vitro and in vivo tests for the prediction of mycotoxins metabolism and toxicity.PMID:37505690 | DOI:10.3390/toxins15070421

Toxins (Basel). 2023 Jun 26;15(7):414. doi: 10.3390/toxins15070414.ABSTRACTPeanut seeds are susceptible to Aspergillus flavus infection, which has a severe impact on the peanut industry and human health. However, the molecular mechanism underlying this defense remains poorly understood. The aim of this study was to analyze the changes in differentially expressed genes (DEGs) and differential metabolites during A. flavus infection between Zhonghua 6 and Yuanza 9102 by transcriptomic and metabolomic analysis. A total of 5768 DEGs were detected in the transcriptomic study. Further functional analysis showed that some DEGs were significantly enriched in pectinase catabolism, hydrogen peroxide decomposition and cell wall tissues of resistant varieties at the early stage of infection, while these genes were differentially enriched in the middle and late stages of infection in the nonresponsive variety Yuanza 9102. Some DEGs, such as those encoding transcription factors, disease course-related proteins, peroxidase (POD), chitinase and phenylalanine ammonialyase (PAL), were highly expressed in the infection stage. Metabolomic analysis yielded 349 differential metabolites. Resveratrol, cinnamic acid, coumaric acid, ferulic acid in phenylalanine metabolism and 13S-HPODE in the linolenic acid metabolism pathway play major and active roles in peanut resistance to A. flavus. Combined analysis of the differential metabolites and DEGs showed that they were mainly enriched in phenylpropane metabolism and the linolenic acid metabolism pathway. Transcriptomic and metabolomic analyses further confirmed that peanuts infected with A. flavus activates various defense mechanisms, and the response to A. flavus is more rapid in resistant materials. These results can be used to further elucidate the molecular mechanism of peanut resistance to A. flavus infection and provide directions for early detection of infection and for breeding peanut varieties resistant to aflatoxin contamination.PMID:37505683 | DOI:10.3390/toxins15070414

Photochem Photobiol Sci. 2023 Jul 28. doi: 10.1007/s43630-023-00455-9. Online ahead of print.ABSTRACTUV-B radiation regulates numerous morphogenic, biochemical and physiological responses in plants, and can stimulate some responses typically associated with other abiotic and biotic stimuli, including invertebrate herbivory. Removal of UV-B from the growing environment of various plant species has been found to increase their susceptibility to consumption by invertebrate pests, however, to date, little research has been conducted to investigate the effects of UV-B on crop susceptibility to field pests. Here, we report findings from a multi-omic and genetic-based study investigating the mechanisms of UV-B-stimulated resistance of the crop, Brassica napus (oilseed rape), to herbivory from an economically important lepidopteran specialist of the Brassicaceae, Plutella xylostella (diamondback moth). The UV-B photoreceptor, UV RESISTANCE LOCUS 8 (UVR8), was not found to mediate resistance to this pest. RNA-Seq and untargeted metabolomics identified components of the sinapate/lignin biosynthetic pathway that were similarly regulated by UV-B and herbivory. Arabidopsis mutants in genes encoding two enzymes in the sinapate/lignin biosynthetic pathway, CAFFEATE O-METHYLTRANSFERASE 1 (COMT1) and ELICITOR-ACTIVATED GENE 3-2 (ELI3-2), retained UV-B-mediated resistance to P. xylostella herbivory. However, the overexpression of B. napus COMT1 in Arabidopsis further reduced plant susceptibility to P. xylostella herbivory in a UV-B-dependent manner. These findings demonstrate that overexpression of a component of the sinapate/lignin biosynthetic pathway in a member of the Brassicaceae can enhance UV-B-stimulated resistance to herbivory from P. xylostella.PMID:37505444 | DOI:10.1007/s43630-023-00455-9

Hepatology. 2023 Jul 24. doi: 10.1097/HEP.0000000000000542. Online ahead of print.ABSTRACTBACKGROUND: Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or "at-risk MASH" is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH.METHODS: We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers. Patients underwent laboratory assessment and liver biopsy for MASLD. Based on 12 lipids, body mass index, aspartate aminotransferase, and alanine aminotransferase, the MASEF score was developed to identify at-risk MASH and compared to the FibroScan-AST (FAST) score. We further compared the performance of a FIB-4 + MASEF algorithm to that of FIB-4 + liver stiffness measurements (LSM) by transient elastography (VCTE).RESULTS: The diagnostic performance of the MASEF score showed an area under the receiver-operating characteristic curve, sensitivity, specificity, positive and negative predictive values of 0.76 (95% CI 0.72-0.79), 0.69, 0.74, 0.53, and 0.85 in the derivation cohort, and 0.79 (95% CI 0.75-0.83), 0.78, 0.65, 0.48, and 0.88 in the validation cohort, while FAST performance in the validation cohort was 0.74 (95% CI 0.68-0.79; p = 0.064), 0.58, 0.79, 0.67, and 0.73, respectively. FIB-4 + MASEF showed similar overall performance compared to FIB-4 + LSM by VCTE (p = 0.69) to identify at-risk MASH.CONCLUSION: MASEF is a promising diagnostic tool for the assessment of at-risk MASH. It could be used alternatively to LSM by VCTE in the algorithm that is currently recommended by several guidance publications.PMID:37505221 | DOI:10.1097/HEP.0000000000000542

Clin Sci (Lond). 2023 Jul 28:CS20230372. doi: 10.1042/CS20230372. Online ahead of print.ABSTRACTMaternal overnutrition can dramatically increase the susceptibility of offspring to metabolic diseases, whereas maternal exercise may improve glucose metabolism in offspring. However, the underlying mechanism programming the intergenerational effects of maternal exercise on the benefits of glucose metabolism has not been fully elaborated. C57BL/6 female mice were randomly assigned to four subgroups according to a diet and exercise paradigm before and during pregnancy as follows: NC (fed with normal chow diet and sedentary), NCEx (fed with normal chow diet and running), HF (fed with high-fat diet and sedentary), and HFEx (fed with high-fat diet and running). Integrative 16S rDNA sequencing and mass spectrometry-based metabolite profiling were synchronously performed to characterize the effects of maternal exercise on the gut microbiota composition and metabolite alterations in offspring. Maternal exercise, acting as a natural pharmaceutical intervention, prevented deleterious effects on glucose metabolism in offspring. 16S rDNA sequencing revealed remarkable changes in the gut microbiota composition in offspring. Metabolic profiling indicated multiple altered metabolites, which were enriched in butanoate metabolism signaling in offspring. We further found that maternal exercise could mediate gene expression related to intestinal gluconeogenesis in offspring. In conclusion, our study indicated that maternal running significantly improved glucose metabolism in offspring and counteracted the detrimental effects of maternal high-fat feeding before and during pregnancy. We further demonstrated that maternal voluntary wheel running could integratively program the gut microbiota composition and fecal metabolite changes and then regulate butanoate metabolism and mediate intestinal gluconeogenesis in offspring.PMID:37505199 | DOI:10.1042/CS20230372

Mar Drugs. 2023 Jul 19;21(7):409. doi: 10.3390/md21070409.ABSTRACTMetabolic syndrome (MetS) is a global health problem, and EPA/DHA-enriched phospholipids (EPA/DHA-PLs) have been found to have positive effects on MetS improvement. Currently, research on EPA/DHA-PL mainly focuses on special and rare seafood, such as phospholipids derived from krill, sea cucumber, squid, and fish roe. However, it has been recently demonstrated that abundant EPA/DHA-PL can also be found in bulk fish and its by-products. Nonetheless, there is still limited research on the biological activities of EPA/DHA-PL derived from these sources. The aim of this study was to investigate the effect of phospholipid extracts from the heads of salmon and silver carp (S-PLE and SC-PLE) on the high-fat-diet-induced MetS in C57/BL mice. After an 8-week intervention, both SC-PLE and S-PLE had a significant ameliorating effect on MetS. Moreover, SC-PLE was more effective than S-PLE in reducing liver inflammation and fasting glucose. Both of the PL extracts were able to regulate the expression of key genes in lipid synthesis, fatty acid β-oxidation, and insulin signaling pathways. Compared with S-PLE, dietary SC-PLE had a greater influence on liver metabolomics. Pathway enrichment analysis showed that the differential metabolites of SC-PLE were mainly involved in arachidonic acid metabolism and glutathione metabolism. The results indicated that the different metabolic regulation methods of S-PLE and SC-PLE could be related to their variant molecular composition in EPA/DHA-PL.PMID:37504940 | DOI:10.3390/md21070409

J Fungi (Basel). 2023 Jun 27;9(7):704. doi: 10.3390/jof9070704.ABSTRACTThe genus Fusarium is well-known to comprise many pathogenic fungi that affect cereal crops worldwide, causing severe damage to agriculture and the economy. In this study, an endophytic fungus designated Fusarium sp. VM-40 was isolated from a healthy specimen of the traditional European medicinal plant Vinca minor. Our morphological characterization and phylogenetic analysis reveal that Fusarium sp. VM-40 is closely related to Fusarium paeoniae, belonging to the F. tricinctum species complex (FTSC), the genomic architecture and secondary metabolite profile of which have not been investigated. Thus, we sequenced the whole genome of Fusarium sp. VM-40 with the new Oxford Nanopore R10.4 flowcells. The assembled genome is 40 Mb in size with a GC content of 47.72%, 15 contigs (≥50,000 bp; N 50~4.3 Mb), and 13,546 protein-coding genes, 691 of which are carbohydrate-active enzyme (CAZyme)-encoding genes. We furthermore predicted a total of 56 biosynthetic gene clusters (BGCs) with antiSMASH, 25 of which showed similarity with known BGCs. In addition, we explored the potential of this fungus to produce secondary metabolites through untargeted metabolomics. Our analyses reveal that this fungus produces structurally diverse secondary metabolites of potential pharmacological relevance (alkaloids, peptides, amides, terpenoids, and quinones). We also employed an epigenetic manipulation method to activate cryptic BGCs, which led to an increased abundance of several known compounds and the identification of several putative new compounds. Taken together, this study provides systematic research on the whole genome sequence, biosynthetic potential, and metabolome of the endophytic fungus Fusarium sp. VM-40.PMID:37504693 | DOI:10.3390/jof9070704

J Fungi (Basel). 2023 Jun 21;9(7):693. doi: 10.3390/jof9070693.ABSTRACTUtilizing mycoremediation is an important direction for managing heavy metal pollution. Zn2+ pollution has gradually become apparent, but there are few reports about its pollution remediation. Here, the Zn2+ remediation potential of Paraisaria dubia, an anamorph of the entomopathogenic fungus Ophiocordyceps gracilis, was explored. There was 60% Zn2+ removed by Paraisaria dubia mycelia from a Zn2+-contaminated medium. To reveal the Zn2+ tolerance mechanism of Paraisaria dubia, transcriptomic and metabolomic were executed. Results showed that Zn2+ caused a series of stress responses, such as energy metabolism inhibition, oxidative stress, antioxidant defense system disruption, autophagy obstruction, and DNA damage. Moreover, metabolomic analyses showed that the biosynthesis of some metabolites was affected against Zn2+ stress. In order to improve the tolerance to Zn2+ stress, the metabolic mechanism of metal ion transport, extracellular polysaccharides (EPS) synthesis, and microcycle conidiation were activated in P. dubia. Remarkably, the formation of microcycle conidiation may be triggered by reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling pathways. This study supplemented the gap of the Zn2+ resistance mechanism of Paraisaria dubia and provided a reference for the application of Paraisaria dubia in the bioremediation of heavy metals pollution.PMID:37504682 | DOI:10.3390/jof9070693

Curr Issues Mol Biol. 2023 Jun 30;45(7):5558-5574. doi: 10.3390/cimb45070351.ABSTRACTDespite the existence of effective drugs used to treat inflammatory bowel disease (IBD), many patients fail to respond or lose response over time. Further, many drugs can carry serious adverse effects, including increased risk of infections and malignancies. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD and how the microbiome and metabolome play a role has not been explored extensively. We aimed to establish whether saffron treatment modulates the host microbiome and metabolic profile in experimental colitis. Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron in a dose of 20 mg/kg body weight or vehicle through daily gavage. On day 10, stool pellets from mice were collected and analyzed to assess saffron's effect on fecal microbiota and metabolites through 16S rRNA sequencing and untargeted primary metabolite analysis. Saffron treatment maintained gut microbiota homeostasis by counter-selecting pro-inflammatory bacteria and maintained Firmicutes/Bacteroides ratio, which was otherwise disturbed by DSS treatment. Several metabolites (uric acid, cholesterol, 2 hydroxyglutaric acid, allantoic acid, 2 hydroxyhexanoic acid) were altered significantly with saffron treatment in DSS-treated mice, and this might play a role in mediating saffron's colitis-mitigating effects. These data demonstrate saffron's therapeutic potential, and its protective role is modulated by gut microbiota, potentially acting through changes in metabolites.PMID:37504267 | DOI:10.3390/cimb45070351

Biosensors (Basel). 2023 Jul 18;13(7):743. doi: 10.3390/bios13070743.ABSTRACTThe need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent years, the technology of paper-based microfluidic analytical devices (μPADs) has undergone rapid development and now provides a feasible, low-cost alternative to traditional rapid tests for detecting harmful compounds. In fact, µPADs have been developed to detect toxic molecules (arsenic, cyanide, ethanol, and nitrite), drugs, and drugs of abuse (benzodiazepines, cathinones, cocaine, fentanyl, ketamine, MDMA, morphine, synthetic cannabinoids, tetrahydrocannabinol, and xylazine), and also psychoactive substances used for drug-facilitated crimes (flunitrazepam, gamma-hydroxybutyric acid (GHB), ketamine, metamizole, midazolam, and scopolamine). The present report critically evaluates the recent developments in paper-based devices, particularly in detection methods, and how these new analytical tools have been tested in forensic and clinical toxicology, also including future perspectives on their application, such as multisensing paper-based devices, microfluidic paper-based separation, and wearable paper-based sensors.PMID:37504142 | DOI:10.3390/bios13070743

Chem Biodivers. 2023 Jul 28:e202300346. doi: 10.1002/cbdv.202300346. Online ahead of print.ABSTRACTPleurotus ostreatus is an edible fungus with high nutritional value that uses industrial and agricultural lignocellulosic residues as substrates for growth and reproduction. Understanding their growth metabolic dynamics on agro-industrial wastes would help to develop economically viable and eco-friendly biotechnological strategies for food production. Thus, we used UHPLC-MS/MS and GNPS as an innovative approach to investigate the chemical composition of two strains of P. ostreatus, coded as BH (Black Hirataki) and WH (White Hirataki), grown on sisal waste mixture (SW) supplemented with 20% cocoa almond tegument (CAT) or 20% of wheat bran (WB). Metabolite dereplication allowed the identification of 53 metabolites, which included glycerophospholipids, fatty acids, monoacylglycerols, steroids, carbohydrates, amino acids, and flavonoids. This is the first report of the identification of these compounds in P. ostreatus, except for the steroid ergosterol. Most of the metabolites described in this work possess potential biological activities, which support the nutraceutical properties of P. ostreatus. Thus, the results of this study provide essential leads to the understanding of white-rot fungi chemical plasticity aiming at developing alternative biotechnologies strategies for waste recycling.PMID:37503864 | DOI:10.1002/cbdv.202300346

Front Immunol. 2023 Jul 12;14:1193235. doi: 10.3389/fimmu.2023.1193235. eCollection 2023.ABSTRACTTumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. TAMs showed different activation states that can be represent by the two extremes of the complex profile of macrophages biology, the M1-like phenotype (pro-inflammatory activity) and the M2-like phenotype (anti-inflammatory activity). Based on the tumor type, and grades, TAMs can acquire different functions and properties; usually, the M1-like phenotype is typical of early tumor stages and is associated to an anti-tumor activity, while M2-like phenotype has a pro-inflammatory activity and is related to a poor patients' prognosis. The classification of macrophages into M1/M2 groups based on well-defined stimuli does not model the infinitely more complex tissue milieu where macrophages (potentially of different origin) would be exposed to multiple signals in different sequential order. This review aims to summarize the recent mass spectrometry-based (MS-based) metabolomics findings about the modifications of metabolism in TAMs polarization in different tumors. The published data shows that MS-based metabolomics is a promising tool to help better understanding TAMs metabolic phenotypes, although it is still poorly applied for TAMs metabolism. The knowledge of key metabolic alterations in TAMs is an essential step for discovering TAMs polarization novel biomarkers and developing novel therapeutic approaches targeting TAM metabolism to repolarize TAMs towards their anti-tumor phenotype.PMID:37503340 | PMC:PMC10368868 | DOI:10.3389/fimmu.2023.1193235

bioRxiv. 2023 Jul 17:2023.07.14.548964. doi: 10.1101/2023.07.14.548964. Preprint.ABSTRACTMetabolomics is a powerful tool for uncovering biochemical diversity in a wide range of organisms, and metabolic network modeling is commonly used to frame results in the context of a broader homeostatic system. However, network modeling of poorly characterized, non-model organisms remains challenging due to gene homology mismatches. To address this challenge, we developed Metabolic Interactive Nodular Network for Omics (MINNO), a web-based mapping tool that takes in empirical metabolomics data to refine metabolic networks for both model and unusual organisms. MINNO allows users to create and modify interactive metabolic pathway visualizations for thousands of organisms, in both individual and multi-species contexts. Herein, we demonstrate an important application of MINNO in elucidating the metabolic networks of understudied species, such as those of the Borrelia genus, which cause Lyme disease and relapsing fever. Using a hybrid genomics-metabolomics modeling approach, we constructed species-specific metabolic networks for three Borrelia species. Using these empirically refined networks, we were able to metabolically differentiate these genetically similar species via their nucleotide and nicotinate metabolic pathways that cannot be predicted from genomic networks. These examples illustrate the use of metabolomics for the empirical refining of genetically constructed networks and show how MINNO can be used to study non-model organisms.PMID:37503268 | PMC:PMC10370097 | DOI:10.1101/2023.07.14.548964