PubMed

J Agric Food Chem. 2023 Jun 22. doi: 10.1021/acs.jafc.3c02179. Online ahead of print.ABSTRACTMillet and its components have received much extensive attention for their health benefits in mitigating metabolic diseases. Foxtail millet is rich in phytochemicals, including oil. However, the hypoglycemic capacity of foxtail millet oil has yet to be fully investigated. The present study explored the effects of consuming this oil as the lipid extract of foxtail millet (LEFM) on intestinal microbiota composition and metabolic function in diabetic mice. After eight weeks of LEFM supplementation, the blood glucose, insulin resistance index, and lipid accumulation of diabetic mice were significantly decreased. In addition, LEFM feeding modulated gut microbiota composition, reduced the abundance of harmful bacteria (Escherichia-Shigella, Peptococcus, and norank_f_Oscillospiraceae), induced a bloom of probiotics, especially short-chain fatty acid (SCFA)-producing bacteria (Adlercreutzia, Faecalibaculum, and Bifidobacterium), and increased SCFAs concentration. LEFM treatment altered serum metabolite levels, for instance, greatly increasing the levels of l-carnitine and l-glutamine and reducing S-acetyldihydrolipoamide-E and sphingosine. Overall, improvements in gut microbiota and metabolic function were associated with the hypoglycemic potential of LEFM.PMID:37347971 | DOI:10.1021/acs.jafc.3c02179

Environ Toxicol. 2023 Jun 22. doi: 10.1002/tox.23877. Online ahead of print.ABSTRACTThe environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography-mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up-regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA-induced hepatotoxicity by reversing the occurrence of ferroptosis.PMID:37347548 | DOI:10.1002/tox.23877

JCI Insight. 2023 Jun 22:e164646. doi: 10.1172/jci.insight.164646. Online ahead of print.ABSTRACTVincristine is a widely used chemotherapeutic drug for the treatment of multiple malignant diseases that causes a dose-limiting peripheral neurotoxicity. There is no clinically effective preventative treatment for vincristine-induced sensory peripheral neurotoxicity (VIPN), and mechanistic details of this side effect remain poorly understood. We hypothesized that VIPN is dependent on transporter-mediated vincristine accumulation in dorsal root ganglion neurons. Using a xenobiotic transporter screen, we identified OATP1B3 as a neuronal transporter regulating the uptake of vincristine. In addition, genetic or pharmacological inhibition of the murine orthologue transporter OATP1B2 protected mice from various hallmarks of VIPN, including mechanical-induced allodynia, thermal hyperalgesia, and changes in digital maximal action potential amplitudes and neuronal morphology, without negatively affecting plasma levels or antitumor effects of vincristine. Finally, we identified α-tocopherol from an untargeted metabolomics analysis as a circulating endogenous biomarker of neuronal OATP1B2 function, which could serve as a future companion diagnostic to guide dose selection of OATP1B-type transport modulators given in combination with vincristine to prevent VIPN. Collectively, our findings shed light on the fundamental basis of VIPN and provide a rationale for the clinical development of transporter inhibitors to prevent this debilitating side effect.PMID:37347545 | DOI:10.1172/jci.insight.164646

J Diabetes Investig. 2023 Jun 22. doi: 10.1111/jdi.14041. Online ahead of print.ABSTRACTAIMS/INTRODUCTION: Distal symmetric polyneuropathy (DSPN) is a common complication of type 2 diabetes mellitus, but the underlining mechanisms have not yet been elucidated. The current study was designed to screen the feature metabolites classified as potential biomarkers, and to provide deeper insights into the underlying distinctive metabolic changes during disease progression.MATERIALS AND METHODS: Plasma metabolite profiles were obtained by the ultra-high liquid chromatography coupled to tandem mass spectrometry method from healthy control participants, patients with type 2 diabetes mellitus and patients with DSPN. Potential biomarkers were selected through comprehensive analysis of statistically significant differences between groups.RESULTS: Overall, 938 metabolites were identified. Among them, 12 metabolites (dimethylarginine, N6-acetyllysine, N-acetylhistidine, N,N,N-trimethyl-alanylproline betaine, cysteine, 7-methylguanine, N6-carbamoylthreonyladenosine, pseudouridine, 5-methylthioadenosine, N2,N2-dimethylguanosine, aconitate and C-glycosyl tryptophan) were identified as the specific biomarkers. The content of 12 metabolites were significantly higher in the DSPN group compared with the other two groups. Additionally, they showed good performance to discriminate the DSPN state. Correlation analyses showed that the levels of 12 metabolites might be more closely related to the glucose metabolic changes, followed by the levels of lipid metabolism.CONCLUSIONS: The finding of the 12 signature metabolites might provide a novel perspective for the pathogenesis of DSPN. Future studies are required to test this observation further.PMID:37347226 | DOI:10.1111/jdi.14041

Microbiol Spectr. 2023 Jun 22:e0506322. doi: 10.1128/spectrum.05063-22. Online ahead of print.ABSTRACTSeveral studies have described the contribution of glutamate-transforming microbiota to the development of chronic ailments. For instance, the blood concentration of glutamate is higher in some patients with fibromyalgia, chronic fatigue, and pain. Taking advantage of a naturally occurring strain of Bifidobacterium that is able to transform glutamate in γ-aminobutyric caid (GABA), B. adolescentis IPLA60004, we designed a placebo-controlled intervention to test if the presence of this GABA-producing bifidobacteria in mice was able to impact the concentration of glutamate in the blood in comparison with the administration of other strain of the same species lacking the genes of the glutamate decarboxylase (gad) cluster. Animals were fed every day with 8 log CFU of bacteria in a sterilized milk vehicle for 14 days. Samples from feces and blood were collected during this period, and afterwards animals were sacrificed, tissues were taken from different organs, and the levels of different metabolites were analyzed by ultrahigh-performance liquid chromatography coupled to mass spectrometry. The results showed that both bacterial strains orally administered survived in the fecal content, and animals fed B. adolescentis IPLA60004 showed a significant reduction of their glutamate serum concentration, while a nonsignificant decrease was observed for animals fed a reference strain, B. adolescentis LGM10502. The variations observed in GABA were influenced by the gender of the animals, and no significant changes were observed in different tissues of the brain. These results suggest that orally administered GABA-producing probiotics could reduce the glutamate concentration in blood, opening a case for a clinical trial study in chronic disease patients. IMPORTANCE This work presents the results of a trial using mice as a model that were fed with a bacterial strain of the species B. adolescentis, which possesses different active genes capable of degrading glutamate and converting it into GABA. Indeed, the bacterium is able to survive the passage through the gastric tract and, more importantly, the animals reduce over time the concentration of glutamate in their blood. The importance of this result lies in the fact that several chronic ailments, such as fibromyalgia, are characterized by an increase in glutamate. Our results indicate that an oral diet with this probiotic-type bacteria could reduce the concentration of glutamate and, therefore, reduce the symptoms associated with the excess of this neurotransmitter.PMID:37347184 | DOI:10.1128/spectrum.05063-22

Front Nutr. 2023 Jun 6;10:1158473. doi: 10.3389/fnut.2023.1158473. eCollection 2023.ABSTRACTINTRODUCTION: Citrus fruits are one of the most frequently counterfeited processed products in the world. In the juice production alone, the peels, divided into flavedo and albedo, are the main waste product. The extracts of this by-product are enriched with many bioactive substances. Newer extraction techniques generally have milder extraction conditions with simultaneous improvement of the extraction process.METHODS: This study presents a combinatorial approach utilizing data-independent acquisition-based ion mobility spectrometry coupled to tandem mass spectrometry. Integrating orthogonal collision cross section (CCS) data matching simultaneously improves the confidence in metabolite identification in flavedo and albedo tissues from Citrus sinensis. Furthermore, four different extraction approaches [conventional, ultrasonic, High Hydrostatic Pressure (HHP) and Pulsed Electric Field (PEF)] with various optimized processing conditions were compared in terms of antioxidant effects and flavonoid profile particularly polymethoxy flavones (PMFs).RESULTS: A total number of 57 metabolites were identified, 15 of which were present in both flavedo and albedo, forming a good qualitative overlapping of distributed flavonoids. For flavedo samples, the antioxidant activity was higher for PEF and HHP treated samples compared to other extraction methods. However, ethyl acetate extract exhibited the highest antioxidant effects in albedo samples attributed to different qualitative composition content rather than various quantities of same metabolites. The optimum processing conditions for albedo extraction using HHP and PEF were 200 MPa and 15 kJ/kg at 10 kV, respectively. While, HHP at medium pressure (400 MPa) and PEF at 15 kJ/kg/3 kV were the optimum conditions for flavedo extraction.CONCLUSION: Chemometric analysis of the dataset indicated that orange flavedo can be a valid source of soluble phenolic compounds especially PMFs. In order to achieve cross-application of production, future study should concentrate on how citrus PMFs correlate with biological engineering techniques such as breeding, genetic engineering, and fermentation engineering.PMID:37346911 | PMC:PMC10279959 | DOI:10.3389/fnut.2023.1158473

Front Microbiol. 2023 Jun 6;14:1211259. doi: 10.3389/fmicb.2023.1211259. eCollection 2023.ABSTRACTOBJECTIVES: Inflammatory bowel disease (IBD) is a chronic lifelong inflammatory disease. Probiotics such as Bifidobacterium longum are considered to be beneficial to the recovery of intestinal inflammation by interaction with gut microbiota. Our goals were to define the effect of the exclusive use of BAA2573 on dextran sulfate sodium (DSS)-induced colitis, including improvement of symptoms, alleviation of histopathological damage, and modulation of gut microbiota.METHODS: In the present study, we pretreated C57BL/6J mice with Bifidobacterium longum BAA2573, one of the main components in an over-the-counter (OTC) probiotic mixture BIFOTO capsule, before modeling with DSS. 16S rDNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based non-targeted metabolomic profiling were performed with the collected feces.RESULTS: We found that pretreatment of Bifidobacterium longum BAA2573 given by gavage significantly improved symptoms and histopathological damage in DSS-induced colitis mice. After the BAA2573 intervention, 57 genera and 39 metabolites were significantly altered. Pathway enrichment analysis demonstrated that starch and sucrose metabolism, vitamin B6 metabolism, and sphingolipid metabolism may contribute to ameliorating colitis. Moreover, we revealed that the gut microbiome and metabolites were interrelated in the BAA2573 intervention group, while Alistipes was the core genus.CONCLUSION: Our study demonstrates the impact of BAA2573 on the gut microbiota and reveals a possible novel adjuvant therapy for IBD patients.PMID:37346749 | PMC:PMC10280014 | DOI:10.3389/fmicb.2023.1211259

Front Physiol. 2023 Jun 6;14:1178869. doi: 10.3389/fphys.2023.1178869. eCollection 2023.ABSTRACTOrganisms adapt to changes in their environment to survive. The emergence of predators is an example of environmental change, and organisms try to change their external phenotypic systems and physiological mechanisms to adapt to such changes. In general, prey exhibit different phenotypes to predators owing to historically long-term prey-predator interactions. However, when presented with a novel predator, the extent and rate of phenotypic plasticity in prey are largely unknown. Therefore, exploring the physiological adaptive response of organisms to novel predators is a crucial topic in physiology and evolutionary biology. Counterintuitively, Xenopus tropicalis tadpoles do not exhibit distinct external phenotypes when exposed to new predation threats. Accordingly, we examined the brains of X. tropicalis tadpoles to understand their response to novel predation pressure in the absence of apparent external morphological adaptations. Principal component analysis of fifteen external morphological parameters showed that each external morphological site varied nonlinearly with predator exposure time. However, the overall percentage change in principal components during the predation threat (24 h) was shown to significantly (p < 0.05) alter tadpole morphology compared with that during control or 5-day out treatment (5 days of exposure to predation followed by 5 days of no exposure). However, the adaptive strategy of the altered sites was unknown because the changes were not specific to a particular site but were rather nonlinear in various sites. Therefore, RNA-seq, metabolomic, Ingenuity Pathway Analysis, and Kyoto Encyclopedia of Genes and Genomes analyses were performed on the entire brain to investigate physiological changes in the brain, finding that glycolysis-driven ATP production was enhanced and ß-oxidation and the tricarboxylic acid cycle were downregulated in response to predation stress. Superoxide dismutase was upregulated after 6 h of exposure to new predation pressure, and radical production was reduced. Hemoglobin was also increased in the brain, forming oxyhemoglobin, which is known to scavenge hydroxyl radicals in the midbrain and hindbrain. These suggest that X. tropicalis tadpoles do not develop external morphological adaptations that are positively correlated with predation pressure, such as tail elongation, in response to novel predators; however, they improve their brain functionality when exposed to a novel predator.PMID:37346489 | PMC:PMC10279953 | DOI:10.3389/fphys.2023.1178869

Emerg Med Int. 2023 Jun 13;2023:2590115. doi: 10.1155/2023/2590115. eCollection 2023.ABSTRACTCurrent prognostic biomarkers for sepsis have limited sensitivity and specificity. This study aimed to investigate dynamic lipid metabolomics and their association with septic immune response and clinical outcomes of sepsis. This prospective cohort study included patients with sepsis who met the Sepsis 3.0 criteria. On hospitalization days 1 (D1) and 7 (D7), plasma samples were collected, and patients underwent liquid chromatography with tandem mass spectrometry. A total of 40 patients were enrolled in the study, 24 (60%) of whom were men. The median age of the enrolled patients was 81 (68-84) years. Thirty-one (77.5%) patients had a primary infection site of the lung. Participants were allocated to the survivor (25 cases) and nonsurvivor (15 cases) groups based on their 28-day survival status. Ultimately, a total of 113 lipids were detected in plasma samples on D 1 and D 7, of which 42 lipids were most abundant in plasma samples. The nonsurvival group had significantly lower lipid expression levels in lysophosphatidylcholine (LysoPC) (16 : 0, 17 : 0,18 : 0) and 18 : 1 SM than those in the survival group (p < 0.05) on D7-D1. The correlation analysis showed that D7-D1 16 : 0 LysoPC (r = 0.367, p = 0.036),17 : 0 LysoPC (r = 0.389, p = 0.025) and 18 : 0 LysoPC(r = 0.472, p = 0.006) levels were positively correlated with the percentage of CD3+ T cell in the D7-D1. Plasma LysoPC and SM changes may serve as prognostic biomarkers for sepsis, and lipid metabolism may play a role in septic immune disturbances.PMID:37346225 | PMC:PMC10281824 | DOI:10.1155/2023/2590115

Chem Biodivers. 2023 Jun 22:e202300552. doi: 10.1002/cbdv.202300552. Online ahead of print.ABSTRACTLight-emitting plants (LEPs) provides light in areas without electricity. The phosphorescent compound was used as a lighting material for LEP development. However, using the phosphorescent compound for LEPs development required optimization and phytotoxicity evaluation. Strontium aluminate (SrAl2O4) is a phosphorescent compound that can glow for a long time and is easily recharged by visible light. In this study, using SrAl2O4 to develop LEPs was evaluated. Additionally, plant stress under SrAl2O4 was investigated. Metabolomic analysis can explain the possible mechanism of plants' stress under SrAl2O4. After, injecting 3 mL of 5% (w/v) SrAl2O4 products 1, 2, and 3 into the stem of Ipomoea aquatica, the result showed that SrAl2O4 products 2 and 3 caused oxidative stress. The metabolomic analysis also indicated that I. aquatica responded to SrAl2O4 product 1 by increasing pipecolic acid and salicylic acid, while I. aquatica injected with SrAl2O4 products 2 and 3 showed a decrease in salicylic acid around 0.005 and 0.061-fold, respectively, compared to control plants. and an excess accumulation of MDA around 10.00-12.00 µmol g-1 FW. A 15% concentration of SrAl2O4 can be used for LEPs development, enabling photoemission 18-fold for 50 minutes. SrAl2O4 product 1 has the potential to be a material for LEPs.PMID:37345919 | DOI:10.1002/cbdv.202300552

J Am Heart Assoc. 2023 Jun 22:e029542. doi: 10.1161/JAHA.123.029542. Online ahead of print.ABSTRACTBackground Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post-transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25-1.90]; P<0.001), with similar effects in each validation cohort. This metabolite score of diastolic function was simultaneously associated with measures of multimorbidity, suggesting a metabolic link between cardiac and noncardiac state in aortic stenosis. Conclusions Metabolite profiles of cardiac structure identify individuals at high risk for death following transcatheter aortic valve implantation and concurrent multimorbidity. These results call for efforts to address potentially reversible metabolic biology associated with risk to optimize post-transcatheter aortic valve implantation recovery, rehabilitation, and survival.PMID:37345820 | DOI:10.1161/JAHA.123.029542

J Agric Food Chem. 2023 Jun 22. doi: 10.1021/acs.jafc.3c01881. Online ahead of print.ABSTRACT3,5,6,7,8,3',4'-Heptamethoxyflavone (HMF) could prevent obesity and hyperlipidemia, but its effects on gut microbiota and fecal metabolites remain unclear. Here, the effect of HMF on metabolic syndrome (MS) was evaluated in high-fat diet (HFD)-fed mice, and its underlying mechanisms were revealed by integrative metagenomic and metabolomic analyses. We demonstrated that HMF could effectively ameliorate HFD-induced MS by alleviating body-weight gain, fat accumulation, hepatic steatosis, and lipid and glucose abnormalities. HMF significantly altered the gut microbiota composition in HFD-fed mice with enrichment of short-chain fatty acid (SCFA)- and bile acid-producing beneficial bacteria and inhibition of harmful bacteria. Also, HMF improved microbial functions by up-regulating bile acid metabolism and down-regulating fatty acid metabolism and inflammatory response-related pathways. Consistent with the gut microbial changes, HMF altered the fecal metabolite profile of HFD-fed mice, mainly characterized by increasing SCFA and several bile acid levels as well as lowering several lysophospholipids and fatty acid levels. Correlation analysis indicated that three key species Faecalibaculum rodentium, Collinsella aerofaciens, and Lactobacillus fermentum and the increase in microbial metabolites, i.e., SCFAs and secondary bile acids, might play a positive role in alleviating MS. Our results suggested that HMF alleviated HFD-induced MS possibly by modulating the composition, function, and metabolism of gut microbiota.PMID:37345674 | DOI:10.1021/acs.jafc.3c01881

New Phytol. 2023 Jun 21. doi: 10.1111/nph.19068. Online ahead of print.ABSTRACTPlants rely on cross-resistance traits to defend against multiple, phylogenetically distinct enemies. These traits are often the result of long co-evolutionary histories. Biological invasions can force naïve plants to cope with novel, coincident pests, and pathogens. For example, European ash (Fraxinus excelsior) is substantially threatened by the emerald ash borer (EAB), Agrilus planipennis, a wood-boring beetle, and the ash dieback (ADB) pathogen, Hymenoscyphus fraxineus. Yet, plant cross-resistance traits against novel enemies are poorly explored and it is unknown whether naïve ash trees can defend against novel enemy complexes via cross-resistance mechanisms. To gain mechanistic insights, we quantified EAB performance on grafted replicates of ash genotypes varying in ADB resistance and characterized ash phloem chemistry with targeted and untargeted metabolomics. Emerald ash borer performed better on ADB-susceptible than on ADB-resistant genotypes. Moreover, changes in EAB performance aligned with differences in phloem chemical profiles between ADB-susceptible and ADB-resistant genotypes. We show that intraspecific variation in phloem chemistry in European ash can confer increased cross-resistance to invasive antagonists from different taxonomic kingdoms. Our study suggests that promotion of ADB-resistant ash genotypes may simultaneously help to control the ADB disease and reduce EAB-caused ash losses, which may be critical for the long-term stability of this keystone tree species.PMID:37345294 | DOI:10.1111/nph.19068

Cancers (Basel). 2023 May 16;15(10):2780. doi: 10.3390/cancers15102780.ABSTRACTBreast cancer has now become the most commonly diagnosed cancer, accounting for one in eight cancer diagnoses worldwide. Non-invasive diagnostic biomarkers and associated tests are superlative candidates to complement or improve current approaches for screening, early diagnosis, or prognosis of breast cancer. Biomarkers detected from body fluids such as blood (serum/plasma), urine, saliva, nipple aspiration fluid, and tears can detect breast cancer at its early stages in a minimally invasive way. The advancements in high-throughput molecular profiling (omics) technologies have opened an unprecedented opportunity for unbiased biomarker detection. However, the irreproducibility of biomarkers and discrepancies of reported markers have remained a major roadblock to clinical implementation, demanding the investigation of contributing factors and the development of standardised biomarker discovery pipelines. A typical biomarker discovery workflow includes pre-analytical, analytical, and post-analytical phases, from sample collection to model development. Variations introduced during these steps impact the data quality and the reproducibility of the findings. Here, we present a comprehensive review of methodological variations in biomarker discovery studies in breast cancer, with a focus on non-nucleotide biomarkers (i.e., proteins, lipids, and metabolites), highlighting the pre-analytical to post-analytical variables, which may affect the accurate identification of biomarkers from body fluids.PMID:37345117 | DOI:10.3390/cancers15102780

Cancers (Basel). 2023 May 10;15(10):2676. doi: 10.3390/cancers15102676.ABSTRACTThe complex molecular alterations that underlie cancer pathophysiology are studied in depth with omics methods using bulk tissue extracts. For spatially resolved tissue diagnostics using needle biopsy cores, however, histopathological analysis using stained FFPE tissue and the immunohistochemistry (IHC) of a few marker proteins is currently the main clinical focus. Today, spatial omics imaging using MSI or IRI is an emerging diagnostic technology for the identification and classification of various cancer types. However, to conserve tissue-specific metabolomic states, fast, reliable, and precise methods for the preparation of fresh-frozen (FF) tissue sections are crucial. Such methods are often incompatible with clinical practice, since spatial metabolomics and the routine histopathology of needle biopsies currently require two biopsies for FF and FFPE sampling, respectively. Therefore, we developed a device and corresponding laboratory and computational workflows for the multimodal spatial omics analysis of fresh-frozen, longitudinally sectioned needle biopsies to accompany standard FFPE histopathology of the same biopsy core. As a proof-of-concept, we analyzed surgical human liver cancer specimens using IRI and MSI with precise co-registration and, following FFPE processing, by sequential clinical pathology analysis of the same biopsy core. This workflow allowed for a spatial comparison between different spectral profiles and alterations in tissue histology, as well as a direct comparison for histological diagnosis without the need for an extra biopsy.PMID:37345020 | DOI:10.3390/cancers15102676

Clin Nutr ESPEN. 2023 Aug;56:83-86. doi: 10.1016/j.clnesp.2023.04.031. Epub 2023 May 5.ABSTRACTINTRODUCTION: Nicotinamide adenine dinucleotide (NAD+) is a coenzyme of the NAD+-dependent protein deacetylase sirtuin-1 (SIRT1). An increase in NAD+ concentration induces SIRT1 activation that results in various health benefits. Since nicotinamide mononucleotide (NMN) is a precursor of NAD+, NMN ingestion is expected to have multiple health benefits such as alleviation of aging, lifestyle-related and neurodegenerative diseases, through the activation of SIRT1. In this study, we aimed to determine the effects of daily NMN ingestion on plasma levels of NMN and NAD+.METHODS: Healthy volunteers received 250 mg of NMN once a day in the morning (n = 11) for 12 weeks, and the plasma concentrations of NMN and NAD+ were measured monthly. Physiological and laboratory tests were performed within 2 h after lunch (at 2 pm) before and during NMN administration.RESULTS: Oral administration of NMN increased the plasma concentrations of NMN and NAD+, and the postprandial serum insulin levels. The elevation levels of NMN and insulin varied widely among individuals. No adverse symptoms were observed in the participants.CONCLUSIONS: Oral administration of NMN elevates plasma levels of NMN and NAD+, and postprandial serum insulin levels.PMID:37344088 | DOI:10.1016/j.clnesp.2023.04.031

J Therm Biol. 2023 May;114:103563. doi: 10.1016/j.jtherbio.2023.103563. Epub 2023 Apr 7.ABSTRACTThermal burn injury is a severe and life-threatening form of trauma that presents a significant challenge to clinical therapy. Therapeutic hypothermia has been shown to be beneficial in various human pathologies. Adenosine triphosphate (ATP) induces a hypothermic state that resembles hibernation-like suspended animation in mammals. This study investigates the potential protective role of ATP-induced hypothermia in thermal burn injury. Male C57BL/6 mice underwent a sham procedure or third-degree burn, and ATP-induced hypothermia was applied immediately or 1 h after burn injury. Our results show that ATP-induced hypothermia significantly improved burn depth progression and reduced collagen degradation. Moreover, hypothermia induced by ATP alleviated burn-induced hyperinflammatory responses and oxidative stress. Metabolomic profiling revealed that ATP-induced hypothermia reversed the shifts of metabolic profiles of the skin in burn mice. In addition, ATP-induced hypothermia relieved nociceptive and inflammatory pain, as observed in the antinociceptive test. Our findings suggest that ATP-induced hypothermia attenuates burn injury and provides new insights into first-aid therapy after thermal burn injury.PMID:37344025 | DOI:10.1016/j.jtherbio.2023.103563

Bioresour Technol. 2023 Jun 19:129366. doi: 10.1016/j.biortech.2023.129366. Online ahead of print.ABSTRACTA bottleneck of microalgae-based techniques for wastewater bioremediation is activity inhibition of microalgae by toxic pollutants. The defense strategies of Chlorella sorokinana against toxic pyridine were studied. Results indicated that pyridine caused photoinhibition and reactive oxygen species overproduction in a concentration-dependent manner. The 50% inhibitory concentration of pyridine (147 mg L-1) destroyed C/N balance, disrupted multiple metabolic pathways of C. sorokinana. In response to pyridine stress, ascorbate peroxidase and catalase activities increased to scavenge reactive oxygen species under pyridine concentrations lower than 23 mg L-1. At higher pyridine concentrations, the activation of calcium signaling pathways and phytohormones represented the predominant defense response. Extracellular polymeric substances increased 3.6-fold in 147 mg L-1 group than control, which interacted with pyridine through hydrophobic and aromatic stacking to resist pyridine entering algal cells. Unraveling the intracellular and extracellular self-defense mechanisms of microalgae against pyridine stress facilitates the development of microalgal-based technology in wastewater bioremediation.PMID:37343803 | DOI:10.1016/j.biortech.2023.129366

Environ Toxicol Pharmacol. 2023 Jun 19:104191. doi: 10.1016/j.etap.2023.104191. Online ahead of print.ABSTRACTCo-exposure of tetracycline (TC) and polyethylene microplastic (MP-PE) pollution might result in more intricate effects on rice growth and grain quality. In present study, two different rice cultivars of contrasting drought tolerance, Hanyou73 (H73, drought-resistant) and Quanyou280 (Q280, drought-sensitive) were grown on MP-PE and TC-contaminated soils under drought. It was found that drought stress had different influence on TC accumulation in the two rice cultivars. H73 accumulated more TC in leaves and grains without drought stress while Q280 accumulated more TC under drought stress. Furthermore, metabolomics results demonstrated that under drought stress, about 80% of metabolites in H73 and 95% in Q280 were down-regulated as compared to non-drought treatments. These findings provide insights into the effects of TC and MP-PE with and without drought stress on potential risks to rice growth and grain quality, which has implications on rice production and cultivar election under multiple-stress conditions.PMID:37343773 | DOI:10.1016/j.etap.2023.104191

Ageing Res Rev. 2023 Jun 19:101987. doi: 10.1016/j.arr.2023.101987. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is determined by various pathophysiological mechanisms starting 10 to 25 years before the onset of clinical symptoms. As multiple functionally interconnected molecular/cellular pathways appear disrupted in AD, the exploitation of high-throughput unbiased omics sciences is critical to elucidating the precise pathogenesis of AD. Among different omics, metabolomics is a fast-growing discipline allowing for the simultaneous detection and quantification of hundreds/thousands of perturbed metabolites in tissues or biofluids, reproducing the fluctuations of multiple networks affected by a disease. Here, we seek to critically depict the main metabolomics methodologies with the aim of identifying new potential AD biomarkers and further elucidating AD pathophysiological mechanisms. From a systems biology perspective, as metabolic alterations can occur before the development of clinical signs, metabolomics - coupled with existing accessible biomarkers used for AD screening and diagnosis - can support early disease diagnosis and help develop individualized treatment plans. Presently, the majority of metabolomic analyses emphasized that lipid metabolism is the most consistently altered pathway in AD pathogenesis. The possibility that metabolomics may reveal crucial steps in AD pathogenesis is undermined by the difficulty in discriminating between the causal or epiphenomenal or compensatory nature of metabolic findings.PMID:37343679 | DOI:10.1016/j.arr.2023.101987