PubMed

J Pharm Anal. 2023 Oct;13(10):1195-1204. doi: 10.1016/j.jpha.2023.04.005. Epub 2023 Apr 12.ABSTRACTIn vivo lung perfusion (IVLP) is a novel isolated lung technique developed to enable the local, in situ administration of high-dose chemotherapy to treat metastatic lung cancer. Combination therapy using folinic acid (FOL), 5-fluorouracil (F), and oxaliplatin (OX) (FOLFOX) is routinely employed to treat several types of solid tumours in various tissues. However, F is characterized by large interpatient variability with respect to plasma concentration, which necessitates close monitoring during treatments using of this compound. Since plasma drug concentrations often do not reflect tissue drug concentrations, it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs. In this work, in vivo solid-phase microextraction (in vivo SPME) is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous (IV) trials. The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration (IVLP vs. IV) and the therapy itself. This study also shows that the immediate instrumental analysis of metabolomic samples is ideal, as long-term storage at -80 °C results in changes in the metabolite content in the sample extracts.PMID:38024854 | PMC:PMC10657970 | DOI:10.1016/j.jpha.2023.04.005

Drug Des Devel Ther. 2023 Nov 15;17:3409-3428. doi: 10.2147/DDDT.S427837. eCollection 2023.ABSTRACTPURPOSE: Compound Anoectochilus roxburghii (Wall.) Lindl oral liquid (CAROL) is often as a hepatoprotective agent. The present study aimed to elucidate the protective mechanism of CAROL against alcoholic liver injury in rats by untargeted metabolomics combined with multivariate statistical analysis.METHODS: An alcoholic liver disease model was established in sprague-dawley (SD) rats by gavage of alcohol, and CAROL treatment was administered. The hepatoprotective effect of CAROL was evaluated by examining liver tissues changes and detecting biochemical index activities and cytokines in serum and liver homogenates. The metabolites in serum samples were examined using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) and multivariate statistical analysis to screen for differentially expressed metabolites and Kyoto Encyclopedia of Genes and Genomes (KEGG) to assess potential metabolic pathways.RESULTS: CAROL has the potential to downregulate inflammation levels and alleviate oxidative stress. The differential metabolites are mainly engaged in riboflavin metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis metabolism, phenylalanine metabolism, pyrimidine metabolism, and vitamin B6 metabolism to achieve hepatoprotective effects.CONCLUSION: CAROL may exhibit beneficial hepatoprotective effects by reducing inflammation, mitigating oxidative stress, and modulating metabolites and their metabolic pathways.This study has important implications for advancing the clinical application of CAROL.PMID:38024538 | PMC:PMC10659148 | DOI:10.2147/DDDT.S427837

Aquac Nutr. 2023 Nov 16;2023:9775823. doi: 10.1155/2023/9775823. eCollection 2023.ABSTRACTAlkalinity stress is the main stress experienced by aquatic animals in saline-alkali water, which hinders the aquaculture development and the utilization of water resources. The two-factor (2 × 3) test was adopted to study the influence of dietary protein to carbohydrate ratios on the energy metabolism of Nile tilapia (Oreochromis niloticus) under different alkalinity stress levels. Three diets with different protein-carbohydrate ratios (P27/C35, P35/C25, and P42/C15) were fed to fish cultured in freshwater (FW, 1.3 mmol/L carbonate alkalinity) or alkaline water (AW, 35.7 mmol/L carbonate alkalinity) for 50 days. Ambient alkalinity decreased tilapia growth performance. Although ambient alkalinity caused oxidative stress and enhanced ion transport and ammonia metabolism in tilapia, tilapia fed the P27/C35 diet showed better adaptability than fish fed the other two diets in alkaline water. Further metabolomic analysis showed that tilapia upregulated all the pathways enriched in this study to cope with alkalinity stress. Under alkalinity stress, tilapia fed the P27/C35 diet exhibited enhanced pyruvate metabolism and purine metabolism compared with tilapia fed the P42/C15 diet. This study indicated that ambient alkalinity could significantly decrease growth performance and cause oxidative stress and osmotic regulation. However, reducing dietary protein content by increasing carbohydrates could weaken stress and improve growth performance, ion transport, and ammonia metabolism in tilapia under long-term hyperalkaline exposure.PMID:38023982 | PMC:PMC10667043 | DOI:10.1155/2023/9775823

Front Plant Sci. 2023 Nov 3;14:1268014. doi: 10.3389/fpls.2023.1268014. eCollection 2023.ABSTRACTClimate change is considered a serious threat to agriculture and food security. It is linked to rising temperatures and water shortages, conditions that are expected to worsen in the coming decades. Consequently, the introduction of more drought-tolerant crops is required. Quinoa (Chenopodium quinoa Willd.) has received great attention worldwide due to the nutritional properties of its seeds and its tolerance to abiotic stress. In this work, the agronomic performance and seed nutritional quality of three quinoa varieties were studied during two consecutive years (2019-2020) under three water environmental conditions of Southwestern Europe (irrigated conditions, fresh rainfed, and hard rainfed) with the goal of determining the impact of rainfed conditions on this crop performance. High precipitations were recorded during the 2020 growing season resulting in similar grain yield under irrigation and fresh rainfed conditions. However, in 2019, significant yield differences with penalties under water-limiting conditions were found among the evaluated environmental conditions. Furthermore, nutritional and metabolomic differences were observed among seeds harvested from different water environments including the progressive accumulation of glycine betaine accompanied by an increase in saponin and a decrease in iron with water limitation. Generally, water-limiting environments were associated with increased protein contents and decreased yields preserving a high nutritional quality despite particular changes. Overall, this work contributes to gaining further knowledge about how water availability affects quinoa field performance, as it might impact both seed yield and quality. It also can help reevaluate rainfed agriculture, as water deficit can positively impact the nutritional quality of seeds.PMID:38023922 | PMC:PMC10662129 | DOI:10.3389/fpls.2023.1268014

Front Plant Sci. 2023 Nov 2;14:1218984. doi: 10.3389/fpls.2023.1218984. eCollection 2023.ABSTRACTRocket (Eruca vesicaria subsp. sativa) is a source of sulfur-containing glucosinolates (GSLs). GSLs and their breakdown hydrolysis products (GHPs) are responsible for health-related benefits, such as anti-cancer and anti-neurodegenerative properties. Understanding how phytochemical composition changes between cultivation environments is key to developing cultivars with improved nutritional quality. Two consecutive harvests (first and second regrowth) of crops, grown in both Italy and the UK, were used to determine the phytochemical and transcriptomic differences between six lines of Eruca. Samples were taken upon delivery from field sites (D0) and after five days of cold storage (D5) for each location. Leaves were analysed for sulfur content, volatile organic compounds (VOCs), GSLs, GHPs, and sugars. Transcriptome data were associated with metabolite profiles to identify differentially expressed genes between plants grown in the two environments. VOC compounds (carbon disulfide, methyl thiocyanate) were associated with growth environment and with differences in sulfur metabolism gene expression (APR2, LSU2, LSU3, SDI1, SiR), GSL biosynthesis (MYB28, FMOGS-OX2) and GHP formation (ESM1, TGG1, TGG2). The concentrations of sugars were an order of magnitude greater in UK grown samples (up to 29.9 mg g-1 dry weight; dw). Sulfur content was significantly higher in the Italy plant samples (11.4 - 20.1 mg g-1 dw), which was in turn associated with higher concentrations of GSLs (pentyl GSL, up to 15.8 μmol g-1 dw; sinigrin, up to 0.005 μmol g-1 dw; glucoraphanin, up to 5.1 μmol g-1 dw; glucorucolamine, up to 23.6 μmol g-1 dw; neoglucobrassicin, up to 5.3 μmol g-1 dw) and hydrolysis products (sativin, up to 13.5 μmol g-1 dw; erucin, up to 1 μmol g-1 dw; sulforaphane, up to 34.7 μmol g-1 dw). VOC profiles of plants cultivated in the UK were distinct from Italy grown plants, with higher relative abundances of alkanes and esters in second cut and shelf-life (D5) samples. The data indicate a significant interaction of cultivar response with environment, highlighting the difficulty of producing Eruca crops with consistent phytochemical and postharvest traits. Genes with differential expression between plants grown in Italy and the UK could be used as markers of phytochemical quality and composition.PMID:38023917 | PMC:PMC10652768 | DOI:10.3389/fpls.2023.1218984

Front Plant Sci. 2023 Nov 8;14:1327345. doi: 10.3389/fpls.2023.1327345. eCollection 2023.NO ABSTRACTPMID:38023911 | PMC:PMC10663318 | DOI:10.3389/fpls.2023.1327345

Front Plant Sci. 2023 Nov 7;14:1256091. doi: 10.3389/fpls.2023.1256091. eCollection 2023.ABSTRACTSince ancient times, Azadirachta indica, or Neem, has been a well-known species of plant that produces a broad range of bioactive terpenoid chemicals that are involved in a variety of biological functions. Understanding the molecular mechanisms that are responsible for the biosynthesis and control of terpenoid synthesis is majorly dependent on successfully identifying the genes that are involved in their production. This review provides an overview of the recent developments concerning the identification of genes in A. indica that are responsible for the production of terpenoids. Numerous candidate genes encoding enzymes that are involved in the terpenoid biosynthesis pathway have been found through the use of transcriptomic and genomic techniques. These candidate genes include those that are responsible for the precursor synthesis, cyclization, and modification of terpenoid molecules. In addition, cutting-edge omics technologies, such as metabolomics and proteomics, have helped to shed light on the intricate regulatory networks that govern terpenoid biosynthesis. These networks are responsible for the production of terpenoids. The identification and characterization of genes involved in terpenoid biosynthesis in A. indica presents potential opportunities for genetic engineering and metabolic engineering strategies targeted at boosting terpenoid production as well as discovering novel bioactive chemicals.PMID:38023910 | PMC:PMC10664250 | DOI:10.3389/fpls.2023.1256091

J Immunol. 2023 Nov 29:ji2300319. doi: 10.4049/jimmunol.2300319. Online ahead of print.ABSTRACTImmune cell-derived IL-17A is one of the key pathogenic cytokines in psoriasis, an immunometabolic disorder. Although IL-17A is an established regulator of cutaneous immune cell biology, its functional and metabolic effects on nonimmune cells of the skin, particularly keratinocytes, have not been comprehensively explored. Using multiomics profiling and systems biology-based approaches, we systematically uncover significant roles for IL-17A in the metabolic reprogramming of human primary keratinocytes (HPKs). High-throughput liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy revealed IL-17A-dependent regulation of multiple HPK proteins and metabolites of carbohydrate and lipid metabolism. Systems-level MitoCore modeling using flux-balance analysis identified IL-17A-mediated increases in HPK glycolysis, glutaminolysis, and lipid uptake, which were validated using biochemical cell-based assays and stable isotope-resolved metabolomics. IL-17A treatment triggered downstream mitochondrial reactive oxygen species and HIF1α expression and resultant HPK proliferation, consistent with the observed elevation of these downstream effectors in the epidermis of patients with psoriasis. Pharmacological inhibition of HIF1α or reactive oxygen species reversed IL-17A-mediated glycolysis, glutaminolysis, lipid uptake, and HPK hyperproliferation. These results identify keratinocytes as important target cells of IL-17A and reveal its involvement in multiple downstream metabolic reprogramming pathways in human skin.PMID:38019129 | DOI:10.4049/jimmunol.2300319

J Immunol. 2023 Nov 29:ji2300090. doi: 10.4049/jimmunol.2300090. Online ahead of print.ABSTRACTSalmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm-infected C57BL6/J mice were used to demonstrate the therapeutic benefits of the Bacillus velezensis JT3-1 (B. velezensis/JT3-1) strain or its cell-free supernatant in enhancing Trp metabolism. Targeted Trp metabolomic analyses indicated the predominance of indole-3-lactic acid (ILA), an indole derivative and ligand for aryl hydrocarbon receptor (AHR). Based on the 16S amplicon sequencing and correlation analysis of metabolites, we found that B. velezensis supported the relative abundance of Lactobacillus and Ligilactobacillus in mouse gut and showed positive correlations with ILA levels. Moreover, AHR and its downstream genes (especially IL-22) significantly increased in mouse colons after B. velezensis or cell-free supernatant treatment, suggesting the importance of AHR pathway activation. In addition, ILA was found to stimulate primary mouse macrophages to secrete IL-22, which was antagonized by CH-223191. Furthermore, ILA could protect mice from S. Tm infection by increasing IL-22 in Ahr+/- mice, but not in Ahr-/- mice. Finally, Trp-rich feeding showed amelioration of S. Tm infection in mice, and the effect depended on gut microbiota. Taken together, these results suggest that B. velezensis-associated ILA contributes to protecting mice against S. Tm infection by activating the AHR/IL-22 pathway. This study provides insights into the involvement of microbiota-derived Trp catabolites in protecting against Salmonella infection.PMID:38019127 | DOI:10.4049/jimmunol.2300090

mSystems. 2023 Nov 29:e0084423. doi: 10.1128/msystems.00844-23. Online ahead of print.ABSTRACTThe improvement of chicken growth performance is one of the major concerns for the poultry industry. Gut microbes are increasingly evidenced to be associated with chicken physiology and metabolism, thereby influencing chicken growth and development. Here, through integrated multi-omics analyses, we showed that chickens from the same line differing in their body weight were very different in their gut microbiota structure and host-microbiota crosstalk; microbes in high body weight (HBW) chickens contributed to chicken growth by regulating the gut function and homeostasis. We also verified that a specific bacterial consortium consisting of isolates from the HBW chickens has the potential to be used as chicken growth promoters. These findings provide new insights into the potential links between gut microbiota and chicken phenotypes, shedding light on future manipulation of chicken gut microbiota to improve chicken growth performance.PMID:38018992 | DOI:10.1128/msystems.00844-23

J Proteome Res. 2023 Nov 29. doi: 10.1021/acs.jproteome.3c00105. Online ahead of print.ABSTRACTThe purpose of this study was to determine potential metabolic biomarkers and therapeutic drugs in the gingival tissue of individuals with periodontitis. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the gingival tissue samples from 20 patients with severe periodontitis and 20 healthy controls. Differential metabolites were identified using variable important in projection (VIP) values from the orthogonal partial least squares discrimination analysis (OPLS-DA) model and then verified for significance between groups using a two-tailed Student's t test. In total, 65 metabolites were enriched in 33 metabolic pathways, with 40 showing a significant increase and 25 expressing a significant decrease. In addition, it was found that patients with severe periodontitis have abnormalities in metabolic pathways, such as glucose metabolism, purine metabolism, amino acid metabolism, and so on. Furthermore, based on a multidimensional analysis, 12 different metabolites may be the potential biomarkers of severe periodontitis. The experiment's raw data have been uploaded to the MetaboLights database, and the project number is MTBLS8357. Moreover, osteogenesis differentiation characteristics were detected in the selected metabolites. The findings may provide a basis for the study of diagnostic biomarkers and therapeutic metabolites in severe periodontitis.PMID:38018860 | DOI:10.1021/acs.jproteome.3c00105

J Proteome Res. 2023 Nov 29. doi: 10.1021/acs.jproteome.3c00443. Online ahead of print.ABSTRACTDuring demyelination, lipid-rich myelin debris is released in the central nervous system (CNS) and must be phagocytosed and processed before new myelin can form. Although myelin comprises over 70% lipids, relatively little is known about how the CNS lipidome changes during demyelination and remyelination. In this study, we obtained a longitudinal lipidomic profile of the brain, spinal cord, and serum using a genetic mouse model of demyelination, known as Plp1-iCKO-Myrf. The mass spectrometry data is available at the Metabolomics Workbench, where it has been assigned Study ID ST002958. This model has distinct phases of demyelination and remyelination over the course of 24 weeks, in which loss of motor function peaks during demyelination. Using principal component analysis (PCA) and volcano plots, we have demonstrated that the brain and spinal cord have different remyelination capabilities and that this is reflected in different lipidomic profiles over time. We observed that plasmalogens (ether-linked phosphatidylserine and ether-linked phosphatidylcholine) were elevated specifically during the early stages of active demyelination. In addition, we identified lipids in the brain that were altered when mice were treated with a remyelinating drug, which may be CNS biomarkers of remyelination. The results of this study provide new insights into how the lipidome changes in response to demyelination, which will enable future studies to elucidate mechanisms of lipid regulation during demyelination and remyelination.PMID:38018851 | DOI:10.1021/acs.jproteome.3c00443

Immun Inflamm Dis. 2023 Nov;11(11):e1088. doi: 10.1002/iid3.1088.ABSTRACTBACKGROUND: Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia.OBJECTIVE: This study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan-Kynurenine pathway and the severity of severe pneumonia, as well as N-3/N-6 polyunsaturated fatty acids (PUFAs).METHODS: In this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups.RESULTS: Metabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (linolenic acid, α-LNA), arachidonic acid (ARA), Dihomo-γ-linolenic acid (DGLA), and 13(s)-hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)-hydroxyeicosatetraenoic acid (HETE), 11(S)-HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)-hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α-LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)-HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α-LNA, DHA, and DPA.CONCLUSION: This study revealed that during severe pneumonia, the Tryptophan-Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan-Kynurenine pathway was negatively correlated with N-3/N-6 PUFAs.PMID:38018595 | DOI:10.1002/iid3.1088

Circulation. 2023 Nov 29. doi: 10.1161/CIRCULATIONAHA.123.066110. Online ahead of print.ABSTRACTBACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular condition, but approved medical therapies to prevent AAA progression and rupture are currently lacking. Sphingolipid metabolism disorders are associated with the occurrence and development of AAA. It has been discovered that ganglioside GM3, a sialic acid-containing type of glycosphingolipid, plays a protective role in atherosclerosis, which is an important risk factor for AAA; however, the potential contribution of GM3 to AAA development has not been investigated.METHODS: We performed a metabolomics study to evaluated GM3 level in plasma of human patients with AAA. We profiled GM3 synthase (ST3GAL5) expression in the mouse model of aneurysm and human AAA tissues through Western blotting and immunofluorescence staining. RNA sequencing, affinity purification and mass spectrometry, proteomic analysis, surface plasmon resonance analysis, and functional studies were used to dissect the molecular mechanism of GM3-regulating ferroptosis. We conditionally deleted and overexpressed St3gal5 in smooth muscle cells (SMCs) in vivo to investigate its role in AAA.RESULTS: We found significantly reduced plasma levels of GM3 in human patients with AAA. GM3 content and ST3GAL5 expression were decreased in abdominal aortic vascular SMCs in patients with AAA and an AAA mouse model. RNA sequencing analysis showed that ST3GAL5 silencing in human aortic SMCs induced ferroptosis. We showed that GM3 interacted directly with the extracellular domain of TFR1 (transferrin receptor 1), a cell membrane protein critical for cellular iron uptake, and disrupted its interaction with holo-transferrin. SMC-specific St3gal5 knockout exacerbated iron accumulation at lesion sites and significantly promoted AAA development in mice, whereas GM3 supplementation suppressed lipid peroxidation, reduced iron deposition in aortic vascular SMCs, and markedly decreased AAA incidence.CONCLUSIONS: Together, these results suggest that GM3 dysregulation promotes ferroptosis of vascular SMCs in AAA. Furthermore, GM3 may constitute a new therapeutic target for AAA.PMID:38018467 | DOI:10.1161/CIRCULATIONAHA.123.066110

J Sci Food Agric. 2023 Nov 29. doi: 10.1002/jsfa.13139. Online ahead of print.ABSTRACTBACKGROUND: Extra Virgin Olive oil (EVOO), a natural product with a multidiscipline role has been and is continuing to be studied from several points of view. Among them, its chemical analysis is of major importance and several methods have been used. NMR spectroscopy bears its inherent advantages, among them monitoring the chemical constituents without the need of a separation technique and without for instance possible carry over effects. Additionally, several magnetic resonance spectroscopy techniques can provide a novel powered insight in the nature and the properties of a sample under study. Moreover, -omics procedure can reveal new information and can lead to the classification of populations under study. The main objective of the present work was the possible classification of the EVOO samples based on their aldehyde content using a proposed unreferenced 1 H NMR spectroscopic quantification method combined with a metabolomic approach. Moreover, the study of the impact of such elevated aldehyde content to several spectra regions of importance in the proton NMR spectra, along with the proposal of a new isomer - possible indicator.RESULTS: Univariate analysis of twelve EVOO samples showed that oleacein, oleocanthal, elenolic acid, the hydroxytyrosol / hydroxytyrosol derivatives and tyrosol / tyrosol derivatives, strongly differentiate the two classes of EVOO: the OEH (for high aldehyde EVOO content) and the OE (for non-high aldehyde content). Moreover, we pointed out the "impact" of such elevated secoiridoid and derivatives' content, through their moieties' units, on a range of several resonances of the 1 H NMR spectrum. The metabolomic approach, showed the classification of EVOO samples based on their secoiridoid and their derivatives' content. Multivariate analysis showed a strong influence on the discrimination of the EVOO classes based on the protons resonating at the aldehyde region of the 1 H NMR spectrum; the aldehyde protons that correspond to 5S,4R-ligstrodial and 5S,4R-oleuropeindial, oleacein, oleocanthal, elenolic acid, p-HPEA-EA, 3,4-DHPEA-EA, 5S,4R- and 5S,4S- ligstrodial and the proton that correspond to a new compound that is reported for the first time. This isomer compound, reported for the first time, could serve as a possible indicator for the EVOO classification.CONCLUSIONS: An unreferenced quantification method was proposed and EVOO samples were classified into two classes: OEH and OE according to their aldehyde content gaining thus probably higher nutrient and possible pharmacological value. Moreover, we point out the "impact" of such elevated aldehyde content on several spectral regions of the 1 H spectrum. Finally, a new compound was detected in the OEH samples and is reported for the first time. This compound could possibly be an indicator. This article is protected by copyright. All rights reserved.PMID:38018400 | DOI:10.1002/jsfa.13139

J Cachexia Sarcopenia Muscle. 2023 Nov 28. doi: 10.1002/jcsm.13379. Online ahead of print.ABSTRACTBACKGROUND: Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness.METHODS: In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored.RESULTS: Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO-1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF-κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels.CONCLUSIONS: Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-κB-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.PMID:38018317 | DOI:10.1002/jcsm.13379

J Sci Food Agric. 2023 Nov 28. doi: 10.1002/jsfa.13180. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary fibrosis (PF) is the terminal manifestation of a type of pulmonary disease, which seriously affected the respiratory function of body, and with no effective cure for treatment. This study evaluated the effect of sea cucumber peptides (SCP) on bleomycin (BLM)-induced SD rat pulmonary fibrosis.RESULTS: SCP can inhibit the PF induced by bleomycin. PF and SCP did not affect the food intake of rats, but PF reduced the body weight of rats, and SCP could improve the weight loss. SCP reduced lung index in PF rats in a dose-dependent manner. The SCP significantly reduced IL-1β, IL-6, TNF-α, α-SMA and VIM expression levels in lung tissue (P < 0.05), significantly decreased TGF-β1 expression level in serum (P < 0.01), and the LSCP group and MSCP group had better inhibitory effects on PF than HSCP group. Histomorphological results showed that SCP could ameliorate the structural damage of lung tissue, alveolar wall rupture, inflammatory cell infiltration, fibroblast proliferation, and deposition of intercellular matrix and collagen fibers caused by PF. The improvement effect of MSCP group was the most noteworthy in histomorphology. Metabolomics results showed that SCP significantly down-regulated catechol, N-acetyl-L-histidine, acetylcarnitine, stearoylcarnitine, D-mannose, L-threonine, L-Alanine, glycine, 3-guanidinopropionic acid, prostaglandin D2 and embelic acid D (-)-β-hydroxybutyric acid expression levels in lung tissue.CONCLUSION: SCP ameliorate the BLM-induced SD rat pulmonary fibrosis. The KEEG pathway analysis proved that SCP intervened in PF mainly via the lysosome pathway, with D-mannose as the key factor. This article is protected by copyright. All rights reserved.PMID:38018265 | DOI:10.1002/jsfa.13180

Curr Med Chem. 2023 Nov 24. doi: 10.2174/0109298673257429231108072717. Online ahead of print.ABSTRACTBACKGROUND: Chemoresistance by stemness in HPV-induced cervical carcinogenesis has significant implications for the overall disease-specific survival of the patients. To date, there are no reports related to the implications of significant aspects of inflammation and microbiome-- mediated epigenetics in cervical cancers.OBJECTIVE: The current systematic review delineates the significant aspects of the inflammation-related pathophysiology, cervical cancer diagnosis based on the HPV-indued stemness, and microbiome- mediated epigenetic markers to develop personalized therapies to target the stemness-acquired indefinitely dividing cancer stem cells.METHODS: We performed a systematic review without a meta- analysis. We searched several public databases, such as Pubmed, ReleMed, National Library of Medicine, and Scopus, related to inflammation, metabolomics, microbiome-mediated epigenetic markers, and HPV-induced stemness.RESULTS AND CONCLUSION: The review significantly described the correlation between microbial inflammation and stem cell stochasticity of HPV-Induced cervical cancer and the expression of epigenetics- based biomarkers through microbiome and metabolome to foster the cervical cancer progression. These are major risk factors that can cause cervical dysplasia with substantial therapy resistance in cervical cancer patients. The qualitative and quantitative examination of the spatial transcriptomic expression of these stemness markers in the dividing cervical cancer stem cells has significant implications in the clinical sector to develop early personalized medicine to prevent cervical precancerous lesions depending on the prognosis of the cervical cancer patients. Mainly, the combinatorial regimen of current therapeutic modalities, along with microbiome-related therapies with future landscape of epigenetics-modulated therapies, may enhance overall disease-specific survival by modulating the stochastic dynamics of basal epithelial cells across the cervical region.PMID:38018189 | DOI:10.2174/0109298673257429231108072717

Anal Chem. 2023 Nov 28. doi: 10.1021/acs.analchem.3c01731. Online ahead of print.ABSTRACTAmino acids (AAs), which are low-molecular-weight (low-MW) metabolites, serve as essential building blocks not only for protein synthesis but also for maintaining the nitrogen balance in living systems. In situ detection and imaging of AAs are crucial for understanding more complex biological processes. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a label-free mass spectrometric imaging technique that enables the simultaneous detection and imaging of the spatial distribution and relative abundance of different endogenous/exogenous compounds in biological samples. The excellent efficiency of MALDI-MSI is attributed to the choice of the MALDI matrix. However, to the best of our knowledge, no matrix has been specifically developed for AAs. Herein, we report a MALDI matrix, 2,5-dihydroxyterephthalic acid (DHT), which can improve the detection and imaging of AAs in biological samples by MALDI-MS. Our results indicated that DHT exhibited strong ultraviolet-visible (UV-vis) absorption, uniform matrix deposition, and high vacuum stability. Moreover, the matrix-related ion signals produced from DHT were reduced by 50 and 71.8% at m/z < 500 compared to the commonly used matrices of 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA), respectively, in their respective organic solvents. In terms of quantitative performance, arginine, glutamic acid, glutamine, and proline can be detected with limits of detection of 6, 4, 6, and 4 ng/mL, respectively, using the DHT as the matrix. Using DHT as the matrix, all 20 protein AAs were successfully detected in human serum by MALDI-MS, whereas only 7 and 10 AAs were detected when DHB and CHCA matrices were used, respectively. Furthermore, 20 protein AAs and taurine were successfully detected and imaged in a section of edible Crassostrea gigas (oyster) tissue for the first time. Our study demonstrates that using DHT as a matrix can improve the detection and imaging of AAs in biological samples by MALDI-MS.PMID:38018128 | DOI:10.1021/acs.analchem.3c01731

Addict Biol. 2023 Dec;28(12):e13352. doi: 10.1111/adb.13352.ABSTRACTAs a chewing hobby, areca nut (Areca catechu L.) has become the most common psychoactive substance in the world, besides tobacco, alcohol and caffeinated beverages. Moreover, as a first-class carcinogen designated by International Agency for Research on Cancer, long-term chewing areca nut can result in oral mucosal diseases and even oral cancer. To clarify the potential mechanism of areca nut addiction, an integrated strategy of metabolomics and network pharmacology was adopted in this study. Network pharmacology study indicated that all the key targets related to areca nut addiction could be regulated by arecoline and pointed out the importance of G-protein coupled receptor signalling pathway. Analysis results of mice plasma metabolome and faeces metabolome intervened by arecoline suggested that the component may affect the dopamine system and 5-HT system by regulating phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism and intestinal flora structure. Moreover, the potential importance of bile acids in formation of addictive behaviour of chewing areca nut was investigated by integrative analysis of the relationships between metabolites and intestinal flora. The study can provide scientific basis for the addiction intervention and treatment of areca nut chewers.PMID:38017647 | DOI:10.1111/adb.13352