PubMed

Int J Mol Sci. 2023 Sep 21;24(18):14362. doi: 10.3390/ijms241814362.ABSTRACTIn this narrative review, we aim to point out the close relationship between mpox virus (MPXV) infection and the role of saliva as a diagnostic tool for mpox, considering the current molecular approach and in the perspective of OMICs application. The MPXV uses the host cell's rough endoplasmic reticulum, ribosomes, and cytoplasmic proteins to replicate its genome and synthesize virions for cellular exit. The presence of oral mucosa lesions associated with mpox infection is one of the first signs of infection; however, current diagnostic tools find it difficult to detect the virus before the rashes begin. MPXV transmission occurs through direct contact with an infected lesion and infected body fluids, including saliva, presenting a potential use of this fluid for diagnostic purposes. Currently available diagnostic tests for MPXV detection are performed either by real-time quantitative PCR (RT-qPCR) or ELISA, which presents several limitations since they are invasive tests. Despite current clinical trials with restricted sample size, MPXV DNA was detected in saliva with a sensitivity of 85%-100%. In this context, the application of transcriptomics, metabolomics, lipidomics, or proteomics analyses coupled with saliva can identify novel disease biomarkers. Thus, it is important to note that the identification and quantification of salivary DNA, RNA, lipid, protein, and metabolite can provide novel non-invasive biomarkers through the use of OMICs platforms aiding in the early detection and diagnosis of MPXV infection. Untargeted mass spectrometry (MS)-based proteomics reveals that some proteins also expressed in saliva were detected with greater expression differences in blood plasma when comparing mpox patients and healthy subjects, suggesting a promising alternative to be applied in screening or diagnostic platforms for mpox salivary diagnostics coupled to OMICs.PMID:37762664 | DOI:10.3390/ijms241814362

Int J Mol Sci. 2023 Sep 20;24(18):14309. doi: 10.3390/ijms241814309.ABSTRACTAluminum (Al) toxicity is a major limiting factor for plant growth and crop production in acidic soils. This study aims to investigate the effects of γ-aminobutyric acid (GABA) priming on mitigating acid-Al toxicity to creeping bentgrass (Agrostis stolonifera) associated with changes in plant growth, photosynthetic parameters, antioxidant defense, key metabolites, and genes related to organic acids metabolism. Thirty-seven-old plants were primed with or without 0.5 mM GABA for three days and then subjected to acid-Al stress (5 mmol/L AlCl3·6H2O, pH 4.35) for fifteen days. The results showed that acid-Al stress significantly increased the accumulation of Al and also restricted aboveground and underground growths, photosynthesis, photochemical efficiency, and osmotic balance, which could be effectively alleviated by GABA priming. The application of GABA significantly activated antioxidant enzymes, including superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, to reduce oxidative damage to cells under acid-Al stress. Metabolomics analysis demonstrated that the GABA pretreatment significantly induced the accumulation of many metabolites such as quinic acid, pyruvic acid, shikimic acid, glycine, threonine, erythrose, glucose-6-phosphate, galactose, kestose, threitol, ribitol, glycerol, putrescine, galactinol, and myo-inositol associated with osmotic, antioxidant, and metabolic homeostases under acid-Al stress. In addition, the GABA priming significantly up-regulated genes related to the transportation of malic acid and citric acid in leaves in response to acid-Al stress. Current findings indicated GABA-induced tolerance to acid-Al stress in relation to scavenging of reactive oxygen species, osmotic adjustment, and accumulation and transport of organic metabolites in leaves. Exogenous GABA priming could improve the phytoremediation potential of perennial creeping bentgrass for the restoration of Al-contaminated soils.PMID:37762612 | DOI:10.3390/ijms241814309

Int J Mol Sci. 2023 Sep 18;24(18):14230. doi: 10.3390/ijms241814230.ABSTRACTSoybean (Glycine max) is an important crop, rich in proteins, vegetable oils and several other phytochemicals, which is often affected by light during growth. However, the specific regulatory mechanisms of leaf development under shade conditions have yet to be understood. In this study, the transcriptome and metabolome sequencing of leaves from the shade-tolerant soybean 'Nanxiadou 25' under natural light (ND1) and 50% shade rate (SHND1) were carried out, respectively. A total of 265 differentially expressed genes (DEGs) were identified, including 144 down-regulated and 121 up-regulated genes. Meanwhile, KEGG enrichment analysis of DEGs was performed and 22 DEGs were significantly enriched in the top five pathways, including histidine metabolism, riboflavin metabolism, vitamin B6 metabolism, glycerolipid metabolism and cutin, suberine and wax biosynthesis. Among all the enrichment pathways, the most DEGs were enriched in plant hormone signaling pathways with 19 DEGs being enriched. Transcription factors were screened out and 34 differentially expressed TFs (DETFs) were identified. Weighted gene co-expression network analysis (WGCNA) was performed and identified 10 core hub genes. Combined analysis of transcriptome and metabolome screened out 36 DEGs, and 12 potential candidate genes were screened out and validated by quantitative real-time polymerase chain reaction (qRT-PCR) assay, which may be related to the mechanism of shade tolerance in soybean, such as ATP phosphoribosyl transferase (ATP-PRT2), phosphocholine phosphatase (PEPC), AUXIN-RESPONSIVE PROTEIN (IAA17), PURPLE ACID PHOSPHATASE (PAP), etc. Our results provide new knowledge for the identification and function of candidate genes regulating soybean shade tolerance and provide valuable resources for the genetic dissection of soybean shade tolerance molecular breeding.PMID:37762532 | DOI:10.3390/ijms241814230

Int J Mol Sci. 2023 Sep 18;24(18):14206. doi: 10.3390/ijms241814206.ABSTRACTAlkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.PMID:37762509 | DOI:10.3390/ijms241814206

Int J Mol Sci. 2023 Sep 14;24(18):14086. doi: 10.3390/ijms241814086.ABSTRACTRoot-soil underground interactions mediated by soil microorganisms and metabolites are crucial for fertilizer utilization efficiency and crop growth regulation. This study employed a combined approach of soil microbial community profiling and non-targeted metabolomics to investigate the patterns of root-associated microbial aggregation and the mechanisms associated with metabolites under varying controlled-release fertilizer (CRF) application rates. The experimental treatments included five field application rates of CRF (D1: 675 kg/ha; D15: 1012.5 kg/ha; D2: 1350 kg/ha; D25: 1687.5 kg/ha; and D3: 2025 kg/ha) along with traditional fertilizer as a control (CK: 1687.5 kg/ha). The results indicated that the growth of sugarcane in the field was significantly influenced by the CRF application rate (p < 0.05). Compared with CK, the optimal field application of CRF was observed at D25, resulting in a 16.3% to 53.6% increase in sugarcane yield. Under the condition of reducing fertilizer application by 20%, D2 showed a 13.3% increase in stem yield and a 6.7% increase in sugar production. The bacterial ACE index exhibited significant differences between D25 and D1, while the Chao1 index showed significance among the D25, D1, and CK treatments. The dominant bacterial phyla in sugarcane rhizosphere aggregation included Proteobacteria, Actinobacteriota, and Acidobacteriota. Fungal phyla comprised Rozellomycota, Basidiomycota, and Ascomycota. The annotated metabolic pathways encompassed biosynthesis of secondary metabolites, carbohydrate metabolism, and lipid metabolism. Differential analysis and random forest selection identified distinctive biomarkers including Leotiomycetes, Cercospora, Anaeromyxobacter, isoleucyl-proline, and methylmalonic acid. Redundancy analysis unveiled soil pH, soil organic carbon, and available nitrogen as the primary drivers of microbial communities, while the metabolic profiles were notably influenced by the available potassium and phosphorus. The correlation heatmaps illustrated potential microbial-metabolite regulatory mechanisms under CRF application conditions. These findings underscore the significant potential of CRF in sugarcane field production, laying a theoretical foundation for sustainable development in the sugarcane industry.PMID:37762388 | DOI:10.3390/ijms241814086

Int J Mol Sci. 2023 Sep 13;24(18):14054. doi: 10.3390/ijms241814054.ABSTRACTThe diagnosis of ewes' pregnancy status at an early stage is an efficient way to enhance the reproductive output of sheep and allow producers to optimize production and management. The techniques of proteomics and metabolomics have been widely used to detect regulatory factors in various physiological processes of animals. The aim of this study is to explore the differential metabolites and proteins in the serum of pregnant and non-pregnant ewes by proteomics and metabolomics. The serum of ewes at 21, 28 and 33 days after artificial insemination (AI) were collected. The pregnancy stratus of the ewes was finally determined through ultrasound examination and then the ewes were grouped as Pregnant (n = 21) or N on-pregnant (n = 9). First, the serum samples from pregnant or non-pregnant ewes at 21 days after AI were selected for metabolomic analysis. It was found that the level of nine metabolites were upregulated and 20 metabolites were downregulated in the pregnant animals (p < 0.05). None of these differential metabolomes are suitable as markers of pregnancy due to their small foldchange. Next, the proteomes of serum from pregnant or non-pregnant ewes were evaluated. At 21 days after AI, the presence of 321 proteins were detected, and we found that the level of three proteins were upregulated and 11 proteins were downregulated in the serum of pregnant ewes (p < 0.05). The levels of serum amyloid A (SAA), afamin (AFM), serpin family A member 6 (SERPINA6) and immunoglobulin-like domain-containing protein between pregnant and non-pregnant ewes at 21-, 28- and 33-days post-AI were also analyzed via enzyme-linked immunosorbent assay (ELISA). The levels of SAA and AFM were significantly higher in pregnant ewes than in non-pregnant ewes, and could be used as markers for early pregnancy detection. Overall, our results show that SAA and AFM are potential biomarkers to determine the early pregnancy status of ewes.PMID:37762358 | DOI:10.3390/ijms241814054

Int J Mol Sci. 2023 Sep 13;24(18):14043. doi: 10.3390/ijms241814043.ABSTRACTAging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. Although not usually considered a pathogenic event, photoaging affects cutaneous biology, increasing the risk of skin carcinogenesis. At the cellular level, aging is typified by the rise of senescence cells a condition characterized by reduced or absent capacity to proliferate and aberrant hyper-secretory activity. Senescence has a double-edged sword in cancer biology given that senescence prevents the uncontrolled proliferation of damaged cells and favors their clearance by paracrine secretion. Nevertheless, the cumulative insults and the poor clearance of injured cells in the elderly increase cancer incidence. However, there are not conclusive data proving that aged skin represents a permissive milieu for tumor onset. On the other hand, tumor cells are capable of activating resident fibroblasts onto a pro-tumorigenic phenotype resembling those of senescent fibroblasts suggesting that aged fibroblasts might facilitate cancer progression. This review discusses changes that occur during aging that can prime neoplasm or increase the aggressiveness of melanoma and non-melanoma skin cancer.PMID:37762344 | DOI:10.3390/ijms241814043

Int J Mol Sci. 2023 Sep 12;24(18):13997. doi: 10.3390/ijms241813997.ABSTRACTNon-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide; it is characterized by hepatic lipid accumulation, inflammation, and progressive fibrosis. Here, a Western diet combined with low-dose weekly carbon tetrachloride was fed to C57BL/6J mice for 12 weeks to build a NASH model to investigate the attenuating effects and possible mechanisms of Lactiplantibacillus plantarum LPJZ-658. Hepatic pathology, lipid profiles, and gene expression were assessed. The metabolomic profiling of the serum was performed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. The results show that LPJZ-658 treatment significantly attenuated liver injury, steatosis, fibrosis, and inflammation in NASH mice. Metabolic pathway analysis revealed that several pathways, such as purine metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and primary bile acid biosynthesis, were associated with NASH. Notably, we found that treatment with LPJZ-658 regulated the levels of bile acids (BAs) in the serum. Moreover, LPJZ-658 restored NASH-induced gut microbiota dysbiosis. The correlation analysis deduced obvious interactions between BAs and gut microbiota. The current study indicates that LPJZ-658 supplementation protects against NASH progression, which is accompanied by alternating BA metabolic and modulating gut microbiota.PMID:37762300 | DOI:10.3390/ijms241813997

Int J Mol Sci. 2023 Sep 12;24(18):13993. doi: 10.3390/ijms241813993.ABSTRACTAffected by global warming; heat stress is the main limiting factor for crop growth and development. Brassica rapa prefers cool weather, and heat stress has a significant negative impact on its growth, development, and metabolism. Understanding the regulatory patterns of heat-resistant and heat-sensitive varieties under heat stress can help deepen understanding of plant heat tolerance mechanisms. In this study, an integrative analysis of transcriptome and metabolome was performed on the heat-tolerant ('WYM') and heat-sensitive ('AJH') lines of Brassica rapa to reveal the regulatory networks correlated to heat tolerance and to identify key regulatory genes. Heat stress was applied to two Brassica rapa cultivars, and the leaves were analyzed at the transcriptional and metabolic levels. The results suggest that the heat shock protein (HSP) family, plant hormone transduction, chlorophyll degradation, photosynthetic pathway, and reactive oxygen species (ROS) metabolism play an outstanding role in the adaptation mechanism of plant heat tolerance. Our discovery lays the foundation for future breeding of horticultural crops for heat resistance.PMID:37762295 | DOI:10.3390/ijms241813993

Int J Mol Sci. 2023 Sep 12;24(18):13966. doi: 10.3390/ijms241813966.ABSTRACT(1) Carfilzomib (Cfz) is an antineoplastic agent indicated for the treatment of multiple myeloma. However, its beneficial action is attenuated by the occurrence of cardiotoxicity and nephrotoxicity as the most common adverse effects. Presently, there is well-established knowledge on the pathomechanisms related to these side effects; however, the research on the metabolic alterations provoked by the drug is limited. (2) An in vivo simulation of Cfz-induced toxicity was developed in (i) Cfz-treated and (ii) control mice. An RP-HRMS-based protocol and an advanced statistical treatment were used to investigate the impact of Cfz on the non-polar metabolome. (3) The differential analysis classified the Cfz-treated and control mice and resulted in a significant number of identified biomarkers with AUC > 0.9. The drug impaired the biosynthesis and degradation of aromatic amino acids (AAA) and led to alterations of uremic toxins in the renal and urine levels. Furthermore, the renal degradation of tryptophan was affected, inducing its degradation via the kynurenine pathway. (4) The renal levels of metabolites showed impaired excretion and degradation of AAAs. Cfz was, finally, correlated with the biosynthesis of renal dopamine, explaining the biochemical causes of water and ion retention and the increase in systolic pressure.PMID:37762269 | DOI:10.3390/ijms241813966

Int J Mol Sci. 2023 Sep 11;24(18):13961. doi: 10.3390/ijms241813961.ABSTRACTLipidomics is a comprehensive study of all lipid components in living cells, serum, plasma, or tissues, with the aim of discovering diagnostic, prognostic, and predictive biomarkers for diseases such as malignant tumors. This systematic review evaluates studies, applying lipidomics to the diagnosis, prognosis, prediction, and differentiation of malignant and benign ovarian tumors. A literature search was performed in PubMed, Science Direct, and SciFinder. Only publications written in English after 2012 were included. Relevant citations were identified from the reference lists of primary included studies and were also included in our list. All studies included referred to the application of lipidomics in serum/plasma samples from human cases of OC, some of which also included tumor tissue samples. In some of the included studies, metabolome analysis was also performed, in which other metabolites were identified in addition to lipids. Qualitative data were assessed, and the risk of bias was determined using the ROBINS-I tool. A total of twenty-nine studies were included, fifteen of which applied non-targeted lipidomics, seven applied targeted lipidomics, and seven were reviews relevant to our objectives. Most studies focused on the potential application of lipidomics in the diagnosis of OC and showed that phospholipids and sphingolipids change most significantly during disease development. In conclusion, this systematic review highlights the potential contribution of lipids as biomarkers in OC management.PMID:37762264 | DOI:10.3390/ijms241813961

Int J Mol Sci. 2023 Sep 11;24(18):13959. doi: 10.3390/ijms241813959.ABSTRACTSymptoms of oral discomfort such as dry mouth are common in older people wearing dentures. Such symptoms are mainly treated symptomatically. Many of these symptoms are related to saliva, and associations with salivary volume have been reported. Although denture treatment improves symptoms by increasing the amount of saliva, the effects on salivary components remain unclear. This study aimed to investigate the effects of denture treatment on salivary metabolite changes based on salivary metabolome analyses. We enrolled 21 patients requiring denture treatment. At the first visit, and after completion of denture treatment, saliva outflow was measured under resting and stimulated conditions, samples for salivary metabolite analysis were collected, and masticatory efficiency was tested. In all participants, masticatory efficiency increased after denture treatment. Moreover, the amounts of resting and stimulated saliva were increased. Using salivary metabolome analysis, 61 salivary metabolites were detected. Substantial concentration changes were observed for 4 and 21 metabolites in resting and stimulated saliva, respectively. The four metabolites common to both saliva tests had significantly lower concentrations after treatment. These results suggest that the improvement in masticatory function by dentures is related not only to salivary secretion volume, but also to salivary metabolite composition.PMID:37762262 | DOI:10.3390/ijms241813959

Int J Mol Sci. 2023 Sep 11;24(18):13952. doi: 10.3390/ijms241813952.ABSTRACTThis study investigated whether dietary supplementation with magnolol affects growth performance, anti-inflammatory abilities, serum and muscle amino acid profiles, and metabolisms in growing pigs. A total of 42 seventy-days-old growing barrows (Duroc × Landrace × Yorkshire) were randomly allocated into two dietary groups: Con, control group (basal diet); and Mag, magnolol group (basal diet supplemented with 400 mg/kg of magnolol). The results revealed that dietary supplementation with magnolol had no effect (p > 0.05) on growth performance. However, magnolol supplementation remarkably increased (p < 0.05) the serum content of albumin, total protein, immunoglobulin G, immunoglobulin M, and interleukin-22. In addition, dietary magnolol supplementation altered the amino acid (AA) profiles in serum and dorsal muscle and particularly increased (p < 0.05) the serum content of arginine and muscle glutamate. Simultaneously, the mRNA expression of genes associated with AA transport in jejunum (SLC38A2, SLC1A5, and SLC7A1) and ileum (SLC1A5 and SLC7A1) was higher (p < 0.05) in the Mag group than in the Con group. Additionally, the serum metabolomics analysis showed that the addition of magnolol significantly enhanced (p < 0.05) arginine biosynthesis, as well as D-glutamine and D-glutamate metabolism. Overall, these results suggested that dietary supplementation with magnolol has the potential to improve the accumulation of AAs, protein synthesis, immunity, and body health in growing pigs by increasing intestinal absorption and the transport of AAs.PMID:37762256 | DOI:10.3390/ijms241813952

Int J Mol Sci. 2023 Sep 8;24(18):13872. doi: 10.3390/ijms241813872.ABSTRACTBy means of liquid chromatography combined with high-resolution mass spectrometry, metabolite profiling was performed on an aqueous-ethanol extract from Spiraea hypericifolia (Rosaceae) collected in Siberia (Russia). Up to 140 compounds were found in the extract, of which 47 were tentatively identified. The identified compounds were amino acids, sugars, phenylpropanoids, fatty acids and their derivatives, triterpenoids, flavonoids, and others. A quantitative analysis showed the predominance of phenolcarboxylic acids and flavonoids in the studied extract, but a qualitative analysis revealed the higher structural diversity of flavonoids. Of the 23 identified flavonoids, 13 were flavonols: quercetin, hyperoside, isoquercitrin, reynoutrin, avicularin, rutin, quercetin-3-O-(6″-O-malonyl)-β-D-glucoside, 3-O-methylquercetin-3'-O-β-D-glucopyranoside, isorhamnetin, rhamnetin-3-O-β-D-xylopyranosyl-β-D-glucopyranoside, kaempferol, tiliroside, and trifolin; six were catechins: catechin, (-)-epicatechin, (+)-epicatechin, (+)-catechin-7-O-β-D-xyloside, (2S,3R)-3,5-dihydroxy-2-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-7-yl-β-D-glucopyranoside, and catechin 7-O-apiofuranoside; two are isoflavones: genistin and genistein; and one was a flavone (luteolin-4'-O-β-D-glucopyranoside) and another was an anthocyanidin (pelargonidin). The aqueous-ethanol extract from S. hypericifolia showed antioxidant activity (half-maximal inhibitory concentration 102.95 μg/mL), which was likely related to the high concentrations of phenolcarboxylic acids (229.6 mg/g), flavonoids (118.3 mg/g), and tannins (62.9 mg/g).PMID:37762175 | DOI:10.3390/ijms241813872

Int J Mol Sci. 2023 Sep 7;24(18):13787. doi: 10.3390/ijms241813787.ABSTRACTThe COVID-19 pandemic has raised questions about indirect impact in pregnant women on the development of their future children. Investigating the characteristics of lipid metabolism in the "mother-placenta-fetus" system can give information about the pathophysiology of COVID-19 infection during pregnancy. A total of 234 women were included in study. Maternal plasma, cord blood, and amniotic fluid lipidome were analyzed using HPLC-MS/MS. Differences in lipid profile were searched by Mann-Whitney and Kruskall-Wallis test, and diagnostic model based on logistic regression were built by AIC. Elevated levels of lysophospholipids, triglycerides, sphingomyelins, and oxidized lipids were registered in patients' maternal and cord plasma after COVID-19 infection. An increase in maternal plasma sphingomyelins and oxidized lipids was observed in cases of infection during the second trimester. In amniotic fluid, compared to the control group, nine lipids were reduced and six were elevated. Levels of phosphoglycerides, lysophosphoglycerides, and phosphatidylinositols decreased during infection in the second and third trimesters of pregnancy. A health diagnostic model for newborns based on maternal plasma was developed for each group and exhibited good diagnostic value (AUC > 0.85). Maternal and cord plasma's lipidome changes during delivery, which are associated with COVID-19 infection during pregnancy, are synergistic. The most significant disturbances occur with infections in the second trimester of pregnancy.PMID:37762087 | DOI:10.3390/ijms241813787

Int J Mol Sci. 2023 Sep 7;24(18):13784. doi: 10.3390/ijms241813784.ABSTRACTClostridium butyricum, a new probiotic in recent years, can produce butyric acid and short-chain fatty acids. It has the characteristics of strong acid and alkali resistance, high temperature resistance, and strong resistance to most antibiotics, and has more advantages than other probiotics. However, the action mechanism of C. butyricum on Eriocheir sinensis is still unclear and needs further study. In this study, when C. butyricum was added to the basic diet, the number of living bacteria was 0, 1 × 106 and 1 × 108 CFU/g, respectively. The E. sinensis were randomly divided into three groups: (blank control group, experimental group 1 (1 × 106 CFU/g) and experimental group 2 (1 × 108 CFU/g)). They were fed an experimental diet for 28 days. The effects of C. butyricum on E. sinensis were studied by detecting the differences in non-specific immune indexes, intestinal microflora, and metabolites between serum and hepatopancreas. The results showed that C. butyricum could improve the antioxidant ability of E. sinensis serum and hepatopancreas, protect intestinal tissues, and promote the absorption of nutrients. At the same time, it can enhance the microbial diversity and richness of the E. sinensis gut flora. LC-MS metabolomics was used to detect the metabolism of intestinal flora. It was found that C. butyricum could up-regulate lysophosphatidylcholine in the intestine. Through the KEGG enrichment pathway, it was found that significantly different metabolites were mainly concentrated in six metabolic pathways. The purine metabolism and alanine, aspartate, and glutamate metabolism pathways showed a downward trend, indicating that the addition of C. butyricum to feed could reduce purine metabolism, promote the water-salt balance of the organism's cells, and reduce inflammation. In this study, it was found that the addition of certain concentrations of C. butyricum to feed could improve the antioxidant ability of E. sinensis, improve the intestinal flora environment, and promote the growth of beneficial bacteria in the gut. This can promote the body's metabolism, which is more conducive to its growth.PMID:37762084 | DOI:10.3390/ijms241813784

Int J Mol Sci. 2023 Sep 6;24(18):13732. doi: 10.3390/ijms241813732.ABSTRACTCurrently, the leaves of the hop plant (Humulus lupulus L.) are an unexploited and still little-investigated agricultural by-product. In our study, with the aim of exploring the metabolome of dried hop leaves (Chinook cultivar), a metabolomic approach was applied using multiple analytical tools such as SPME/GC-MS, GC-MS, PTR-ToF-MS, and NMR to identify the secondary metabolites. The obtained results showed the presence of a high number of components belonging to different chemical classes. In fact, thanks to the multi-methodological approach, volatile organic compounds (VOCs) with low molecular weight, terpenic compounds, fatty acids, sugars, amino acids, organic acids, and alcohols have been detected and identified. Among the revealed terpenes in the untreated matrix, the sesquiterpenes α-humulene, β-caryophyllene, and α-copaene were the most abundant. Among the saturated and unsaturated fatty acids, palmitic and linolenic acids, respectively, were those with the highest relative percentages. Particularly relevant was the sugar content, where sucrose was the main exponent while glutamate and asparagine were the principal detected amino acids. Conversely, alcohols and organic acids were the least abundant compound classes, and xanthohumol was also identified in the methanolic extract.PMID:37762036 | DOI:10.3390/ijms241813732

Int J Mol Sci. 2023 Sep 6;24(18):13724. doi: 10.3390/ijms241813724.ABSTRACTGestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance, with hyperglycemia of varying severity with onset during pregnancy. An uncontrolled GDM can lead to an increased risk of morbidity in the fetus and newborn, and an increased risk of obesity or developing type 2 diabetes, hypertension or neurocognitive developmental impairment in adulthood. In this study, we used nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GS-MS) to analyze the urinary metabolomic profile of newborns of diabetic mothers (NDMs) with the aim of identifying biomarkers useful for the monitoring of NDMs and for early diagnosis of predisposition to develop related chronic diseases. A total of 26 newborns were recruited: 21 children of diabetic mothers, comprising 13 in diet therapy (NDM-diet) and 8 in insulin therapy (NDM-insulin), and 5 control children of non-diabetic mothers (CTR). Urine samples were collected at five time points: at birth (T1), on the third day of life (T2), one week (T3), one month (T4) and six months postpartum (T5). At T1, variations were observed in the levels of seven potential biomarkers (acetate, lactate, glycylproline/proline, isocitrate, N,N-dimethylglycine, N-acetylglucosamine and N-carbamoyl-aspartate) in NMD-insulin infants compared to NDM-diet and CTR infants. In particular, the altered metabolites were found to be involved in several metabolic pathways such as citrate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, amino sugar and nucleotide sugar metabolism, and pyruvate metabolism. In contrast, these changes were not visible at subsequent sampling times. The impact of early nutrition (maternal and formula milk) on the metabolomic profile was considered as a potential contributing factor to this finding.PMID:37762025 | DOI:10.3390/ijms241813724

Int J Mol Sci. 2023 Sep 5;24(18):13695. doi: 10.3390/ijms241813695.ABSTRACTThe purpose of this study was to elucidate the metabolic action patterns of P. forrestii against rheumatoid arthritis (RA) using metabolomics, and to obtain its potential effective substances for treating RA. First, the therapeutic effects of P. forrestii against RA were confirmed; second, the chemical composition of P. forrestii was analyzed, and 17 prototypes were absorbed into blood; subsequently, plasma metabolomics studies using UPLC-Triple-TOF-MS/MS and GC-MS were performed to disclose the metabolomics alterations in groups, which revealed 38 altered metabolites after drug intervention. These metabolites were all associated with the arthritis pathophysiology process (-log(p) > 1.6). Among them, sorted by variable important in projection (VIP), the metabolites affected (VIP ≥ 1.72) belonged to lipid metabolites. Finally, Pearson's analysis between endogenous metabolites and exogenous compounds was conducted to obtain potential pharmacological substances for the P. forrestii treatment of RA, which showed a high correlation between five blood-absorbed components and P. forrestii-regulated metabolites. This information provides a basis for the selection of metabolic action modes for P. forrestii clinical application dosage, and potential pharmacological substances that exerted anti-RA effects of P. forrestii were discovered. The study provided an experimental basis for further research on pharmacoequivalence, molecular mechanism validation, and even the development of new dosage forms in the future.PMID:37761998 | DOI:10.3390/ijms241813695

Biochemistry (Mosc). 2023 Aug;88(8):1061-1069. doi: 10.1134/S0006297923080023.ABSTRACTActivation of the constitutive androstane receptor (CAR, NR1I3) by chemical compounds induces liver hyperplasia in rodents. 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a mouse CAR agonist, is most often used to study chemically induced liver hyperplasia and hepatocyte proliferation in vivo. TCPOBOP is a potent murine liver chemical mitogen, which induces rapid liver hyperplasia in mice independently of liver injury. In recent years, great amount of data has been accumulated on the transcription program that characterizes the TCPOBOP-induced hepatocyte proliferation. However, there are only few data about the metabolic requirements of hepatocytes that divide upon exposure to xenobiotics. In the present study, we have employed liquid chromatography - mass spectrometry technology combined with statistical analysis to investigate metabolite profile of small biomolecules, in order to identify key metabolic changes in the male mouse liver tissue after TCPOBOP administration. Analysis of biochemical pathways of the differentially affected metabolites in the mouse liver demonstrated significant TCPOBOP-mediated enrichment of several processes including those associated with nucleotide metabolism, amino acid metabolism, and energy substrate metabolism. Our findings provide evidence to support the conclusion that the CAR agonist, TCPOBOP, initiates an intracellular program that promotes global coordinated metabolic activities required for hepatocyte proliferation. Our metabolic data might provide novel insight into the biological mechanisms that occur during the TCPOBOP-induced hepatocyte proliferation in mice.PMID:37758307 | DOI:10.1134/S0006297923080023