PubMed

Metabolites. 2024 Mar 30;14(4):196. doi: 10.3390/metabo14040196.ABSTRACTRespiratory distress syndrome (RDS) is a major morbidity of prematurity. In this case-control study, we prospectively evaluated whether untargeted metabolomic analysis (gas chromatography-mass spectrometry) of the gastric fluid could predict the need for surfactant in very preterm neonates. 43 infants with RDS necessitating surfactant (cases) were compared with 30 infants who were not treated with surfactant (controls). Perinatal-neonatal characteristics were recorded. Significant differences in gastric fluid metabolites (L-proline, L-glycine, L-threonine, acetyl-L-serine) were observed between groups, but none could solely predict surfactant administration with high accuracy. Univariate analysis revealed significant predictors of surfactant administration involving gastric fluid metabolites (L-glycine, acetyl-L-serine) and clinical parameters (gestational age, Apgar scores, intubation in the delivery room). Multivariable models were constructed for significant clinical variables as well as for the combination of clinical variables and gastric fluid metabolites. The AUC value of the first model was 0.69 (95% CI 0.57-0.81) and of the second, 0.76 (95% CI 0.64-0.86), in which acetyl-L-serine and intubation in the delivery room were found to be significant predictors of surfactant therapy. This investigation adds to the current knowledge of biomarkers in preterm neonates with RDS, but further research is required to assess the predictive value of gastric fluid metabolomics in this field.PMID:38668324 | DOI:10.3390/metabo14040196

Metabolites. 2024 Mar 30;14(4):195. doi: 10.3390/metabo14040195.ABSTRACTThe COVID-19 pandemic has brought about diverse impacts on the global population. Individuals with comorbidities were more susceptible to the severe symptoms caused by the virus. Within the crisis scenario, metabolomics represents a potential area of science capable of providing relevant information for understanding the metabolic pathways associated with the intricate interaction between the viral disease and previous comorbidities. This work aims to provide a comprehensive description of the scientific production pertaining to metabolomics within the specific context of COVID-19 and comorbidities, while highlighting promising areas for exploration by those interested in the subject. In this review, we highlighted the studies of metabolomics that indicated a variety of metabolites associated with comorbidities and COVID-19. Furthermore, we observed that the understanding of the metabolic processes involved between comorbidities and COVID-19 is limited due to the urgent need to report disease outcomes in individuals with comorbidities. The overlap of two or more comorbidities associated with the severity of COVID-19 hinders the comprehension of the significance of each condition. Most identified studies are observational, with a restricted number of patients, due to challenges in sample collection amidst the emergent situation.PMID:38668323 | DOI:10.3390/metabo14040195

Metabolites. 2024 Mar 28;14(4):191. doi: 10.3390/metabo14040191.ABSTRACTLittle is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.PMID:38668319 | DOI:10.3390/metabo14040191

Metabolites. 2024 Mar 27;14(4):189. doi: 10.3390/metabo14040189.ABSTRACTThe wide spread of microplastics has fueled growing public health concern globally. Due to their porous structure and large surface area, microplastics can serve as carriers for other environmental pollutants, including heavy metals. Although the toxic effects of microplastics or heavy metals have been reported previously, investigations into the sex-differential health effects of combined exposure to microplastics and heavy metals are lacking. In the present study, the effects of polystyrene microplastics and lead(II) co-exposure on the gut microbiome, intestinal permeability, and fecal metabolome were examined in both male and female mice. Combined exposure of polystyrene microplastics and lead(II) increased intestinal permeability in both male and female mice. Sex-specific responses to the co-exposure were found in gut bacteria, fungi, microbial metabolic pathways, microbial genes encoding antibiotic resistance and virulence factors, as well as fecal metabolic profiles. In particular, Shannon and Simpson indices of gut bacteria were reduced by the co-exposure only in female mice. A total of 34 and 13 fecal metabolites were altered in the co-exposure group in female and male mice, respectively, among which only three metabolites were shared by both sexes. These sex-specific responses to the co-exposure need to be taken into consideration when investigating the combined toxic effects of microplastics and heavy metals on the gut microbiota.PMID:38668317 | DOI:10.3390/metabo14040189

Metabolites. 2024 Mar 25;14(4):184. doi: 10.3390/metabo14040184.ABSTRACTOrbitrap mass spectrometry in full scan mode enables the simultaneous detection of hundreds of metabolites and their isotope-labeled forms. Yet, sensitivity remains limiting for many metabolites, including low-concentration species, poor ionizers, and low-fractional-abundance isotope-labeled forms in isotope-tracing studies. Here, we explore selected ion monitoring (SIM) as a means of sensitivity enhancement. The analytes of interest are enriched in the orbitrap analyzer by using the quadrupole as a mass filter to select particular ions. In tissue extracts, SIM significantly enhances the detection of ions of low intensity, as indicated by improved signal-to-noise (S/N) ratios and measurement precision. In addition, SIM improves the accuracy of isotope-ratio measurements. SIM, however, must be deployed with care, as excessive accumulation in the orbitrap of similar m/z ions can lead, via space-charge effects, to decreased performance (signal loss, mass shift, and ion coalescence). Ion accumulation can be controlled by adjusting settings including injection time and target ion quantity. Overall, we suggest using a full scan to ensure broad metabolic coverage, in tandem with SIM, for the accurate quantitation of targeted low-intensity ions, and provide methods deploying this approach to enhance metabolome coverage.PMID:38668312 | DOI:10.3390/metabo14040184

Metabolites. 2024 Mar 25;14(4):183. doi: 10.3390/metabo14040183.ABSTRACTOsteoarthritis (OA) is a chronic joint disease with heterogenous metabolic pathology. To gain insight into OA-related metabolism, metabolite extracts from healthy (n = 11) and end-stage osteoarthritic cartilage (n = 35) were analyzed using liquid chromatography-mass spectrometry metabolomic profiling. Specific metabolites and metabolic pathways, including lipid and amino acid pathways, were differentially regulated in osteoarthritis-derived and healthy cartilage. The detected alterations in amino acids and lipids highlighted key differences in bioenergetic resources, matrix homeostasis, and mitochondrial alterations in OA-derived cartilage compared to healthy cartilage. Moreover, the metabolomic profiles of osteoarthritic cartilage separated into four distinct endotypes, highlighting the heterogenous nature of OA metabolism and the diverse landscape within the joint in patients. The results of this study demonstrate that human cartilage has distinct metabolomic profiles in healthy and end-stage OA patients. By taking a comprehensive approach to assess metabolic differences between healthy and osteoarthritic cartilage and within osteoarthritic cartilage alone, several metabolic pathways with distinct regulation patterns were detected. Additional investigation may lead to the identification of metabolites that may serve as valuable indicators of disease status or potential therapeutic targets.PMID:38668311 | DOI:10.3390/metabo14040183

Metabolites. 2024 Mar 23;14(4):180. doi: 10.3390/metabo14040180.ABSTRACTFlavonoids and alkaloids are the major active ingredients in mulberry leaves that have outstanding medicinal value. Bacillus subtilis can effectively activate the plants defense response and regulate the plant secondary metabolism. In this study, we explored the effects of soil application of B. subtilis on the content of flavonoids and the most important alkaloids (1-deoxynojirimycin, DNJ) in mulberry leaves. Significant decreases in flavonoid content were observed in tender leaves and mature leaves after treatment with B. subtilis; at the same time, significant increases in DNJ content were observed in tender leaves. Based on widely targeted LC-MS/MS and high-throughput approaches, we screened out 904 differentially synthesized metabolites (DSMs) and 9715 differentially expressed genes (DEGs). KEGG analyses showed that these DSMs and DEGs were both significantly enriched in the biosynthesis of secondary metabolites, flavonoid synthesis and plant hormone signal transduction. Further correlation analysis of DEMs and DEGs showed that 40 key genes were involved in flavonoid biosynthesis, with 6 key genes involved in DNJ biosynthesis. The expression of CHS, CHI, F3H, F3'H, FLS, UGT and AOC significantly responded to B. subtilis soil application. This study broadens our understanding of the molecular mechanisms underlying the accumulation of flavonoids and alkaloids in mulberry leaves.PMID:38668308 | DOI:10.3390/metabo14040180

Metabolites. 2024 Mar 22;14(4):177. doi: 10.3390/metabo14040177.ABSTRACTIn the context of dietary transition toward plant proteins, it is necessary to ensure protein security in populations. It would thus be of interest to identify biomarkers of altered protein digestibility in populations. We examined the association between urinary metabolites and the acute intake of low- or highly digestible protein in healthy volunteers. The urine samples were collected before and 9 h after the ingestion of a meal containing either no protein, zein (low-digestible) or whey protein isolate (highly digestible). The liquid chromatography-high resolution mass spectrometry metabolomics approach was used for the profiling of the urinary metabolites. For the standardization of metabolomics data sets, osmolality-based, standard normal variates (SNV) and probabilistic quotient normalization (PQN) techniques were used. The ANOVA-based factorial method, AComDim_ICA, was used for chemometrics analysis. The osmolality adjustment has a beneficial effect and the subsequent mathematical normalization improves the chemometric analysis further. Some changes in the urinary metabolomes were observed 9 h after the meal in the three groups. However, there was no difference in the urine metabolome between groups. No biomarker of protein digestibility can be identified after the ingestion of a single meal, even when marked differences in the digestion efficiency of protein have been observed.PMID:38668305 | DOI:10.3390/metabo14040177

Metabolites. 2024 Mar 22;14(4):176. doi: 10.3390/metabo14040176.ABSTRACTThe quality of crops is closely associated with their geographical location and yield, which is reflected in the composition of their metabolites. Hence, we employed GC-MS pseudotargeted metabolomics to investigate the metabolic characteristics of high-, medium-, and low-yield Nicotiana tabacum (tobacco) leaves from the Bozhou (sweet honey flavour) and Shuicheng (light flavour) regions of Guizhou Province. A total of 124 metabolites were identified and classified into 22 chemical categories. Principal component analysis revealed that the geographical location exerted a greater influence on the metabolic profiling than the yield. Light-flavoured tobacco exhibited increased levels of sugar metabolism- and glycolysis-related intermediate products (trehalose, glucose-6-phosphate, and fructose-6-phosphate) and a few amino acids (proline and leucine), while sweet honey-flavoured tobacco exhibited increases in the tricarboxylic acid cycle (TCA cycle) and the phenylpropane metabolic pathway (p-hydroxybenzoic acid, caffeic acid, and maleic acid). Additionally, metabolite pathway enrichment analysis conducted at different yields and showed that both Shuicheng and Bozhou exhibited changes in six pathways and four of them were the same, mainly C/N metabolism. Metabolic pathway analysis revealed higher levels of intermediates related to glycolysis and sugar, amino acid, and alkaloid metabolism in the high-yield samples, while higher levels of phenylpropane in the low-yield samples. This study demonstrated that GC-MS pseudotargeted metabolomics-based metabolic profiling can be used to effectively discriminate tobacco leaves from different geographical locations and yields, thus facilitating a better understanding of the relationship between metabolites, yield, and geographical location. Consequently, metabolic profiles can serve as valuable indicators for characterizing tobacco yield and geographical location.PMID:38668304 | DOI:10.3390/metabo14040176

J Fungi (Basel). 2024 Mar 27;10(4):254. doi: 10.3390/jof10040254.ABSTRACTFlavonoids are a diverse family of natural compounds that are widely distributed in plants and play a critical role in plant growth, development, and stress adaptation. In recent years, the biosynthesis of flavonoids in plants has been well-researched, with the successive discovery of key genes driving this process. However, the regulation of flavonoid biosynthesis in fungi remains unclear. Stropharia rugosoannulata is an edible mushroom known for its high nutritional and pharmacological value, with flavonoids being one of its main active components. To investigate the flavonoid content of S. rugosoannulata, a study was conducted to extract and determine the total flavonoids at four stages: young mushroom (Ym), gill (Gi), maturation (Ma), and parachute-opening (Po). The findings revealed a gradual increase in total flavonoid concentration as the fruiting body developed, with significant variations observed between the Ym, Gi, and Ma stages. Subsequently, we used UPLC-MS/MS and transcriptome sequencing (RNA-seq) to quantify the flavonoids and identify regulatory genes of Ym, Gi, and Ma. In total, 53 flavonoid-related metabolites and 6726 differentially expressed genes (DEGs) were identified. Through KEGG pathway enrichment analysis, we identified 59 structural genes encoding flavonoid biosynthesis-related enzymes, most of which were up-regulated during the development of the fruiting body, consistent with the accumulation of flavonoids. This research led to the establishment of a comprehensive transcriptional metabolic regulatory network encompassing flavonoids, flavonoid synthases, and transcription factors (TFs). This represents the first systematic exploration of the molecular mechanism of flavonoids in the fruiting of fungi, offering a foundation for further research on flavonoid mechanisms and the breeding of high-quality S. rugosoannulata.PMID:38667925 | DOI:10.3390/jof10040254

Mar Drugs. 2024 Apr 20;22(4):187. doi: 10.3390/md22040187.ABSTRACTHigh blood cholesterol levels are a major risk factor for cardiovascular diseases. A purified aqueous extract of Fucus vesiculosus, rich in phlorotannins and peptides, has been described for its potential to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect of this extract on intestinal cells' metabolites and proteins was analysed to gain a deeper understanding of its mode of action on lipids' metabolism, particularly concerning the absorption and transport of exogenous cholesterol. Caco-2 cells, differentiated into enterocytes, were exposed to the extract, and analysed by untargeted metabolomics and proteomics. The results of the metabolomic analysis showed statistically significant differences in glutathione content of cells exposed to the extract compared to control cells, along with an increased expression of fatty acid amides in exposed cells. A proteomic analysis showed an increased expression in cells exposed to the extract compared to control cells of FAB1 and NPC1, proteins known to be involved in lipid metabolism and transport. To the extent of our knowledge, this study is the first use of untargeted metabolomics and a proteomic analysis to investigate the effects of F. vesiculosus on differentiated Caco-2 cells, offering insights into the molecular mechanism of the extract's compounds on intestinal cells.PMID:38667804 | DOI:10.3390/md22040187

Insects. 2024 Apr 21;15(4):294. doi: 10.3390/insects15040294.ABSTRACTIn this study, the changes in the conventional nutrient and mineral compositions as well as the metabolomics characteristics of the red palm weevil (RPW) Rhynchophus ferrugineus Olivier (Curculionidae: Coleoptera) larvae at early (EL), middle (ML) and old (OL) developmental stages were investigated. Results showed that the EL and ML had the highest content of protein (53.87 g/100 g dw) and fat (67.95 g/100 g), respectively, and three kinds of RPW larvae were all found to be rich in unsaturated fatty acids (52.17-53.12%), potassium (5707.12-15,865.04 mg/kg) and phosphorus (2123.87-7728.31 mg/kg). In addition, their protein contained 17 amino acids with the largest proportion of glutamate. A total of 424 metabolites mainly including lipids and lipid-like molecules, organic acids and their derivatives, organic heterocycle compounds, alkaloids and their derivatives, etc. were identified in the RPW larvae. There was a significant enrichment in the ABC transport, citrate cycle (TCA cycle), aminoacyl-tRNA biosynthesis, and mTOR signaling pathways as the larvae grow according to the analysis results of the metabolic pathways of differential metabolites. The water extract of EL exhibited relatively higher hydroxyl, 2,2-diphenyl-1-pyrroline hydrochloride (DPPH) and 2,2'-azobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging ability with the EC50 values of 1.12 mg/mL, 11.23 mg/mL, and 2.52 mg/mL, respectively. These results contribute to a better understanding of the compositional changes of the RPW larvae during its life cycle and provide a theoretical grounding for its deep processing and high-value utilization.PMID:38667424 | DOI:10.3390/insects15040294

Insects. 2024 Apr 19;15(4):291. doi: 10.3390/insects15040291.ABSTRACTArtificial silkworm diets significantly impact farm profitability. Sustainable cocoon production depends on the continuous improvement of feed efficiency to reduce costs and nutrient losses in the feed. This study used metabolomics to explore the differences in silkworm cocoons and hemolymph under two modes of rearing: an artificial diet and a mulberry-leaf diet. Nine metabolites of silkworm cocoons and hemolymph in the mulberry-leaf group were higher than those in the artificial-diet group. Enrichment analysis of the KEGG pathways for these metabolites revealed that they were mainly enriched in the valine, leucine, and isoleucine biosynthesis and degradation pathways. Hence, the artificial silkworm diet was supplemented various concentrations of valine were supplemented to with the aim of examining the impact of valine on their feeding and digestion of the artificial diet. The results indicated that valine addition had no significant effect on feed digestibility in the fifth-instar silkworm. Food intake in the 2% and 4% valine groups was significantly lower than that in the 0% valine group. However, the 2% and 4% valine groups showed significantly improved cocoon-production efficiency, at 11.3% and 25.1% higher, respectively. However, the cocoon-layer-production efficiencies of the 2% and 4% valine groups decreased by 7.7% and 13.9%, respectively. The research confirmed that valine is an effective substance for enhancing the feed efficiency of silkworms.PMID:38667421 | DOI:10.3390/insects15040291

Insects. 2024 Apr 11;15(4):263. doi: 10.3390/insects15040263.ABSTRACTThe queen bee is a central and pivotal figure within the colony, serving as the sole fertile female responsible for its reproduction. The queen possesses an open circulatory system, with her ovaries immersed in hemolymph. A continuous and intricate transportation and interchange of substances exist between the ovaries and hemolymph of queen bees. To determine the characteristic metabolites in the hemolymph and ovary, as well as understand how their rapid metabolism contributes to the process of egg-laying by queens, we reared Apis mellifera queens from three different age groups: newly emerged queen (NEQ), newly laying queen (NLQ), and old laying queen (OLQ). Using widely targeted metabolomics, our study revealed that the laying queen (NLQ and OLQ) exhibited faster fatty acid metabolism, up-regulated expression of antioxidants, and significant depletion of amino acids compared to the NEQ. This study revealed that the levels of carnitine and antioxidants (GSH, 2-O-α-D-glucopyranosyl-L-ascorbic acid, L-ascorbic acid 2-phosphate, etc.) in the NLQ and OLQ were significantly higher compared to NEQ. However, most of the differentially expressed amino acids, such as L-tryptophan, L-tyrosine, L-aspartic acid, etc., detected in NLQ and OLQ were down-regulated compared to the NEQ. Following egg-laying, pathways in the queens change significantly, e.g., Tryptophan metabolism, Tyrosine metabolism, cAMP signaling pathway, etc. Our results suggest that carnitine and antioxidants work together to maintain the redox balance of the queen. Additionally, various amino acids are responsible for maintaining the queen's egg production.PMID:38667393 | DOI:10.3390/insects15040263

Insects. 2024 Apr 8;15(4):254. doi: 10.3390/insects15040254.ABSTRACTThe recent dominance of Adelphocoris suturalis Jakovlev as the primary cotton field pest in Bt-cotton-cultivated areas has generated significant interest in cotton pest control research. This study addresses the limited understanding of cotton defense mechanisms triggered by A. suturalis feeding. Utilizing LC-QTOF-MS, we analyzed cotton metabolomic changes induced by A. suturalis, and identified 496 differential positive ions (374 upregulated, 122 downregulated) across 11 categories, such as terpenoids, alkaloids, phenylpropanoids, flavonoids, isoflavones, etc. Subsequent iTRAQ-LC-MS/MS analysis of the cotton proteome revealed 1569 differential proteins enriched in 35 metabolic pathways. Integrated metabolome and proteome analysis highlighted significant upregulation of 17 (89%) proteases in the α-linolenic acid (ALA) metabolism pathway, concomitant with a significant increase in 14 (88%) associated metabolites. Conversely, 19 (73%) proteases in the fructose and mannose biosynthesis pathway were downregulated, with 7 (27%) upregulated proteases corresponding to the downregulation of 8 pathway-associated metabolites. Expression analysis of key regulators in the ALA pathway, including allene oxidase synthase (AOS), phospholipase A (PLA), allene oxidative cyclase (AOC), and 12-oxophytodienoate reductase3 (OPR3), demonstrated significant responses to A. suturalis feeding. Finally, this study pioneers the exploration of molecular mechanisms in the plant-insect relationship, thereby offering insights into potential novel control strategies against this cotton pest.PMID:38667384 | DOI:10.3390/insects15040254

Cells. 2024 Apr 18;13(8):702. doi: 10.3390/cells13080702.ABSTRACTAnalysis of blood-based indicators of brain health could provide an understanding of early disease mechanisms and pinpoint possible intervention strategies. By examining lipid profiles in extracellular vesicles (EVs), secreted particles from all cells, including astrocytes and neurons, and circulating in clinical samples, important insights regarding the brain's composition can be gained. Herein, a targeted lipidomic analysis was carried out in EVs derived from plasma samples after removal of lipoproteins from individuals with Alzheimer's disease (AD) and healthy controls. Differences were observed for selected lipid species of glycerolipids (GLs), glycerophospholipids (GPLs), lysophospholipids (LPLs) and sphingolipids (SLs) across three distinct EV subpopulations (all-cell origin, derived by immunocapture of CD9, CD81 and CD63; neuronal origin, derived by immunocapture of L1CAM; and astrocytic origin, derived by immunocapture of GLAST). The findings provide new insights into the lipid composition of EVs isolated from plasma samples regarding specific lipid families (MG, DG, Cer, PA, PC, PE, PI, LPI, LPE, LPC), as well as differences between AD and control individuals. This study emphasizes the crucial role of plasma EV lipidomics analysis as a comprehensive approach for identifying biomarkers and biological targets in AD and related disorders, facilitating early diagnosis and potentially informing novel interventions.PMID:38667317 | DOI:10.3390/cells13080702

Cells. 2024 Apr 9;13(8):661. doi: 10.3390/cells13080661.ABSTRACTCancer cell lines are frequently used in metabolomics, such as in vitro tumor models. In particular, A2780 cells are commonly used as a model for ovarian cancer to evaluate the effects of drug treatment. Here, we compare the NMR metabolomics profiles of A2780 and cisplatin-resistant A2780 cells with those of cells derived from 10 patients with high-grade serous ovarian carcinoma (collected during primary cytoreduction before any chemotherapeutic treatment). Our analysis reveals a substantial similarity among all primary cells but significant differences between them and both A2780 and cisplatin-resistant A2780 cells. Notably, the patient-derived cells are closer to the resistant A2780 cells when considering the exo-metabolome, whereas they are essentially equidistant from A2780 and A2780-resistant cells in terms of the endo-metabolome. This behavior results from dissimilarities in the levels of several metabolites attributable to the differential modulation of underlying biochemical pathways. The patient-derived cells are those with the most pronounced glycolytic phenotype, whereas A2780-resistant cells mainly diverge from the others due to alterations in a few specific metabolites already known as markers of resistance.PMID:38667276 | DOI:10.3390/cells13080661

Biosensors (Basel). 2024 Mar 31;14(4):171. doi: 10.3390/bios14040171.ABSTRACTRaman flow cytometry (RFC) uniquely integrates the "label-free" capability of Raman spectroscopy with the "high-throughput" attribute of traditional flow cytometry (FCM), offering exceptional performance in cell characterization and sorting. Unlike conventional FCM, RFC stands out for its elimination of the dependency on fluorescent labels, thereby reducing interference with the natural state of cells. Furthermore, it significantly enhances the detection information, providing a more comprehensive chemical fingerprint of cells. This review thoroughly discusses the fundamental principles and technological advantages of RFC and elaborates on its various applications in the biomedical field, from identifying and characterizing cancer cells for in vivo cancer detection and surveillance to sorting stem cells, paving the way for cell therapy, and identifying metabolic products of microbial cells, enabling the differentiation of microbial subgroups. Moreover, we delve into the current challenges and future directions regarding the improvement in sensitivity and throughput. This holds significant implications for the field of cell analysis, especially for the advancement of metabolomics.PMID:38667164 | DOI:10.3390/bios14040171

Antibiotics (Basel). 2024 Apr 11;13(4):352. doi: 10.3390/antibiotics13040352.ABSTRACTSalmonella enterica serovar Typhimurium (S. Typhimurium), a foodborne pathogen that poses significant public health risks to humans and animals, presents a formidable challenge due to its antibiotic resistance. This study explores the potential of Lactobacillus acidophilus (L. acidophilus 1.3251) probiotics as an alternative strategy to combat antibiotic resistance associated with S. Typhimurium infection. In this investigation, twenty-four BALB/c mice were assigned to four groups: a non-infected, non-treated group (CNG); an infected, non-treated group (CPG); a group fed with L. acidophilus but not infected (LAG); and a group fed with L. acidophilus and challenged with Salmonella (LAST). The results revealed a reduction in Salmonella levels in the feces of mice, along with restored weight and improved overall health in the LAST compared to the CPG. The feeding of L. acidophilus was found to downregulate pro-inflammatory cytokine mRNA induced by Salmonella while upregulating anti-inflammatory cytokines. Additionally, it influenced the expression of mRNA transcript, encoding tight junction protein, oxidative stress-induced enzymes, and apoptosis-related mRNA expression. Furthermore, the LEfSe analysis demonstrated a significant shift in the abundance of critical commensal genera in the LAST, essential for maintaining gut homeostasis, metabolic reactions, anti-inflammatory responses, and butyrate production. Transcriptomic analysis revealed 2173 upregulated and 506 downregulated differentially expressed genes (DEGs) in the LAST vs. the CPG. Functional analysis of these DEGs highlighted their involvement in immunity, metabolism, and cellular development. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis indicated their role in tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), chemokine, Forkhead box O (FOXO), and transforming growth factor (TGF-β) signaling pathway. Moreover, the fecal metabolomic analysis identified 929 differential metabolites, with enrichment observed in valine, leucine, isoleucine, taurine, glycine, and other metabolites. These findings suggest that supplementation with L. acidophilus promotes the growth of beneficial commensal genera while mitigating Salmonella-induced intestinal disruption by modulating immunity, gut homeostasis, gut barrier integrity, and metabolism.PMID:38667028 | DOI:10.3390/antibiotics13040352

Biology (Basel). 2024 Apr 18;13(4):272. doi: 10.3390/biology13040272.ABSTRACTObesity is a socially significant disease that is characterized by a disproportionate accumulation of fat. It is also associated with chronic inflammation, cancer, diabetes, and other comorbidities. Investigating biomarkers and pathological processes linked to obesity is especially vital for young individuals, given their increased potential for lifestyle modifications. By comparing the genetic, proteomic, and metabolomic profiles of individuals categorized as underweight, normal, overweight, and obese, we aimed to determine which omics layer most accurately reflects the phenotypic changes in an organism that result from obesity. We profiled blood plasma samples by employing three omics methodologies. The untargeted GC×GC-MS metabolomics approach identified 313 metabolites. To augment the metabolomic dataset, we integrated a label-free HPLC-MS/MS proteomics method, leading to the identification of 708 proteins. The genomic layer encompassed the genotyping of 647,250 SNPs. Utilizing omics data, we trained sparse Partial Least Squares models to predict body mass index. Molecular features exhibiting frequently non-zero coefficients were selected as potential biomarkers, and we further explored enriched biological pathways. Proteomics was the most effective in single-omics analyses, with a median absolute error (MAE) of 5.44 ± 0.31 kg/m2, incorporating an average of 24 proteins per model. Metabolomics showed slightly lower performance (MAE = 6.06 ± 0.33 kg/m2), followed by genomics (MAE = 6.20 ± 0.34 kg/m2). As expected, multiomic models demonstrated better accuracy, particularly the combination of proteomics and metabolomics (MAE = 4.77 ± 0.33 kg/m2), while including genomics data did not enhance the results. This manuscript is the first multiomics study of obesity in a gender-balanced cohort of young adults profiled by genomic, proteomic, and metabolomic methods. The comprehensive approach provides novel insights into the molecular mechanisms of obesity, opening avenues for more targeted interventions.PMID:38666884 | DOI:10.3390/biology13040272