PubMed

Ecol Evol. 2024 Dec 22;14(12):e70751. doi: 10.1002/ece3.70751. eCollection 2024 Dec.ABSTRACTAnimal gut microbiota play important roles in host immunity, nutrient metabolism, and energy acquisition. The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health. Teratoscincus roborowskii is an endemic species which displays special frugivorous behavior, and it has been observed consuming grapes. To explore the effects of grape intake on the gut microbiota and metabolites of T. roborowskii, 16S rRNA sequencing and liquid chromatography mass spectrometry metabolomics were applied to investigate the gut microbiota and metabolite profiles of T. roborowskii fed with mealworms (LC group) and a mixture of mealworms and grapes (FG group). Our results demonstrated that a notable shift in microbiota composition occurred, particularly in terms of an increase in the probiotic Lactococcus in the FG group. The metabolite analysis revealed a significant enrichment of the pathways related to glucose metabolism in the FG group. In addition, the digestive enzyme activity analysis showed that the α-amylase and cellulase activities in the FG group were significantly higher than those of the LC group, which was consistent with the food type. A strong correlation between diet, gut microbiota, and fecal metabolites was observed, which may imply that different diets promote the establishment of host intestinal adaptation strategies. Our study provides a theoretical basis for host health and the scientific captive breeding of the desert lizards T. roborowskii.PMID:39717646 | PMC:PMC11663733 | DOI:10.1002/ece3.70751

Food Chem X. 2024 Dec 2;24:102063. doi: 10.1016/j.fochx.2024.102063. eCollection 2024 Dec 30.ABSTRACTNongxiangxing Baijiu is the most famous Baijiu flavor in China, and its characteristic style is closely related to Nongxiangxing Daqu used in fermentation. However, there are few reports about the difference of Daqu quality between seasonal variations. In this study, precipitation and temperature drove changes in microbial communities that resulted in differences in the flavor of Daqu produced in different seasons. For example, the average daily temperature in summer was as high as 27.29 ± 2.24 °C, which was significantly higher than other seasons (p < 0.01). Bacillus was abundant in the Daqu produced in this season, while tetramethylpyrazine flavor was more prominent, up to 1556.95 ± 153.92 μg/kg. Metabolomics studies identified major pathways associated with the weak flavor of spring_Daqu. In addition, LEFSe analysis revealed the marked microorganisms in different seasons. These results revealed the differences in seasonal Daqu, thus contributing to the scientific and rational use of Daqu.PMID:39717403 | PMC:PMC11665295 | DOI:10.1016/j.fochx.2024.102063

J Pharm Anal. 2024 Nov;14(11):101024. doi: 10.1016/j.jpha.2024.101024. Epub 2024 Jun 26.ABSTRACTTriclocarban (TCC) is a common antimicrobial agent that has been widely used in medical care. Given the close association between TCC treatment and metabolic disorders, we assessed whether long-term treatment to TCC at a human-relevant concentration could induce nephrotoxicity by disrupting the metabolic levels in a mouse model. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was applied to investigate the alterations in the spatial distributions and abundances of TCC, endogenous and exogenous metabolites in the kidney after TCC treatment. The results showed that TCC treatment induced the changes in the organ weight, organ coefficient and histopathology of the mouse kidney. MSI data revealed that TCC accumulated in all regions of the kidney, while its five metabolites mainly distributed in the cortex regions. The abundances of 79 biomolecules associated with pathways of leukotriene E4 metabolism, biosynthesis and degradation of glycerophospholipids and glycerolipids, ceramide-to-sphingomyelin signaling were significantly altered in the kidney after TCC treatment. These biomolecules showed distinctive distributions in the kidney and displayed a favorable spatial correlation with the pathological damage. This work offers new insights into the related mechanisms of TCC-induced nephrotocicity and exhibits the potential of MALDI-MSI-based spatial metabolomics as a promising approach for the risk assessment of agents in medical care.PMID:39717194 | PMC:PMC11664399 | DOI:10.1016/j.jpha.2024.101024

J Clin Hypertens (Greenwich). 2024 Dec 24. doi: 10.1111/jch.14961. Online ahead of print.ABSTRACTResistant hypertension (RH) may cause severe target organ damage and poses significant challenges in the field of hypertension prevention and treatment. Mining biological characteristics is crucial for exploring the pathogenesis of RH and for early diagnosis and treatment. Although several single-omics studies have been conducted on RH, its complex pathogenesis has only been partially elucidated. In this study, metabolomics, proteomics, and transcriptomics were jointly analyzed in healthy subjects and patients with hypertension and RH. The multi-omics analysis found that differential substances of RH were enriched in the HIF-1 signaling pathway and that differential substances such as ascorbic acid, reduced glutathione (GSH), choline, citric acid, transferrin receptor (TfR), Egl-9 family hypoxia-inducible factor 2 (EGLN2), and glutathione peroxidase 1 (GPX1) were screened out. The results of intergroup comparisons were as follows: RH versus N: ascorbic acid (Fold Change (FC):0.42, p < 0.01), GSH (FC:0.65, p < 0.05), choline (FC:1.32, p < 0.05), citric acid (FC:0.48, p < 0.001), TfR (FC2.32, p < 0.001), GPX1 (FC:16.02, p < 0.001), EGLN2 (FC:0.76, p < 0.001); RH versus EH: ascorbic acid (FC:0.52, p < 0.05), GSH (FC:0.55, p < 0.05), choline (FC:1.28, p < 0.05), citric acid (FC:0.59, p < 0.001), TfR (FC:1.71, p < 0.001), GPX1 (FC:2.11, p < 0.05), EGLN2 (FC:0.76, p < 0.05). These differential substances may reflect the biology of RH. This study provides multi-omics analysis for a deeper understanding of the complex molecular characteristics of RH, providing new insights into the pathogenesis, early diagnosis, and precise treatment of the disease.PMID:39716980 | DOI:10.1111/jch.14961

Brain. 2024 Dec 24:awae413. doi: 10.1093/brain/awae413. Online ahead of print.ABSTRACTConvergent data, across species, paint a compelling picture of the critical role of the gut and its resident microbiota in several brain functions and disorders. The chemicals mediating communication along these sophisticated highways of the brain-gut-microbiome (BGM) axis include both microbiota metabolites and classical neurotransmitters. Amongst the latter, GABA is fundamental to brain function where it mediates the majority of neuronal inhibition. Until recently, GABA's role and specific molecular targets in the periphery within the BGM axis had received limited attention. Yet, GABA is produced by neuronal and non-neuronal elements of the BGM, and recently GABA-modulating bacteria have been identified as key players in GABAergic gut systems, indicating that GABA-mediated signalling is likely to transcend not only physiological boundaries, but also species. We review available evidence with a view to better understand how GABA facilitates integration of molecularly and functionally disparate systems to bring about overall homeostasis, and how GABA perturbations within the BGM axis can give rise to multi-system medical disorders, thereby magnifying the disease burden and the challenges for patient care. Analysis of transcriptomic databases revealed significant overlaps between GABAAR subunits expressed in the human brain and gut. However, in the gut, there are notable expression profiles for a select number of subunits that have received limited attention to date but could be functionally relevant for BGM axis homeostasis. GABAergic signalling, via different receptor subtypes, directly regulates BGM homeostasis by modulating the excitability of neurons within brain centres responsible for gastrointestinal (GI) function, in a sex-dependent manner, potentially revealing mechanisms underlying the greater prevalence of GI disturbances in females. Apart from such top-down regulation of the BGM axis, a diverse group of cell types, including enteric neurons, glia, enteroendocrine cells, immune cells and bacteria - integrate peripheral GABA signals to influence brain functions and potentially contribute to brain disorders. We propose several priorities for this field, including the exploitation of available technologies to functionally dissect components of these GABA pathways within the BGM, with a GI and brain-behaviour-disease focus. Furthermore, in silico ligand-receptor docking analyses, using relevant bacterial metabolomic datasets, coupled with advances in knowledge of GABAAR 3D structures, could uncover new ligands with novel therapeutic potential. Finally, targeted design of dietary interventions is imperative to advance their therapeutic potential to support GABA homeostasis across the BGM axis.PMID:39716883 | DOI:10.1093/brain/awae413

Skelet Muscle. 2024 Dec 23;14(1):36. doi: 10.1186/s13395-024-00368-w.ABSTRACTDespite its notoriously mild phenotype, the dystrophin-deficient mdx mouse is the most common model of Duchenne muscular dystrophy (DMD). By mimicking a human DMD-associated metabolic comorbidity, hyperlipidemia, in mdx mice by inactivating the apolipoprotein E gene (mdx-ApoE) we previously reported severe myofiber damage exacerbation via histology with large fibro-fatty infiltrates and phenotype humanization with ambulation dysfunction when fed a cholesterol- and triglyceride-rich Western diet (mdx-ApoEW). Herein, we performed comparative lipidomic and metabolomic analyses of muscle, liver and serum samples from mdx and mdx-ApoEW mice using solution and high-resolution-magic angle spinning (HR-MAS) 1H-NMR spectroscopy. Compared to mdx and regular chow-fed mdx-ApoE mice, we observed an order of magnitude increase in lipid deposition in gastrocnemius muscle of mdx-ApoEW mice including 11-fold elevations in -CH3 and -CH2 lipids, along with pronounced elevations in serum cholesterol, fatty acid, triglyceride and phospholipids. Hepatic lipids were also elevated but did not correlate with the extent of muscle lipid infiltration or differences in serum lipids. This study provides the first lipometabolomic signature of severe mdx lesions exacerbated by high circulating lipids and lends credence to claims that the liver, the main regulator of whole-body lipoprotein metabolism, may play only a minor role in this process.PMID:39716324 | DOI:10.1186/s13395-024-00368-w

Arthritis Res Ther. 2024 Dec 23;26(1):227. doi: 10.1186/s13075-024-03429-z.ABSTRACTOBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory condition that, despite available approaches to manage the disease, lacks an efficient treatment and timely diagnosis. Using the most advanced omics technique, metabolomics and proteomics approach, we explored varied metabolites and proteins to identify unique metabolite-protein signatures involved in the disease pathogenesis of RA.METHODS: Untargeted metabolomics (n = 20) and proteomics (n = 60) of RA patients' plasma were carried out by HPLC/LC-MS/MS and SWATH, respectively and analyzed by Metaboanalyst. The targets of metabolite retrieved by PharmMapper were matched with SWATH data, and joint pathway analysis was carried out. An in-vitro study of metabolites in TNF-α induced SW982 cells was conducted by Western, RT-PCR, scratch, and ROS scavenging assay. The effect of GUDCA was also evaluated in the CIA rat model.RESULTS: A Total of 82 metabolites and 231 differential proteins were revealed. Porphyrin and chlorophyll pathway and its metabolite Glycoursodeoxycholic acid (GUDCA) was found to be significantly altered. In vitro analysis has shown that GUDCA reduces inflammation thus offering protection against ROS production and cell proliferation. PharmMapper analysis revealed that GUDCA was significantly linked with identified SWATH proteins insulin like growth factor-1(IGF1), and Transthyretin (TTR) and it upregulates the expression of IGF1 and downregulates the expression of TTR in both in vitro and in vivo models.CONCLUSION: GUDCA was found to possess antioxidative, antiproliferative properties and an effective anti-inflammatory property at a low dosage. It may be considered as a potential therapeutic option for reducing the inflammatory parameters associated with RA.PMID:39716302 | DOI:10.1186/s13075-024-03429-z

J Transl Med. 2024 Dec 23;22(1):1138. doi: 10.1186/s12967-024-05955-5.ABSTRACTBACKGROUND: Scutellaria baicalensis Georgi, a traditional Chinese herb, is known for its various biological effects, including antibacterial, anti-inflammatory, antioxidative, and antitumor properties. However, the function and mechanisms of methanol extract of Scutellaria baicalensis Georgi (MESB) in treating hepatic fibrosis remain unclear.METHODS: This study utilized a CCl4-induced mouse model of hepatic fibrosis to assess the effects of MESB through histopathological analysis and serum tests. The anti-fibrosis mechanism of MESB was investigated using qPCR, Western blotting, RNA interference, proteomics, and metabolomics. Spatial metabolomics identified key components of MESB in liver tissue, while molecular docking determined their targets.RESULTS: Treatment with MESB alleviated hepatic pathological changes and reversed hepatic fibrosis in the CCl4-induced models, as evidenced by decreased collagen fibers deposition, reduced expression of hepatic fibrosis markers COL1A1, FN, and PAI-1, and lowered serum levels of AST and ALT. In vitro, MESB inhibited the proliferation of LX-2 cells and the expression of hepatic fibrosis markers. Furthermore, MESB intervention modulated various pathways, particularly those involved in metabolic pathways. Subsequent metabolomics analysis demonstrated that MESB disrupted glycerophospholipid metabolism and suppressed arachidonic acid metabolism. MESB downregulated the expression of cPLA2 in LX-2 cells, leading to decreased production of arachidonic acid and its downstream inflammatory mediators. Meanwhile, MESB inhibited the expression of cPLA2 and its downstream NF-κB pathway in the liver tissues of models induced by CCl4. Additionally, silencing cPLA2 markedly reduced the expressions of COL1A1, FN, and PAI-1. Spatial metabolomics analysis confirmed the penetration of baicalein, wogonin and wogonoside into liver tissue. Further results indicated that baicalein and wogonin inhibited the expression of cPLA2, while baicalin and wogonoside do not exhibit this effect. Moreover, molecular docking suggested that baicalein and wogonin possess the potential to directly interact with cPLA2.CONCLUSION: This study reveals that MESB is crucial in preventing hepatic fibrosis via the cPLA2-mediated arachidonic acid metabolic pathway, highlighting its key active components as potential drugs for fibrosis treatment.PMID:39716274 | DOI:10.1186/s12967-024-05955-5

Crit Care. 2024 Dec 24;28(1):431. doi: 10.1186/s13054-024-05216-3.ABSTRACTBACKGROUND: Lipids play a critical role in defense against sepsis. We sought to investigate gene expression and lipidomic patterns of lipid dysregulation in sepsis.METHODS: Data from four adult sepsis studies were analyzed and findings were investigated in two external datasets. Previously characterized lipid dysregulation subphenotypes of hypolipoprotein (HYPO; low lipoproteins, increased mortality) and normolipoprotein (NORMO; higher lipoproteins, lower mortality) were studied. Leukocytes collected within 24 h of sepsis underwent RNA sequencing (RNAseq) and shotgun plasma lipidomics was performed.RESULTS: Of 288 included patients, 43% were HYPO and 57% were NORMO. HYPO patients exhibited higher median SOFA scores (9 vs 5, p = < 0.001), vasopressor use (67% vs 34%, p = < 0.001), and 28-day mortality (30% vs 16%, p = 0.004). Leukocyte RNAseq identified seven upregulated lipid metabolism genes in HYPO (PCSK9, DHCR7, LDLR, ALOX5, PLTP, FDFT1, and MSMO1) vs. NORMO patients. Lipidomics revealed lower cholesterol esters (CE, adjusted p = < 0.001), lysophosphatidylcholines (LPC, adjusted p = 0.001), and sphingomyelins (SM, adjusted p = < 0.001) in HYPO patients. In HYPO patients, DHCR7 expression strongly correlated with reductions in CE, LPC, and SM (p < 0.01), while PCSK9, MSMO1, DHCR7, PLTP, and LDLR upregulation were correlated with low LPC (p < 0.05). DHCR7, ALOX5, and LDLR correlated with reductions in SM (p < 0.05). Mortality and phenotype comparisons in two external datasets (N = 824 combined patients) corroborated six of the seven upregulated lipid genes (PCSK9, DHCR7, ALOX5, PLTP, LDLR, and MSMO1).CONCLUSION: We identified a genetic lipid dysregulation signature characterized by seven lipid metabolism genes. Five genes in HYPO sepsis patients most strongly correlated with low CE, LPC, and SMs that mediate cholesterol storage and innate immunity.PMID:39716214 | DOI:10.1186/s13054-024-05216-3

BMC Psychiatry. 2024 Dec 23;24(1):946. doi: 10.1186/s12888-024-06413-8.ABSTRACTBACKGROUND: Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic drugs and may lead to cardiometabolic comorbidities. There is an urgent public health need to identify patients at high risk of AIWG and determine potential biomarkers for AIWG.METHODS: In the Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) trail, first-episode schizophrenia patients were randomly assigned to olanzapine, risperidone, perphenazine, amisulpride or aripiprazole for 8 weeks. We applied absolute quantitative lipidomics at baseline and after 8 weeks of antipsychotic treatment in 80 patients. To evaluate the effects of AIWG on lipid profile, 25 patients with ≥ 7% weight changes (weight gain, WG) and 28 patients with <|3|% weight changes (weight stable, WS) were investigated, separately.RESULTS: We found that baseline CerP(d40:3) and PC(20:1_22:6) were positively associated with weight changes at follow-up (r > 0.4, pFDR < 0.05). Additionally, baseline CerP(d40:3) and PC(20:1_22:6) independently predicted rapid weight gain, with receiver operating curve (ROC) of 0.76 (95% CI: 0.63-0.90), and 0.75 (95% CI: 0.62-0.88), respectively. Compared with baseline, levels of 45 differential lipid metabolites (fold change > 1.2, VIP > 1 and pFDR < 0.05) were significantly higher in the WG group. Interestingly, no differential lipid metabolites were identified in the WS group. The LASSO regression model identified 18 AIWG lipid signatures, including 2 cholesterol esters (ChEs), 1 diglyceride (DG), 12 phosphatidylcholines (PCs), 1 phosphatidylglycerol (PG), 1 phosphatidylinositol (PI), and 1 sphingomyelin (SM), with the ChE(16:1) contributing the most. Furthermore, the level changes of ChE(16:1) were positively associated with weight gain(r = 0.67, pFDR < 0.05).CONCLUSION: Our findings indicate that lipid profile may serve as predictors of rapid weight gain in schizophrenia and provide useful markers for AIWG intervention.PMID:39716136 | DOI:10.1186/s12888-024-06413-8

BMC Pregnancy Childbirth. 2024 Dec 24;24(1):856. doi: 10.1186/s12884-024-07065-y.ABSTRACTOBJECTIVE: This study aimed to detect the proteins and metabolites in the cervicovaginal fluid to observe their relationship with the occurrence of placenta accreta spectrum and the potential biomarkers with predictive value.METHODS: Cervicovaginal fluid samples were collected before delivery from 6 participants of PAS and 6 controls subjects with similar gestational ages. The severity of PAS was evaluated by ultrasound and MRI scoring system and confirmed by the intraoperative findings or pathological examination. We used 4D label-free quantitative proteomics and untargeted metabolomics to identify the proteins and metabolites in cervicovaginal fluid, and analyzed the functions of differential expressed proteins or metabolites in PAS by multi-omics combined with bioinformatics analysis.RESULTS: Proteomics and metabolomics screened 127 and 12 differential expressed proteins and metabolites in CVF of PAS, respectively. Proteins and metabolites that significantly dysregulated in participants with placenta accreta spectrum were factors that regulate angiogenesis, and extracellular matrix proteins that regulate trophoblast invasion. Among them, the important difference expressed proteins/metabolites with representative significance are arginine, GAL7, uPA, MMP9 and ITGAM, that may be useful as potential biomarkers for the prediction and early diagnosis of PAS.CONCLUSION: Cervicovaginal fluid in patients with PAS presents a protein-metabolic microenvironment that promotes trophoblast invasion, endothelial activation and vascular proliferation.PMID:39716114 | DOI:10.1186/s12884-024-07065-y

BMC Genomics. 2024 Dec 23;25(1):1239. doi: 10.1186/s12864-024-11142-z.ABSTRACTCastration is widely used in poultry and livestock to enhance fat metabolism and improve the flavor, tenderness and juiciness of meat. However, the genetic regulatory mechanism underlying castration consequences have not been clarified. To investigate the key metabolites affecting the quality of capons and the key regulatory mechanisms, Qingyuan partridge roosters were subjected to castration. Metabolic profiling was used to detect differential metabolites in the breast muscle of both capon and control groups. Additionally, an integrative analysis of transcriptomics and proteomics was conducted to explore the genetic regulation mechanisms influencing meat quality. The results indicated that the muscle fiber density and shear force of capons was lower than that of normal chickens, and the fat percentage of capon group (CAM) was higher than control group (COM). The expression of the metabolite inostine-5'-monophosphate (IMP) was lower in capons, and lipid metabolites (PC (10:0/10:0), PC (6:0/13:1), LPC 22:6, LPC 18:2, LPE 18:1, LPE 20:4) were higher in capons. Metabolic pathways were found to be a common signaling pathway in all omics. Glutamate-ammonia ligase (GLUL), acetyl-CoA carboxylase beta (ACACB), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), 4-hydroxy-2-oxoglutarate aldolase 1 (HOGA1) and glutathione S-transferase alpha 2 (GSTA2) regulate the expression of citric acid, arachidonic acid, palmitic acid, isocitric acid, and betaine. These findings highlight the key mechanisms contributing to the meat quality differences between capons and normal chickens.PMID:39716077 | DOI:10.1186/s12864-024-11142-z

Methods Mol Biol. 2025;2884:81-98. doi: 10.1007/978-1-0716-4298-6_7.ABSTRACTShotgun proteomics can be applied to identify and study insect species in diverse research areas such as agriculture, forensics, biodiversity conservation, and food safety. In this chapter, we have provided a detailed protocol for shotgun proteomics analytical methods involving enzymatic digestion of insect proteins using trypsin, separation using high-performance liquid chromatography, and detection of separated peptides using high-resolution mass spectrometry. The protocol also covers the utilization of bioinformatics software for protein identification and spectral library building, proposing both proteomic database-dependent and independent methods. This chapter provides a valuable foundation for applying insect proteomics by discussing a step-by-step protocol.PMID:39715999 | DOI:10.1007/978-1-0716-4298-6_7

Nature. 2024 Dec 23. doi: 10.1038/s41586-024-08555-x. Online ahead of print.NO ABSTRACTPMID:39715925 | DOI:10.1038/s41586-024-08555-x

NPJ Vaccines. 2024 Dec 23;9(1):255. doi: 10.1038/s41541-024-01042-4.ABSTRACTFiloviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.S. adults and evaluated the safety, reactogenicity and immunogenicity of homologous and heterologous MVA-BN®-Filo and Ad26.ZEBOV prime-boost schedules followed in select arms by MVA-BN®-Filo boost at 1 year (NCT02891980). We found that all vaccine regimens had acceptable safety and reactogenicity. The heterologous prime-boost strategy elicited superior Ebola binding and neutralizing antibody, antibody-dependent cellular cytotoxicity (ADCC), and cellular responses compared to homologous prime-boost. The MVA-BN®-Filo boost administered at 1 year resulted in robust humoral and cellular responses that persisted through 6-month follow-up. Overall, our data demonstrated that a heterologous Ad26.ZEBOV/MVA-BN®-Filo prime-boost was safe and immunogenic and established immunologic memory primed to respond after re-exposure. Clinicaltrials.gov, NCT02891980, registered September 1, 2016.PMID:39715748 | DOI:10.1038/s41541-024-01042-4

PLoS One. 2024 Dec 23;19(12):e0314599. doi: 10.1371/journal.pone.0314599. eCollection 2024.ABSTRACTBACKGROUND: Chronic prostatitis may be a risk factor for developing proliferative changes in the prostate, although the underlying mechanisms are not entirely comprehended.MATERIALS AND METHODS: Fifty individual prostate tissues were examined in this study, consisting of 25 patients diagnosed with prostatic hyperplasia combined with histologic chronic inflammation and 25 patients diagnosed with prostatic hyperplasia alone. We employed UPLC-Q-TOF-MS-based untargeted metabolomics using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to identify differential metabolites that can reveal the mechanisms that underlie the promotion of prostate hyperplasia by histologic chronic inflammation. Selected differential endogenous metabolites were analyzed using bioinformatics and subjected to metabolic pathway studies.RESULTS: Nineteen differential metabolites, consisting of nine up-regulated and ten down-regulated, were identified between the two groups of patients. These groups included individuals with combined histologic chronic inflammation and those with prostatic hyperplasia alone. Glycerolipids, glycerophospholipids, and sphingolipids were primarily the components present. Metabolic pathway enrichment was conducted on the identified differentially expressed metabolites. Topological pathway analysis revealed the differential metabolites' predominant involvement in sphingolipid, ether lipid, and glycerophospholipid metabolism. The metabolites involved in sphingolipid metabolism were Sphingosine, Cer (d18:1/24:1), and Phytosphingosine. The metabolites involved in ether lipid metabolism were Glycerophosphocholine and LysoPC (O-18:0/0:0). The metabolites involved in glycerophospholipid metabolism were LysoPC (P-18:0/0:0) and Glycerophosphocholine. with Impact > 0. 1 and FDR < 0. 05, the most important metabolic pathway was sphingolipid metabolism.CONCLUSIONS: In conclusion, our findings suggest that patients with prostate hyperplasia and combined histologic chronic inflammation possess distinctive metabolic profiles. These differential metabolites appear to play a significant role in the pathogenesis of histologic chronic inflammation-induced prostate hyperplasia, primarily through the regulation of sphingolipids and glycerophospholipids metabolic pathways. The mechanism by which histologic chronic inflammation promotes prostate hyperplasia was elucidated through the analysis of small molecule metabolites. These findings support the notion that chronic prostatitis may contribute to an increased risk of prostate hyperplasia.PMID:39715183 | DOI:10.1371/journal.pone.0314599

J Proteome Res. 2024 Dec 23. doi: 10.1021/acs.jproteome.4c00410. Online ahead of print.ABSTRACTThe identification of peptides is a cornerstone of mass spectrometry-based proteomics. Spectral library-based algorithms are well-established methods to enhance the identification efficiency of peptides during database searches in proteomics. However, these algorithms are not specifically tailored for tandem mass tag (TMT)-based proteomics due to the lack of high-quality TMT spectral libraries. Here, we introduce JUMPlib, a computational tool for a TMT-based spectral library search. JUMPlib comprises components for generating spectral libraries, conducting library searches, filtering peptide identifications, and quantifying peptides and proteins. Fragment ion indexing in the libraries increases the search speed and utilizing the experimental retention time of precursor ions improves peptide identification. We found that methionine oxidation is a major factor contributing to large shifts in peptide retention time. To test the JUMPlib program, we curated two comprehensive human libraries for the labeling of TMT6/10/11 and TMT16/18 reagents, with ∼286,000 precursor ions and ∼304,000 precursor ions, respectively. Our analyses demonstrate that JUMPlib, employing the fragment ion index strategy, enhances search speed and exhibits high sensitivity and specificity, achieving approximately a 25% increase in peptide-spectrum matches compared to other search tools. Overall, JUMPlib serves as a streamlined computational platform designed to enhance peptide identification in TMT-based proteomics. Both the JUMPlib source code and libraries are publicly available.PMID:39715016 | DOI:10.1021/acs.jproteome.4c00410

Chembiochem. 2024 Dec 23:e202400852. doi: 10.1002/cbic.202400852. Online ahead of print.ABSTRACTThe importance of the protein-metabolite interaction network extends beyond its relevance to life sciences focused on proteins, it also profoundly influences its mechanisms related to disease targets, drug screening, and clinical diagnosis and treatment. Research methods targeting protein-metabolite interaction focus on enhancing the detectable signals of specific interactions by examining the structural characteristics of both proteins and metabolites in conjunction with chemical molecules, playing a crucial role in elucidating the protein-metabolite interaction network. Consequently, this article outlines several chemical targeting strategies developed in recent years and provides examples of their applications in the discovery and interpretation of new protein-metabolite interaction pathways. Finally, a brief summary will be presented regarding technological advances, research prospects, and current challenges of protein-metabolite interaction research.PMID:39715006 | DOI:10.1002/cbic.202400852

Mol Biotechnol. 2024 Dec 23. doi: 10.1007/s12033-024-01346-9. Online ahead of print.ABSTRACTStaphylococcus warneri is a gram-positive mesophilic bacterium, resilient to extreme environmental conditions. To unravel its Osmotic Tolerance Response (OTR), we conducted proteomic and metabolomic analyses under drought (PEG) and salt (NaCl) stresses. Our findings revealed 1340 differentially expressed proteins (DEPs) across all treatments. Interestingly, majority of these DEPs were part of common pathways activated by S. warneri. CPD1 in response to osmotic stress. Notably, the bacterial isolate exhibited increased expression of lysophospholipases associated with biofilm formation and protection from environmental stresses, transglycosylases involved in peptidoglycan biosynthesis, and acetoin reductase linked to acetoin metabolism. The upregulation of global ion transporters, including ABC transporters, potassium ion transport, and glutamate transport, indicated the bacterium's ability to maintain ionic balance under stress conditions. Protein-protein docking analysis revealed highest interactions with thioredoxin and alpha-acetolactate decarboxylase, highlighting their crucial roles in the mechanisms of osmotic stress tolerance in S. warneri CPD1. Metabolomic results demonstrated significant alterations in fatty acids and amino acids. In the greenhouse experiment, the bacterial isolate significantly enhanced wheat biomass, nutrient content, photosynthesis, and proline levels under stress conditions, making it a promising bacterial inoculant and biostimulant for improving crop productivity in challenging environments.PMID:39714746 | DOI:10.1007/s12033-024-01346-9

Anal Bioanal Chem. 2024 Dec 23. doi: 10.1007/s00216-024-05706-x. Online ahead of print.ABSTRACTCoronavirus disease 2019 is a highly contagious respiratory illness caused by the coronavirus SARS-CoV-2. Symptoms can range from mild to severe and typically appear 2-14 days after virus exposure. While vaccination has significantly reduced the incidence of severe complications, strategies for the identification of new biomarkers to assess disease severity remains a critical area of research. Severity biomarkers are essential for personalizing treatment strategies and improving patient outcomes. This study aimed to identify sex-specific biomarkers for COVID-19 severity in a Chilean population (n = 123 female, n = 115 male), categorized as control, mild, moderate, or severe. Data were collected using clinical biochemistry parameters and mass spectrometry-based metabolomics and lipidomics to detect alterations in plasma cytokines, metabolites, and lipid profiles related to disease severity. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to select significant characteristic features for each group. The results revealed distinct biomarkers for males and females. In males, COVID-19 severity of was associated with inflammation parameters, triglycerides content, and phospholipids profiles. For females, liver damage parameters, triglycerides content, cholesterol derivatives, and phosphatidylcholine were identified as severity biomarkers. For both sexes, most of the biomarker combinations evaluated got areas under the ROC curve greater than 0.8 and low prediction errors. These findings suggest that sex-specific biomarkers can help differentiate the levels of COVID-19 severity, potentially aiding in the development of tailored treatment approaches.PMID:39714519 | DOI:10.1007/s00216-024-05706-x