PubMed

Br J Pharmacol. 2024 Jul 27. doi: 10.1111/bph.16469. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Acute pancreatitis (AP) is associated with acinar cell death and inflammatory responses. Ferroptosis is characterized by an overwhelming lipid peroxidation downstream of metabolic dysfunction, in which NADPH-related redox systems have been recognized as the mainstay in ferroptosis control. Nevertheless, it remains unknown how ferroptosis is regulated in AP and whether we can target it to restrict AP development.EXPERIMENTAL APPROACH: Metabolomics were applied to explore changes in metabolic pathways in pancreatic acinar cells (PACs) in AP. Using wild-type and Ptf1aCreERT2/+IDH2fl/fl mice, AP was induced by caerulein and sodium taurocholate (NaT). IDH2 overexpressing adenovirus was constructed for infection of PACs. Mice or PACs were pretreated with inhibitors of FSP1 or glutathione reductase. Pancreatitis severity, acinar cell injury, mitochondrial morphological changes and pancreatic lipid peroxidation were analysed.KEY RESULTS: Unsaturated fatty acid biosynthesis and the tricarboxylic acid cycle pathways were significantly altered in PACs during AP. Inhibition of ferroptosis reduced mitochondrial damage, lipid peroxidation and the severity of AP. During AP, the NADPH abundance and IDH2 expression were decreased. Acinar cell-specific deletion of IDH2 exacerbated acinar cell ferroptosis and pancreatic injury. Pharmacological inhibition of NADPH-dependent GSH/GPX4 and FSP1/CoQ10 pathways abolished the protective effect of IDH2 overexpression on ferroptosis in acinar cells. CoQ10 supplementation attenuated experimental pancreatitis via inhibiting acinar cell ferroptosis.CONCLUSION AND IMPLICATIONS: We identified the IDH2-NADPH pathway as a novel regulator in protecting against AP via restricting acinar cell ferroptosis. Targeting the pathway and its downstream may shed light on AP treatment.PMID:39072736 | DOI:10.1111/bph.16469

Appl Environ Microbiol. 2024 Jul 29:e0036024. doi: 10.1128/aem.00360-24. Online ahead of print.ABSTRACTCandida albicans, an opportunistic oral pathogen, synergizes with Staphylococcus aureus, allowing bacteria to co-invade and systemically disseminate within the host. Studying human-microbe interactions creates the need for a universal culture medium that supports fungal, bacterial, and human cell culturing, while allowing sensitive analytical approaches such as OMICs and chromatography techniques. In this study, we established a fully defined, customizable adaptation of Dulbecco's modified Eagle medium (DMEM), allowing multi-kingdom culturing of S. aureus, C. albicans, and human oral cell lines, whereas minimal version of DMEM (mDMEM) did not support growth of S. aureus, and neither did supplementation with dextrose, MEM non-essential amino acids, pyruvate, and Glutamax. This new medium composition, designated as "mDMEM-DMP," promoted growth of all tested S. aureus strains. Addition of 25 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) further improved growth, while higher concentrations did not improve growth any further. Higher concentrations of HEPES did result in prolonged stabilization of medium pH. mDMEM-DMP promoted (hyphal) C. albicans monoculturing and co-culturing on both solid and semi-solid surfaces. In contrast to S. aureus, addition of HEPES reduced C. albicans maximum culture optical density (OD). Finally, only buffered mDMEM-DMP (100 mM HEPES) was successful in maintaining the metabolic activity of human oral Ca9-22 and HO1N1 cell lines for 24 hours. Altogether, our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions.IMPORTANCE: Interaction between microbes and the host are in the center of interest both in disease and in health. In order to study the interactions between microbes of different kingdoms and the host, alternative media are required. Synthetic media are useful as they allow addition of specific components. In addition, well-defined media are required if high-resolution analyses such as metabolomics and proteomics are desired. We describe the development of a synthetic medium to study the interactions between C. albicans, S. aureus, and human oral epithelial cells. Our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions.PMID:39072650 | DOI:10.1128/aem.00360-24

Virulence. 2024 Dec;15(1):2384563. doi: 10.1080/21505594.2024.2384563. Epub 2024 Jul 29.ABSTRACTPhenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.PMID:39072499 | DOI:10.1080/21505594.2024.2384563

ACS Chem Neurosci. 2024 Jul 29. doi: 10.1021/acschemneuro.4c00199. Online ahead of print.ABSTRACTIn an era when population aging is increasing the burden of neurodegenerative conditions, deciphering the mechanisms underlying brain senescence is more important than ever. Here, we present a spatial metabolomics analysis of age-induced neurochemical alterations in the mouse brain using negative ionization mode mass spectrometry imaging. The age-dependent effects of the acetylcholinesterase inhibitor tacrine were simultaneously examined. For ultrahigh mass resolution analysis, we utilized a Fourier-transform ion cyclotron resonance spectrometer. To complement this, a trapped ion mobility spectrometry time-of-flight analyzer provided high speed and lateral resolution. The chosen approach facilitated the detection and identification of a wide range of metabolites, from amino acids to sphingolipids. We reported significant, age-dependent alterations in brain lipids which were most evident for sulfatides and lysophosphatidic acids. Sulfatide species, which are mainly localized to white matter, either increased or decreased with age, depending on the carbon chain length and hydroxylation stage. Lysophosphatidic acids were found to decrease with age in the detailed cortical and hippocampal subregions. An age-dependent increase in the glutamine/glutamate ratio, an indicator of glia-neuron interconnection and neurotoxicity, was detected after tacrine administration. The presented metabolic mapping approach was able to provide visualizations of the lipid signaling and neurotransmission alterations induced by early aging and can thus be beneficial to further elucidating age-related neurochemical pathways.PMID:39072364 | DOI:10.1021/acschemneuro.4c00199

Front Immunol. 2024 Jul 12;15:1414476. doi: 10.3389/fimmu.2024.1414476. eCollection 2024.ABSTRACTThe early and accurate identification of predictive biomarkers for antiviral treatment efficacy remains a significant clinical challenge, particularly in the management of chronic hepatitis B (CHB). This study aimed to assess whether the plasma metabolome could reliably predict the success of antiviral therapy in CHB patients. We conducted a retrospective analysis on 56 treatment-naive CHB patients at the First Affiliated Hospital of Zhejiang University from December 2013 to March 2016. Patients who underwent a 48-week treatment regimen of entecavir (ETV) and interferon-alpha (IFN-α) were randomly assigned to either a discovery cohort (n=29) or a validation cohort (n=27). Based on the outcome of the treatment, patients were classified as HBeAg seroconversion group (High responders, Hrp) or the non-remission group (Low responder, Lrp). Our methodology involved an untargeted analysis of the amine/phenol and carboxylic acid submetabolomes in the CHB patients under treatment, utilizing chemical isotope labeling (CIL) techniques with liquid chromatography-mass spectrometry (LC-MS). Several metabolites were identified as having significant diagnostic potential for distinguishing Hrp from Lrp, with areas under the receiver operating characteristic curve (AUC) exceeding those typical clinical indicators. Notably, four metabolites, namely 2-methyl-3-ketovaleric acid, 2-ketohexanoic acid, 6-oxo-1,4,5,6-tetrahydronicotinic acid, and α-ketoisovaleric acid, demonstrated exceptionally high sensitivity and specificity in both cohorts, nearing 100%. In contrast, the clinical indicators, including HBcAb, log(HBsAg), and HBeAb, demonstrated lower and inconsistent sensitivity and specificity between the discovery and validation cohorts. Using HBcAb as a marker, the sensitivity was 87.5% with 76.9% specificity in the discovery cohort; however, the sensitivity dropped to 46.7% with 91.7% specificity in the validation cohort. Using log(HBsAg), the sensitivity was 84.6% with 69.2% specificity in the discovery cohort, compared to 85.7% sensitivity and 83.3% specificity in the validation cohort. For HBeAb, the separation of Hrp and Lrp had a sensitivity of 87.5% with 69.2% specificity in the discovery cohort, while the validation cohort showed 86.7% sensitivity and 91.7% specificity.PMID:39072321 | PMC:PMC11272971 | DOI:10.3389/fimmu.2024.1414476

Chin Herb Med. 2024 Jan 29;16(3):435-448. doi: 10.1016/j.chmed.2023.10.004. eCollection 2024 Jul.ABSTRACTOBJECTIVE: Lilium brownii var. viridulum (LB) and L. lancifolium (LL) are the main sources of medicinal lily (Lilii Bulbus, Baihe in Chinese) in China. However, the functional components of these two species responsible for the treatment efficacy are yet not clear. In order to explore the therapeutic material basis of Lilii Bulbus, we selected L. davidii var. willmottiae (LD) only used for food as the control group to analyze the differences between LD and the other two (LB and LL).METHODS: Metabolome and transcriptome were carried out to investigate the differences of active components in LD vs LB and LD vs LL. Data of metabolome and transcriptome was analysed using various analysis methods, such as principal component analysis (PCA), hierarchical cluster analysis (HCA), and so on. Differentially expressed genes (DEGs) were enriched through KEGG and GO enrichment analysis.RESULTS: The PCA and HCA of the metabolome indicated the metabolites were clearly separated and varied greatly in LL and LB contrasted with LD. There were 318 significantly differential metabolites (SDMs) in LD vs LB group and 298 SDMs in LD vs LL group. Compared with LD group, the significant up-regulation of steroidal saponins and steroidal alkaloids were detected both in LB and LL groups, especially in LB group. The HCA of transcriptome indicated that there was significant difference in LB vs LD group, while the difference between LL and LD varied slightly. Additionally, 47 540 DEGs in LD vs LB group and 18 958 DEGs in LD vs LL group were identified. Notably, CYP450s involving in the biosynthesis of steroidal saponins and steroidal alkaloids were detected, and comparing with LD, CYP724, CYP710A, and CYP734A1 in LB and CYP90B in LL were all up-regulated.CONCLUSION: This study suggested that steroidal saponins and steroidal alkaloids maybe the representative functional components of Lilii Bulbus, which can provide new insights for Lilii Bulbus used in the research and development of classic famous formula.PMID:39072198 | PMC:PMC11283230 | DOI:10.1016/j.chmed.2023.10.004

medRxiv [Preprint]. 2024 Jul 21:2024.07.19.24310722. doi: 10.1101/2024.07.19.24310722.ABSTRACTImmigrants from less industrialized countries who are living in the U.S. often bear an elevated risk of multiple disease due to the adoption of a U.S. lifestyle. Blood metabolome holds valuable information on environmental exposure and the pathogenesis of chronic diseases, offering insights into the link between environmental factors and disease burden. Analyzing 634 serum metabolites from 7,114 Hispanics (1,141 U.S.-born, 5,973 foreign-born) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we identified profound blood metabolic shift during acculturation. Machine learning highlighted the prominent role of non-genetic factors, especially food and gut microbiota, in these changes. Immigration-related metabolites correlated with plant-based foods and beneficial gut bacteria for foreign-born Hispanics, and with meat-based or processed food and unfavorable gut bacteria for U.S.-born Hispanics. Cardiometabolic traits, liver, and kidney function exhibited a link with immigration-related metabolic changes, which were also linked to increased risk of diabetes, severe obesity, chronic kidney disease, and asthma.HIGHLIGHTS: A substantial proportion of identified blood metabolites differ between U.S.-born and foreign-born Hispanics/Latinos in the U.S.Food and gut microbiota are the major modifiable contributors to blood metabolomic difference between U.S.-born and foreign-born Hispanics/Latinos.U.S. nativity related metabolites collectively correlate with a spectrum of clinical traits and chronic diseases.PMID:39072018 | PMC:PMC11275661 | DOI:10.1101/2024.07.19.24310722

Mol Clin Oncol. 2024 Jul 9;21(3):62. doi: 10.3892/mco.2024.2760. eCollection 2024 Sep.ABSTRACTVolumetric-modulated arc therapy (VMAT) is a radiotherapy technique used to treat patients with localized prostate cancer, which is frequently associated with acute adverse events (AEs) that can affect subsequent treatment. Notably, the radiation dose of VMAT can be tailored to each patient. In the present study, a retrospective analysis was performed to predict acute AEs in response to a therapeutic high radiation dose rate based on urinary metabolomic molecules, which are easily collected as noninvasive biosamples. Urine samples from 11 patients with prostate cancer who were treated with VMAT (76 Gy/38 fractions) were collected. The study found that seven patients (~64%) exhibited genitourinary toxicity (Grade 1) and four patients had no AEs. A total of 630 urinary metabolites were then analyzed using a mass spectrometer (QTRAP6500+; AB SCIEX), and 234 relevant molecules for biological and clinical applications were extracted from the absolute quantified metabolite values using the MetaboINDICATOR tool. In the Grade 1 acute AE group, there was a significant negative correlation (rs=-0.297, P<0.05) between the number of VMAT fractions and total phospholipase A2 activity in the urine. Additionally, patients with Grade 1 AEs exhibited a decrease in PC aa C40:1, a phospholipid. These findings suggested that specific lipids found in urinary metabolites may serve as predictive biomarkers for acute AEs in response to external radiotherapy.PMID:39071973 | PMC:PMC11273245 | DOI:10.3892/mco.2024.2760

Food Chem X. 2024 Mar 31;23:101331. doi: 10.1016/j.fochx.2024.101331. eCollection 2024 Oct 30.ABSTRACTTo investigate the correlation between the difference of secondary metabolites and the disease-resistance activity of different varieties of Congou black tea. Among a total of 657 secondary metabolites identified, 183 metabolites had anti-disease activity, 113 were key active ingredients in traditional Chinese medicine (TCM), 73.22% had multiple anti-disease activities, and all were mainly flavonoids and phenolic acids. The main enriched metabolic pathways were phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, flavonoid biosynthesis, and metabolic pathways. Flavonoid and phenolic acid secondary metabolites were more correlated with anti-disease activity and key active TCM ingredients. Conclusion: The types of JGY and Q601 Congou black tea of the relative contents show large differences in secondary metabolites. Flavonoid and phenolic acid secondary metabolites were identified as the primary factors contributing to the variation in secondary metabolites among different varieties of Congou black tea. These compounds also exhibited a stronger correlation with disease resistance activity.PMID:39071939 | PMC:PMC11282962 | DOI:10.1016/j.fochx.2024.101331

Food Chem X. 2024 Jul 2;23:101610. doi: 10.1016/j.fochx.2024.101610. eCollection 2024 Oct 30.ABSTRACTDietary fiber targets the regulation of the intestinal flora and thus affects host health, however, the complex relationship between these factors lacks direct evidence. In this study, the regulatory effects of Konjac glucomannan (KGM) on key metabolites of host intestinal flora were examined by using in vitro fermentation. The results showed that KGM could be utilized by the intestinal flora, which inhibited the relative abundance of Paeniclostridium, Lachnoclostridium, Phascolarctobacterium, and Bacteroides and enriched the relative abundance of Desulfovibrio, Sutterella, etc. Fermentation is accompanied by the production of short-chain acids, including acetic and propionic acids. Metabolomics revealed that KGM significantly promoted amino acid metabolism, lipid metabolism, and the biosynthesis of other secondary metabolites. Correlation analysis results showed that the increase of panose and N-(1-carboxy-3-carboxanilidopropyl) alanylproline content was positively correlated with the relative abundance of Megamonas. These results provide evidence that KGM affects host health by regulating gut microbiota and its metabolites.PMID:39071938 | PMC:PMC11282934 | DOI:10.1016/j.fochx.2024.101610

Food Chem X. 2024 Jun 27;23:101595. doi: 10.1016/j.fochx.2024.101595. eCollection 2024 Oct 30.ABSTRACTThe harvest date is a crucial factor in determining tea quality. For Lu'an Guapian (LAGP) tea, Grain Rain period (GRP) represents a pivotal phase in the transformation of tea quality. The sensory evaluation, computer vision and E-tongue revealed that the liquor color score, B and G values of tea infusion were increased during GRP, while the astringency, bitterness intensities and the R value of the tea infusion were decreased. Consequently, the tea infusion exhibited a greener hue and the taste became appropriate during GRP. Non-targeted metabolomics revealed that the majority of amino acids and derivatives was reduced during GRP. Furthermore, flavonoids, in particular flavonol glycosides, exhibited considerable variation during GRP. Finally, nine metabolites were identified as markers for quality transformation during GRP by PLS and Random Forest. This study investigated the quality of LAGP teas during GRP and filled the gap in the variation of LAGP tea quality during GRP.PMID:39071934 | PMC:PMC11283131 | DOI:10.1016/j.fochx.2024.101595

Food Chem X. 2024 Jul 2;23:101607. doi: 10.1016/j.fochx.2024.101607. eCollection 2024 Oct 30.ABSTRACTTwo untargeted metabolomics approaches (LC-HRMS and 1H NMR) were combined to classify Amarone wines based on grape withering time and yeast strain. The study employed a multi-omics data integration approach, combining unsupervised data exploration (MCIA) and supervised statistical analysis (sPLS-DA). The results revealed that the multi-omics pseudo-eigenvalue space highlighted a limited correlation between the datasets (RV-score = 16.4%), suggesting the complementarity of the assays. Furthermore, the sPLS-DA models correctly classified wine samples according to both withering time and yeast strains, providing a much broader characterization of wine metabolome with respect to what was obtained from the individual techniques. Significant variations were notably observed in the accumulation of amino acids, monosaccharides, and polyphenolic compounds throughout the withering process, with a lower error rate in sample classification (7.52%). In conclusion, this strategy demonstrated a high capability to integrate large omics datasets and identify key metabolites able to discriminate wine samples based on their characteristics.PMID:39071933 | PMC:PMC11279979 | DOI:10.1016/j.fochx.2024.101607

Food Chem X. 2024 Jun 26;23:101600. doi: 10.1016/j.fochx.2024.101600. eCollection 2024 Oct 30.ABSTRACTSignificant differences exist in aroma and taste of different grades of large-leaf black tea. In this study, sensory histology combined with metabolomics were used to investigate the sensory characteristics and phytochemical profiles of different grades of Huangpu black tea (HPBT). Sensory evaluation showed that high grade HPBT had high intensity of pekoe, fresh aroma and umami, with aroma and taste scores declining with decreasing grades. 173 non-volatiles were identified, of which 23 marker metabolites could be used as discrimination of different grades HPBT taste. In addition, 154 volatile compounds were identified in the different grades of HPBT, with 15 compounds as key odorants for distinguishing the aroma of different grades of HPBT. Furthermore, correlation analysis revealed that linalool, geraniol and nonanal contributed to the aroma quality score of HPBT. This study will provide a more comprehensive understanding for processing, quality evaluation and grade evaluation system of large-leaf black tea.PMID:39071923 | PMC:PMC11283085 | DOI:10.1016/j.fochx.2024.101600

ISME Commun. 2024 Jul 20;4(1):ycae096. doi: 10.1093/ismeco/ycae096. eCollection 2024 Jan.ABSTRACTElectrogenic biofilms, which have attracted considerable attention in simultaneous wastewater treatment and energy recovery in bioelectrochemical systems, are regulated by chemical communication and potassium channel-mediated electrical signaling. However, how these two communication pathways interact with each other has not been thoroughly investigated. This study first explored the roles of chemical communication, including intracellular bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) and extracellular N-acyl-homoserine lactone (AHL)-mediated quorum sensing, in electrogenic biofilm formation through an integrated analysis of transcriptomics and metabolomics. Electrical signaling disruption inhibited the formation and electroactivity of Geobacter sulfurreducens biofilm, which was mainly ascribed to the reduction in biofilm viability and extracellular protein/polysaccharide ratio. The upregulation of expression levels of genes encoding c-di-GMP and AHL synthesis by transcriptomic analysis, and the increased secretion of N-butanoyl-L-homoserine lactone by metabolomic analysis confirmed the enhancement of chemical communication under electrical signaling disruption, thus indicating a compensatory mechanism among different signaling pathways. Furthermore, protein-protein interaction network showed the convergence of different signaling pathways, with c-di-GMP-related genes acting as central bridges. This study highlights the interaction of different signaling pathways, especially the resilience of c-di-GMP signaling to adverse external stresses, thereby laying the foundation for facilitating electrogenic biofilm formation under adverse conditions in practical applications.PMID:39071848 | PMC:PMC11283642 | DOI:10.1093/ismeco/ycae096

Drug Des Devel Ther. 2024 Jul 24;18:3209-3232. doi: 10.2147/DDDT.S462266. eCollection 2024.ABSTRACTBACKGROUND AND AIM: Previous studies of our research group have shown that Chuanxiong Renshen Decoction (CRD) has the effect of treating AD, but the exact mechanism of its effect is still not clarified. The aim of this study was to investigate the effect and mechanism of CRD on AD neuroinflammation.MATERIALS AND METHODS: Morris Water Maze (MWM) tests were employed to assess the memory and learning capacity of AD mice. HE and Nissl staining were used to observe the neural cells of mice. The expression of Iba-1 and CD86 were detected by immunohistochemical staining. Utilize UHPLC-MS/MS metabolomics techniques and the KEGG to analyze the metabolic pathways of CRD against AD. Lipopolysaccharide (LPS) induced BV2 microglia cells to construct a neuroinflammatory model. The expression of Iba-1 and CD86 were detected by immunofluorescence and flow cytometry. The contents of TNF-α and IL-1β were detected by ELISA. Western blot assay was used to detect the expression of PPARγ, p-NF-κB p65, NF-κB p65 proteins and inflammatory cytokines iNOS and COX-2 in PPARγ/NF-κB pathway with and without PPARγ inhibitor GW9662.RESULTS: CRD ameliorated the learning and memory ability of 3×Tg-AD mice, repaired the damaged nerve cells in the hippocampus, reduced the area of Iba-1 and CD86 positive areas in both the hippocampus and cortex regions, as well as attenuated serum levels of IL-1β and TNF-α in mice. CRD-containing serum significantly decreased the expression level of Iba-1, significantly reduced the levels of TNF-α and IL-1β, significantly increased the protein expression of PPARγ, and significantly decreased the proteins expression of iNOS, COX-2 and p-NF-κB p65 in BV2 microglia cells. After addition of PPARγ inhibitor GW9662, the inhibitory effect of CRD-containing serum on NF-κB activation was significantly weakened.CONCLUSION: CRD can activate PPARγ, regulating PPARγ/NF-κB signaling pathway, inhibiting microglia over-activation and reducing AD neuroinflammation.PMID:39071817 | PMC:PMC11283787 | DOI:10.2147/DDDT.S462266

Front Cell Dev Biol. 2024 Jul 12;12:1022181. doi: 10.3389/fcell.2024.1022181. eCollection 2024.ABSTRACTBACKGROUND: Pulmonary hypertension (PH) is a progressive disease affecting the lung vasculature that is characterized by sustained vasoconstriction and leads to vascular remodeling. The lung microbiome contributes to PH progression, but the function of the gut microbiome and the correlation between the gut microbiome and metabolome remain unclear. We have analyzed whether chronic hypoxia-induced PH alters the rat fecal microbiota.PURPOSE: We explored hypoxia-induced pulmonary hypertension model rats to find out the characteristic changes of intestinal microorganisms and metabolites of hypoxia-induced pulmonary hypertension, and provide a theoretical basis for clinical treatment.METHODS: In the current study, a chronic hypoxia-induced PH rat model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the occurrence and development of PH. 16S ribosomal ribonucleic acid (16S rRNA), short-chain fatty acid (SCFA) measurements, mass spectrometry (MS) metabolomics analysis and metatranscriptome were performed to analyze stool samples. The datasets were analyzed individually and integrated for combined analysis using bioinformatics approaches.RESULTS: Our results suggest that the gut microbiome and metabolome of chronic hypoxia-induced PH rats are distinct from those of normoxic rats and may thus aid in the search for new therapeutic or diagnostic paradigms for PH.CONCLUSION: The gut microbiome and metabolome are altered as a result of chronic hypoxia-induced PH. This imbalanced bacterial ecosystem might play a pathophysiological role in PH by altering homeostasis.PMID:39071798 | PMC:PMC11272533 | DOI:10.3389/fcell.2024.1022181

Heliyon. 2024 Jul 6;10(13):e34166. doi: 10.1016/j.heliyon.2024.e34166. eCollection 2024 Jul 15.ABSTRACTBACKGROUND: Cervical ripening is crucial for induction. However, its influencing factors, mechanistic understanding, and effective risk stratification are still challenging. Recent research suggested that microorganisms and their metabolites in vaginal spaces correlate to preterm birth. However, it remains unclear whether the cervicovaginal metabolome is related to the natural physiological process of cervical maturation.OBJECTIVE: We aimed to analyze the cervicovaginal metabolome in women with favorable induction cervix and those unfavorable for induction when delivering at term.STUDY DESIGN: Cervicovaginal swabs were collected between 40 and 41 weeks gestation from the following 2 different groups of patients: Ripe group (n = 25) which was favorable for the induction cervix and Unripe group which was unfavorable for the induction cervix (n = 25). Samples were tested using untargeted metabolomics analysis and analyzed by a bioinformatics platform. The correlation analysis between the metabolome and the previously acquired microbiome was also performed.RESULTS: A total of 629 metabolites were identified in cervicovaginal fluid. The cervicovaginal metabolome was significantly different between the women with the ripe cervix and those with the unripe cervix, especially within each stratum of the same CST. Metabolites within the amino acid, carbohydrate, and dipeptide pathways may play a role in this distinction. Thirty-four metabolites were significantly upregulated, and the remaining fourteen were significantly downregulated in the Unripe group with an unripe cervix unfavorable for induction. Statistical modeling identified Arachidonic Acid and Nicotinate associated with the risk of cervical maturation disorder (AUC 0.87) in negative ion mode. A combination of Choline and d-Mannose identified a risk of cervical maturation disorder (AUC 0.80) in positive ion mode, improved by Lactobacillus relative abundance (AUC 0.89).CONCLUSION: These data suggested that the cervicovaginal space was metabolically active during pregnancy and significantly altered among the women with the mature and immature cervix. Combining the genera-level phylotypes and metabolites could build better cervix maturity prediction models. By using cervicovaginal fluid samples, we demonstrated the potential of multi-data type integration for developing composite models toward understanding the contribution of the vaginal environment to the remodeling of cervix during term pregnancy.PMID:39071700 | PMC:PMC11279265 | DOI:10.1016/j.heliyon.2024.e34166

Heliyon. 2024 Jul 2;10(13):e34000. doi: 10.1016/j.heliyon.2024.e34000. eCollection 2024 Jul 15.ABSTRACTThe anti-cancer and anti-bacterial potential of the Red Sea sponge Phyllospongia lamellosa in its bulk (crude extracts) and gold nanostructure (loaded on gold nanaoparticles) were investigated. Metabolomics analysis was conducted, and subsequently, molecular modeling studies were conducted to explore and anticipate the P. lamellosa secondary metabolites and their potential target for their various bioactivities. The chloroformic extract (CE) and ethyl acetate extract (EE) of the P. lamellosa predicted to include bioactive lipophilic and moderately polar metabolites, respectively, were used to synthesize gold nanoparticles (AuNPs). The prepared AuNPs were characterized through transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV-vis spectrophotometric analyses. The cytotoxic activities were tested against MCF-7, MDB-231, and MCF-10A. Moreover, the anti-bacterial, antifungal, and anti-biofilm activity were assessed. Definite classes of metabolites were identified in CE (terpenoids) and EE (brominated phenyl ethers and sulfated fatty amides). Molecular modeling involving docking and molecular dynamics identified Protein-tyrosine phosphatase 1B (PTP1B) as a potential target for the anti-cancer activities of terpenoids. Moreover, CE exhibited the most powerful activity against breast cancer cell lines, matching our molecular modeling study. On the other hand, only EE was demonstrated to possess powerful anti-bacterial and anti-biofilm activity against Escherichia coli. In conclusion, depending on their bioactive metabolites, P. lamellosa-derived extracts, after being loaded on AuNPs, could be considered anti-cancer, anti-bacterial, and anti-biofilm bioactive products. Future work should be completed to produce drug leads.PMID:39071630 | PMC:PMC11283168 | DOI:10.1016/j.heliyon.2024.e34000

Heliyon. 2024 Jul 2;10(13):e33806. doi: 10.1016/j.heliyon.2024.e33806. eCollection 2024 Jul 15.ABSTRACTShaofuzhuyu Decoction (SFZYD) is a classical formula for treating endometriosis of cold coagulation and blood stasis (ECB). The clinical efficacy is definite, but the potential mechanisms require further exploration. The study aimed to reveal the metabolic mechanisms of SFZYD for treating ECB using mass spectrum oriented metabolomics. Firstly, the study has used metabolomics data to identify biomarkers and to investigate metabolic pathways. Then, the targets of SFZYD for treating ECB were dug by building and analyzing a biological network of biomarkers. Finally, the obtained targets were validated by molecular docking. This study found that SFZYD could significantly improve the biochemical indicators and metabolic abnormalities of ECB. A total of 18 ECB-related biomarkers in 7 pathways were identified. SFZYD was able to regulate the levels of 14 biomarkers that were involved in 5 metabolic pathways. Furthermore, the study yielded 119 SFZYD active ingredients, 1119 target proteins associated with endometriosis, 610 targets associated with biomarkers, 727 GO functions, and 159 KEGG pathways. Biological network analysis constructed a network diagram of herbs-ingredients-targets-biomarkers, and found 6 key active ingredients and 9 core targets. Molecular docking showed high affinities between key ingredients and core targets. This study elucidated that SFZYD plays a role in treating ECB through multi-component, multi-target, and multi-pathway.PMID:39071582 | PMC:PMC11279264 | DOI:10.1016/j.heliyon.2024.e33806

Heliyon. 2024 Jul 3;10(13):e33993. doi: 10.1016/j.heliyon.2024.e33993. eCollection 2024 Jul 15.ABSTRACTBACKGROUND: Quetiapine (QET) abuse has increased due to its anxiolytic and hedonic effects, necessitating protective adjunct treatments. Acacia saligna (A. saligna) flowers, used in traditional medicine, have potential health benefits.AIM: To investigate the protective role of A. saligna flower extract against QET-induced sexual toxicity, and to elucidate the possible underlying mechanisms through metabolomic and physiological studies.METHODS: A. saligna extract was subjected to metabolite profiling via High-Resolution Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-ESI-qTOF-MS). Forty-eight adult male albino rats were assigned into six groups for 30 days. The intracavernosal pressure (ICP), semen, biochemical, hormonal, histological, genetic and Western blot (WB) analyses were determined.RESULTS: A. saligna extract is rich in phenolic compounds, flavonoids, tannins, and unsaturated fatty acids. QET significantly decreased ICP and negatively affected semen parameters. A. saligna mitigated decreased sperm motility and ameliorated overexpressed proinflammatory genes in QET-55 group. A. saligna ameliorated the reduction of the antioxidant biomarkers, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), concurrent with downregulation of the nuclear factor kappa B (NF-κB) protein. A. saligna counteracted the disrupted testicular and prostatic structures revealed by histological examination.CONCLUSION: The extract from A. saligna, which contains a high concentration of antioxidants and anti-inflammatory chemicals, effectively mitigates sexual toxicity caused by QET. This study provided the first known explanation of the hypothesized processes behind the protective properties of A. saligna through biological, biochemical, and histological parameters. The results emphasize the potential of A. saligna as a safeguarding agent against drug-induced sexual toxicity.PMID:39071580 | PMC:PMC11280294 | DOI:10.1016/j.heliyon.2024.e33993