Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Exploring salivary metabolome alterations in people with HIV: towards early diagnostic markers

Mon, 24/06/2024 - 12:00
Front Public Health. 2024 Jun 5;12:1400332. doi: 10.3389/fpubh.2024.1400332. eCollection 2024.ABSTRACTBACKGROUND: The human immunodeficiency virus (HIV) remains a critical global health issue, with a pressing need for effective diagnostic and monitoring tools.METHODOLOGY: This study explored distinctions in salivary metabolome among healthy individuals, individuals with HIV, and those receiving highly active antiretroviral therapy (HAART). Utilizing LC-MS/MS for exhaustive metabolomics profiling, we analyzed 90 oral saliva samples from individuals with HIV, categorized by CD4 count levels in the peripheral blood.RESULTS: Orthogonal partial least squares-discriminant analysis (OPLS-DA) and other analyses underscored significant metabolic alterations in individuals with HIV, especially in energy metabolism pathways. Notably, post-HAART metabolic profiles indicated a substantial presence of exogenous metabolites and changes in amino acid pathways like arginine, proline, and lysine degradation. Key metabolites such as citric acid, L-glutamic acid, and L-histidine were identified as potential indicators of disease progression or recovery. Differential metabolite selection and functional enrichment analysis, combined with receiver operating characteristic (ROC) and random forest analyses, pinpointed potential biomarkers for different stages of HIV infection. Additionally, our research examined the interplay between oral metabolites and microorganisms such as herpes simplex virus type 1 (HSV1), bacteria, and fungi in individuals with HIV, revealing crucial interactions.CONCLUSION: This investigation seeks to contribute understanding into the metabolic shifts occurring in HIV infection and following the initiation of HAART, while tentatively proposing novel avenues for diagnostic and treatment monitoring through salivary metabolomics.PMID:38912274 | PMC:PMC11192068 | DOI:10.3389/fpubh.2024.1400332

Characteristics of the gut microbiota and serum metabolites in postmenopausal women with reduced bone mineral density

Mon, 24/06/2024 - 12:00
Front Cell Infect Microbiol. 2024 Jun 7;14:1367325. doi: 10.3389/fcimb.2024.1367325. eCollection 2024.ABSTRACTINTRODUCTION: Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women.METHODS: In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis.RESULTS: The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene.DISCUSSION: Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.PMID:38912210 | PMC:PMC11190063 | DOI:10.3389/fcimb.2024.1367325

Utilization of the Shensheng-Piwen changed medicinal powder extracts combines metal-organic frameworks as an antibacterial agent

Mon, 24/06/2024 - 12:00
Front Cell Infect Microbiol. 2024 Jun 7;14:1376312. doi: 10.3389/fcimb.2024.1376312. eCollection 2024.ABSTRACTINTRODUCTION: Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic resistance highlights the urgent need for novel antibacterial agents and alternative treatment approaches. Traditional Chinese Medicine (TCM) and its compounds have deep roots in the treatment of infectious diseases. It has a variety of active ingredients and multi-target properties, opening up new avenues for the discovery and development of antimicrobial drugs.METHODS: This study focuses on assessing the efficacy of the Shensheng-Piwen changed medicinal powder (SPC) extracts against opportunistic pathogen infections by broth microdilution and agar disc diffusion methods. Additionally, biofilm inhibition and eradication assays were performed to evaluate the antibiofilm effects of SPC extracts.RESULTS: Metabolite profiles were analyzed by LC-MS. Furthermore, the potential synergistic effect between SPC and Metal-Organic Framework (MOF) was investigated by bacterial growth curve analysis. The results indicated that the SPC extracts exhibited antibacterial activity against S. aureus, with a minimum inhibitory concentration (MIC) of 7.8 mg/mL (crude drug concentration). Notably, at 1/2 MIC, the SPC extracts significantly inhibited biofilm formation, with over 80% inhibition, which was critical in tackling chronic and hospital-acquired infections. Metabolomic analysis of S. aureus revealed that SPC extracts induced a notable reduction in the levels of various metabolites, including L-proline, L-asparagine. This suggested that the SPC extracts could interfere with the metabolism of S. aureus. Meanwhile, the growth curve experiment proved that SPC extracts and MOFs had a synergistic antibacterial effect.DISCUSSION: In conclusion, the present study highlights the potential of SPC extracts as a novel antibacterial agent against S. aureus infections, with promising biofilm inhibition properties. The observed synergistic effect between SPC extracts and MOFs further supports the exploration of this combination as an alternative treatment approach.PMID:38912207 | PMC:PMC11193333 | DOI:10.3389/fcimb.2024.1376312

Anti-chlamydial activity of vaginal fluids: new evidence from an <em>in vitro</em> model

Mon, 24/06/2024 - 12:00
Front Cell Infect Microbiol. 2024 Jun 7;14:1403782. doi: 10.3389/fcimb.2024.1403782. eCollection 2024.ABSTRACTINTRODUCTION: We assessed the in vitro anti-chlamydial activity of fresh vaginal secretions, deciphering the microbial and metabolic components able to counteract Chlamydia trachomatis viability.METHODS: Forty vaginal samples were collected from a group of reproductive-aged women and their anti-chlamydial activity was evaluated by inhibition experiments. Each sample underwent 16S rRNA metabarcoding sequencing to determine the bacterial composition, as well as 1H-NMR spectroscopy to detect and quantify the presence of vaginal metabolites.RESULTS: Samples characterized by a high anti-chlamydial activity were enriched in Lactobacillus, especially Lactobacillus crispatus and Lactobacillus iners, while not-active samples exhibited a significant reduction of lactobacilli, along with higher relative abundances of Streptococcus and Olegusella. Lactobacillus gasseri showed an opposite behavior compared to L. crispatus, being more prevalent in not-active vaginal samples. Higher concentrations of several amino acids (i.e., isoleucine, leucine, and aspartate; positively correlated to the abundance of L. crispatus and L. jensenii) lactate, and 4-aminobutyrate were the most significant metabolic fingerprints of highly active samples. Acetate and formate concentrations, on the other hand, were related to the abundances of a group of anaerobic opportunistic bacteria (including Prevotella, Dialister, Olegusella, Peptostreptococcus, Peptoniphilus, Finegoldia and Anaerococcus). Finally, glucose, correlated to Streptococcus, Lachnospira and Alloscardovia genera, emerged as a key molecule of the vaginal environment: indeed, the anti-chlamydial effect of vaginal fluids decreased as glucose concentrations increased.DISCUSSION: These findings could pave the way for novel strategies in the prevention and treatment of chlamydial urogenital infections, such as lactobacilli probiotic formulations or lactobacilli-derived postbiotics.PMID:38912205 | PMC:PMC11193362 | DOI:10.3389/fcimb.2024.1403782

Metabolomics and physio-chemical analyses of mulberry plants leaves response to manganese deficiency and toxicity reveal key metabolites and their pathways in manganese tolerance

Mon, 24/06/2024 - 12:00
Front Plant Sci. 2024 Jun 5;15:1349456. doi: 10.3389/fpls.2024.1349456. eCollection 2024.ABSTRACTINTRODUCTION: Manganese (Mn) plays a pivotal role in plant growth and development. Aside aiding in plant growth and development, Mn as heavy metal (HM) can be toxic in soil when applied in excess. Morus alba is an economically significant plant, capable of adapting to a range of environmental conditions and possessing the potential for phytoremediation of contaminated soil by HMs. The mechanism by which M. alba tolerates Mn stresses remains obscure.METHODS: In this study, Mn concentrations comprising sufficiency (0.15 mM), higher regimes (1.5 mM and 3 mM), and deficiency (0 mM and 0.03 mM), were applied to M. alba in pot treatment for 21 days to understand M. alba Mn tolerance. Mn stress effects on the net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), intercellular CO2 concentration (Ci), chlorophyll content, plant morphological traits, enzymatic and non-enzymatic parameters were analyzed as well as metabolome signatures via non-targeted LC-MS technique.RESULTS: Mn deficiency and toxicity decrease plant biomass, Pn, Ci, Gs, Tr, and chlorophyll content. Mn stresses induced a decline in the activities of catalase (CAT) and superoxide dismutase (SOD), while peroxidase (POD) activity, and leaf Mn content, increased. Soluble sugars, soluble proteins, malondialdehyde (MDA) and proline exhibited an elevation in Mn deficiency and toxicity concentrations. Metabolomic analysis indicates that Mn concentrations induced 1031 differentially expressed metabolites (DEMs), particularly amino acids, lipids, carbohydrates, benzene and derivatives and secondary metabolites. The DEMs are significantly enriched in alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, galactose metabolism, pantothenate and CoA biosynthesis, pentose phosphate pathway, carbon metabolism, etc.DISCUSSION AND CONCLUSION: The upregulation of Galactinol, Myo-inositol, Jasmonic acid, L-aspartic acid, Coproporphyrin I, Trigonelline, Pantothenol, and Pantothenate and their significance in the metabolic pathways makes them Mn stress tolerance metabolites in M. alba. Our findings reveal the fundamental understanding of DEMs in M. alba's response to Mn nutrition and the metabolic mechanisms involved, which may hold potential significance for the advancement of M. alba genetic improvement initiatives and phytoremediation programs.PMID:38911982 | PMC:PMC11192020 | DOI:10.3389/fpls.2024.1349456

Determination of the variations in the metabolic profiles and bacterial communities during traditional craftsmanship Liupao tea processing

Mon, 24/06/2024 - 12:00
Food Chem X. 2024 May 29;22:101516. doi: 10.1016/j.fochx.2024.101516. eCollection 2024 Jun 30.ABSTRACTIn this study, the metabolic profiles of traditional craftsmanship (TC) Liupao tea presented great changes at different processing stages. The contents of flavonoids and their glycosides generally exhibited a continuing downward trend, resulting in the sensory quality of TC-Liupao tea gradually improved. However, the taste of TC-Liupao tea faded when piling exceeded 12 h, as a result of the excessive degradation of some key flavor substances. Therefore, it could be deduced that piling for 10 h might be optimum for the quality formation of TC-Liupao tea. Sphingomonas, Acrobacter, Microbacterium, and Methylobacterium were the dominant bacteria during piling. The correlation analysis between differential metabolites and bacteria showed that only Sphingomonas and Massilia were significantly correlated to metabolites, demonstrating that the bacteria had less effect on the transformation of metabolites. Thus, the metabolic structure change during the process of TC-Liupao tea might be mainly attributed to the high temperature and humidity environment.PMID:38911914 | PMC:PMC11190490 | DOI:10.1016/j.fochx.2024.101516

Cohort profile: Improved Pregnancy Outcomes via Early Detection (IMPROvED), an International Multicentre Prospective Cohort

Mon, 24/06/2024 - 12:00
HRB Open Res. 2024 Feb 12;6:65. doi: 10.12688/hrbopenres.13812.2. eCollection 2023.ABSTRACTBACKGROUND: Improved Pregnancy Outcomes via Early Detection (IMPROvED) is a multi-centre, European phase IIa clinical study. The primary aim of IMPROvED is to enable the assessment and refinement of innovative prototype preeclampsia risk assessment tests based on emerging biomarker technologies. Here we describe IMPROvED's profile and invite researchers to collaborate.METHODS: A total of 4,038 low-risk nulliparous singleton pregnancies were recruited from maternity units in Ireland (N=1,501), United Kingdom (N=1,108), The Netherlands (N=810), and Sweden (N=619) between November 2013 to August 2017. Participants were interviewed by a research midwife at ~11 weeks (optional visit), ~15 weeks, ~20 weeks, ~34 weeks' gestation (optional visit), and postpartum (within 72-hours following delivery).FINDINGS TO DATE: Clinical data included information on maternal sociodemographic, medical history, and lifestyle factors collected at ~15 weeks' gestation, and maternal measurements, collected at each study visit. Biobank samples included blood, urine, and hair collected at each study visit throughout pregnancy in all units plus umbilical cord/blood samples collected at birth in Ireland and Sweden. A total of 74.0% (N=2,922) had an uncomplicated pregnancy, 3.1% (N=122) developed preeclampsia, 3.6% (N=143) had a spontaneous preterm birth, and 10.5% (N=416) had a small for gestational age baby. We evaluated a panel of metabolite biomarkers and a panel of protein biomarkers at 15 weeks and 20 weeks' gestation for preeclampsia risk assessment. Their translation into tests with clinical application, as conducted by commercial entities, was hampered by technical issues and changes in test requirements. Work on the panel of proteins was abandoned, while work on the use of metabolite biomarkers for preeclampsia risk assessment is ongoing.FUTURE PLANS: In accordance with the original goals of the IMPROvED study, the data and biobank are now available for international collaboration to conduct high quality research into the cause and prevention of adverse pregnancy outcomes.PMID:38911611 | PMC:PMC11190647 | DOI:10.12688/hrbopenres.13812.2

Consuming royal jelly alters several phenotypes associated with overwintering dormancy in mosquitoes

Mon, 24/06/2024 - 12:00
Front Insect Sci. 2024 Jun 7;4:1358619. doi: 10.3389/finsc.2024.1358619. eCollection 2024.ABSTRACTINTRODUCTION: Females of the Northern house mosquito, Culex pipiens, enter an overwintering dormancy, or diapause, in response to short day lengths and low environmental temperatures that is characterized by small egg follicles and high starvation resistance. During diapause, Culex pipiens Major Royal Jelly Protein 1 ortholog (CpMRJP1) is upregulated in females of Cx. pipiens. This protein is highly abundant in royal jelly, a substance produced by honey bees (Apis mellifera), that is fed to future queens throughout larval development and induces the queen phenotype (e.g., high reproductive activity and longer lifespan). However, the role of CpMRJP1 in Cx. pipiens is unknown.METHODS: We first conducted a phylogenetic analysis to determine how the sequence of CpMRJP1 compares with other species. We then investigated how supplementing the diets of both diapausing and nondiapausing females of Cx. pipiens with royal jelly affects egg follicle length, fat content, protein content, starvation resistance, and metabolic profile.RESULTS: We found that feeding royal jelly to females reared in long-day, diapause-averting conditions significantly reduced the egg follicle lengths and switched their metabolic profiles to be similar to diapausing females. In contrast, feeding royal jelly to females reared in short-day, diapause-inducing conditions significantly reduced lifespan and switched their metabolic profile to be similar nondiapausing mosquitoes. Moreover, RNAi directed against CpMRJPI significantly increased egg follicle length of short-day reared females, suggesting that these females averted diapause.DISCUSSION: Taken together, our data show that consuming royal jelly reverses several key seasonal phenotypes of Cx. pipiens and that these responses are likely mediated in part by CpMRJP1.PMID:38911605 | PMC:PMC11190361 | DOI:10.3389/finsc.2024.1358619

Exploring the effect of different tea varieties on the quality of Lu'an Guapian tea based on metabolomics and molecular sensory science

Mon, 24/06/2024 - 12:00
Food Chem X. 2024 Jun 4;23:101534. doi: 10.1016/j.fochx.2024.101534. eCollection 2024 Oct 30.ABSTRACTLu'an Guapian (LAGP) tea is one of the most famous teas in China. However, research on its suitable processing varieties is still lacking. This study analyzed the quality of LAGP tea made from three different tea varieties, namely, 'Anhui1' (AH1), 'Quntizhong' (QTZ), and 'Shuchazao' (SCZ), using molecular sensory science and metabolomics techniques. The results showed that AH1 had a strong floral aroma and the strongest umami flavor, while QTZ had a distinct roasted aroma and a mellow taste. SCZ had a cooked corn-like aroma and the highest bitterness and astringency owing to the high tea polyphenol contents and low free amino acid contents. The study also identified 12 key aroma-active compounds, with trans-beta-ionone and 2-ethyl-3,5-dimethyl-pyrazine contributing the most to floral and roasted aromas, respectively. The results of this study provide a theoretical and practical basis for selecting and breeding high-quality varieties of LAGP tea and stabilizing its quality.PMID:38911473 | PMC:PMC11192980 | DOI:10.1016/j.fochx.2024.101534

Branched-Chain Amino Acid Degradation Pathway was Inactivated in Colorectal Cancer: Results from a Proteomics Study

Mon, 24/06/2024 - 12:00
J Cancer. 2024 May 20;15(12):3724-3737. doi: 10.7150/jca.95454. eCollection 2024.ABSTRACTBackground: Colorectal cancer (CRC) ranks third in terms of cancer incidence and fourth in terms of cancer-related deaths worldwide. Identifying potential biomarkers of CRC is crucial for treatment and drug development. Methods: In this study, we established a C57B/6N mouse model of colon carcinogenesis using azoxymethane-dextran sodium sulfate (AOM-DSS) treatment for 14 weeks to identify proteins associated with colon cancer. An isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis was conducted on the cell membrane components enriched in the colonic mucosa. Additionally, tumor tissues and adjacent normal colon tissues were collected from patients with colon cancer for comparative protein and metabolite analyses. Results: In total, 74 differentially expressed proteins were identified in the tumor tissue samples from AOM/DSS-treated mice compared to both the adjacent tissue samples from AOM/DSS-treated mice and tissue samples from saline-treated control mice. Bioinformatics analysis revealed eight downregulated proteins enriched in the branched-chain amino acids pathway (valine, leucine, and isoleucine degradation). Moreover, these proteins are already known to be associated with the survival rate of patients with cancer. Targeted metabolomics showed increased levels of valine, leucine, and isoleucine in tumor tissues compared to those in adjacent normal tissues in patients with colon cancer. Furthermore, a real-time PCR experiment demonstrated that Aldehyde dehydrogenase, mitochondrial (short protein name ALDH2, gene name Aldh2) and Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (short protein name HCDH, gene name Hadh) (two genes) in the pathway of branched-chain amino acids) were downregulated in patients with colon cancer (colon tumor tissues vs. their adjacent colon tissues). ALDH2 expression was further validated by western blotting in AOM/DSS-treated mouse model and in clinical samples. Conclusion: This study highlighted the inactivation of the branched-chain amino acid degradation pathway in colon cancer and identified ALDH2 and HCDH as potential biomarkers for diagnosing colon cancer and developing new therapeutic strategies.PMID:38911385 | PMC:PMC11190764 | DOI:10.7150/jca.95454

Xanthohumol and echinocystic acid induces PSTVd tolerance in tomato

Mon, 24/06/2024 - 12:00
Plant Direct. 2024 Jun 20;8(6):e612. doi: 10.1002/pld3.612. eCollection 2024 Jun.ABSTRACTTomato is a popular vegetable worldwide; its production is highly threatened by infection with the potato spindle tuber viroid (PSTVd). We obtained the full-length genome sequence of previously conserved PSTVd and inoculated it on four genotypes of semi-cultivated tomatoes selected from a local tomato germplasm resource. SC-5, which is a PSTVd-resistant genotype, and SC-96, which is a PSTVd-sensitive genotype, were identified by detecting the fruit yield, plant growth, biomass accumulation, physiological indices, and PSTVd genome titer after PSTVd inoculation. A non-target metabolomics study was conducted on PSTVd-infected and control SC-5 to identify potential anti-PSTVd metabolites. The platform of liquid chromatography-mass spectrometry detected 158 or 123 differential regulated metabolites in modes of positive ion or negative ion. Principal component analysis revealed a clear separation of the global metabolite profile between PSTVd-infected leaves and control regardless of the detection mode. The potential anti-PSTVd compounds, xanthohumol, oxalicine B, indole-3-carbinol, and rosmarinic acid were significantly upregulated in positive ion mode, whereas echinocystic acid, chlorogenic acid, and 5-acetylsalicylic acid were upregulated in negative ion mode. Xanthohumol and echinocystic acid were detected as the most upregulated metabolites and were exogenously applied on PSTVd-diseased SC-96 seedlings. Both xanthohumol and echinocystic acid had instant and long-term inhibition effect on PSTVd titer. The highest reduction of disease symptom was induced by 2.6 mg/L of xanthohumol and 2.0 mg/L of echinocystic acid after 10 days of leaf spraying, respectively. A superior effect was seen on echinocystic acid than on xanthohumol. Our study provides a statistical basis for breeding anti-viroid tomato genotypes and creating plant-originating chemical preparations to prevent viroid disease.PMID:38911016 | PMC:PMC11190350 | DOI:10.1002/pld3.612

A Look into Ocular Diseases: The Pivotal Role of Omics Sciences in Ophthalmology Research

Mon, 24/06/2024 - 12:00
ACS Meas Sci Au. 2024 Feb 22;4(3):247-259. doi: 10.1021/acsmeasuresciau.3c00067. eCollection 2024 Jun 19.ABSTRACTPrecision medicine is a new medical approach which considers both population characteristics and individual variability to provide customized healthcare. The transition from traditional reactive medicine to personalized medicine is based on a biomarker-driven process and a deep knowledge of biological mechanisms according to which the development of diseases occurs. In this context, the advancements in high-throughput omics technologies represent a unique opportunity to discover novel biomarkers and to provide an unbiased picture of the biological system. One of the medical fields in which omics science has started to be recently applied is that of ophthalmology. Ocular diseases are very common, and some of them could be highly disabling, thus leading to vision loss and blindness. The pathogenic mechanism of most ocular diseases may be dependent on various genetic and environmental factors, whose effect has not been yet completely understood. In this context, large-scale omics approaches are fundamental to have a comprehensive evaluation of the whole system and represent an essential tool for the development of novel therapies. This Review summarizes the recent advancements in omics science applied to ophthalmology in the last ten years, in particular by focusing on proteomics, metabolomics and lipidomics applications from an analytical perspective. The role of high-efficiency separation techniques coupled to (high-resolution) mass spectrometry ((HR)MS) is also discussed, as well as the impact of sampling, sample preparation and data analysis as integrating parts of the analytical workflow.PMID:38910860 | PMC:PMC11191728 | DOI:10.1021/acsmeasuresciau.3c00067

A Study on the Protective Impact of Resveratrol on Liver Damage in Rats with Obstructive Jaundice

Mon, 24/06/2024 - 12:00
Comb Chem High Throughput Screen. 2024 Jun 21. doi: 10.2174/0113862073306667240606115002. Online ahead of print.ABSTRACTBACKGROUND: Obstructive Jaundice (OJ) is a common clinical condition with potential outcomes, including hepatocyte necrosis, bile duct hyperplasia, significant cholestatic liver fibrosis, and, in severe cases, liver failure. Resveratrol (RES), a polyphenol present in grapes and berries, has demonstrated efficacy in improving OJ. However, the precise mechanism of its action remains unclear.METHODS: In this study, we employed network pharmacology to investigate the underlying molecular mechanism of RES in the treatment of OJ. The targets of RES were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SuperPred, and SwissTargetPrediction database. The targets related to OJ were gathered from the DisGeNET, GeneCards, DrugBank, and Online Mendelian Inheritance in Man (OMIM) databases, and the intersection of these targets was determined using Venny2.1.0. Subsequently, an active component-target network was constructed using Cytoscape software. The Protein-Protein Interaction (PPI) network was generated using the String database and Cytoscape software. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Bioconductor platform. Finally, quantitative Real-Time PCR (qRT-PCR), Western Blotting (WB), and Enzyme-Linked Immunosorbent Assay (ELISA) were employed to assess RNA and protein expression levels in related pathways.RESULTS: The findings revealed a selection of 56 potential targets for RES, and a search through the online database identified 2,742 OJ-related targets with overlapping in 27 targets. In the PPI network, mTOR, CYP2C9, CYP1A1, CYP3A4, AHR, ESR1, and HSD17B1 emerged as core targets. KEGG analyses demonstrated that the primary pathways of RES in treating OJ, particularly those related to lipid metabolism, include linoleic acid metabolism, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450, lipid and atherosclerosis, tyrosine metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions signaling pathways. Furthermore, in vivo experiments indicated that RES significantly ameliorated liver injury induced by Common Bile Duct Ligation (CBDL) in rats with OJ. It lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue MDA levels, increased glutathione (GSH) content, and enhanced activity of superoxide dismutase (SOD), alleviating liver damage. Metabolomics analysis revealed that the therapeutic effect of RES in OJ involved alterations in lipid metabolic pathways, hinting at the potential mechanism of RES in treating OJ. ELISA, qRTPCR, and WB analyses confirmed lower expression levels of mTOR, CYP1A1, and CYP2C9 in the RES group compared to the model group, validating their involvement in the lipid metabolism pathway.CONCLUSION: In conclusion, RES exhibited a protective effect on liver function in rats with OJ. The underlying mechanism appears to be linked to antioxidant activity and modulation of lipid metabolism pathways.PMID:38910417 | DOI:10.2174/0113862073306667240606115002

Serum Metabolomics Reveals Metabolomic Profile and Potential Biomarkers in Asthma

Mon, 24/06/2024 - 12:00
Allergy Asthma Immunol Res. 2024 May;16(3):235-252. doi: 10.4168/aair.2024.16.3.235.ABSTRACTPURPOSE: Asthma is a highly heterogeneous disease. Metabolomics plays a pivotal role in the pathogenesis and development of asthma. The main aims of our study were to explore the underlying mechanism of asthma and to identify novel biomarkers through metabolomics approach.METHODS: Serum samples from 102 asthmatic patients and 18 healthy controls were collected and analyzed using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) system. Multivariate analysis and weighted gene co-expression network analysis (WGCNA) were performed to explore asthma-associated metabolomics profile and metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Subsequently, 2 selected serum hub metabolites, myristoleic acid and dodecanoylcarnitine, were replicated in a validation cohort using ultra-high performance LC-MS/MS system (UHPLC-MS/MS).RESULTS: Distinct metabolomics profile of asthma was revealed by multivariate analysis. Then, 116 overlapped asthma-associated metabolites between multivariate analysis and WGCNA, including 12 hub metabolites, were identified. Clinical features-associated hub metabolites were also identified by WGCNA. Among 116 asthma-associated metabolites, Sphingolipid metabolism and valine, leucine and isoleucine biosynthesis were revealed by KEGG analysis. Furthermore, serum myristoleic acid and dodecanoylcarnitine were significantly higher in asthmatic patients than in healthy controls in validation cohort. Additionally, serum myristoleic acid and dodecanoylcarnitine demonstrated high sensitivities and specificities in predicting asthma.CONCLUSIONS: Collectively, asthmatic patients showed a unique serum metabolome. Sphingolipid metabolism and valine, leucine and isoleucine biosynthesis were involved in the pathogenesis of asthma. Furthermore, our results suggest the promising values of serum myristoleic acid and dodecanoylcarnitine for asthma diagnosis in adults.PMID:38910282 | DOI:10.4168/aair.2024.16.3.235

Exploring Biomarkers in Asthma: Insights From Serum Metabolomics

Mon, 24/06/2024 - 12:00
Allergy Asthma Immunol Res. 2024 May;16(3):211-213. doi: 10.4168/aair.2024.16.3.211.NO ABSTRACTPMID:38910279 | DOI:10.4168/aair.2024.16.3.211

Conjugated linoleic acid (CLA) modulates bovine peripheral blood mononuclear cells (PBMC) proteome in vitro

Sun, 23/06/2024 - 12:00
J Proteomics. 2024 Jun 21:105232. doi: 10.1016/j.jprot.2024.105232. Online ahead of print.ABSTRACTConjugated linoleic acid (CLA) is a group of natural isomers of the n-6 polyunsaturated fatty acid (PUFA) linoleic acid, exerting biological effects on cow physiology. This study assessed the impact of the mixture 50:50 (vol:vol) of CLA isomers (cis-9, trans-11 and trans-10, cis-12) on bovine peripheral blood mononuclear cells (PBMC) proteome, identifying 1608 quantifiable proteins. A supervised multivariate statistical analysis, sparse variant partial least squares - discriminant analysis (sPLS-DA) for paired data identified 407 discriminant proteins (DP), allowing the clustering between the CLA and controls. The ProteINSIDE workflow found that DP with higher abundance in the CLA group included proteins related to innate immune defenses (PLIN2, CD36, C3, C4, and AGP), with antiapoptotic (SERPINF2 and ITIH4) and antioxidant effects (HMOX1). These results demonstrated that CLA modulates the bovine PBMC proteome, supports the antiapoptotic and immunomodulatory effects observed in previous in vitro studies on bovine PBMC, and suggests a cytoprotective role against oxidative stress. SIGNIFICANCE: In this study, we report for the first time that the mixture 50:50 (vol:vol) of cis-9, trans-11, and trans-10, cis-12-CLA isomers modulates the bovine PBMC proteome. Our results support the immunomodulatory and antiapoptotic effects observed in bovine PBMC in vitro. In addition, the present study proposes a cytoprotective role of CLA mixture against oxidative stress. We suggest a molecular signature of CLA treatment based on combining a multivariate sparse discriminant analysis and a clustering method. This demonstrates the great value of sPLS-DA as an alternative option to identify discriminant proteins with relevant biological significance.PMID:38909954 | DOI:10.1016/j.jprot.2024.105232

Liver tissue lipids in metabolic dysfunction-associated steatotic liver disease with diabetes and obesity

Sun, 23/06/2024 - 12:00
Clin Res Hepatol Gastroenterol. 2024 Jun 21:102402. doi: 10.1016/j.clinre.2024.102402. Online ahead of print.ABSTRACTBACKGROUND: Diabetes and obesity are associated with altered lipid metabolism and hepatic steatosis. Studies suggest that increases in lipid accumulation in these patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are not uniform for all lipid components. This study evaluates this variation.METHODS: A comprehensive lipidomic analysis of different lipid groups, were performed on liver tissue and plasma samples obtained at the time of histology from a well-defined cohort of 72 MASLD participants. The lipid profiles of controls were compared to those of MASLD patients with obesity, diabetes, or a combination of both.RESULTS: MASLD patients without obesity or diabetes exhibited distinct changes in the lipid profile of their liver tissue. The presence of diabetes or obesity further modified these lipid profiles (e.g., ceramide 47:7;4O), with positive or negative correlation (p<0.05). A step-wise increase (long-chain fatty acids, triglycerides, and ceramides) or decrease (ultra-long fatty acids, diglycerides, and phospholipids) for lipid groups was observed compared to control among patients with MASLD without obesity or diabetes to MASLD patients with obesity as a single risk factor, and MASLD patients with obesity and diabetes. Changes in lipids observed in the plasma did not align with their corresponding liver tissue findings.CONCLUSION: The changes observed in the composition of lipids are not similar in patients with obesity and diabetes among those with MASLD. This highlights the different metabolic processes at play. The presence of obesity or diabetes in patients with MASLD exacerbates these lipid derangements, underscoring the potential for targeted intervention in MASLD patients.PMID:38909684 | DOI:10.1016/j.clinre.2024.102402

Metabolic regulation of preimplantation embryo development in vivo and in vitro: Molecular mechanisms and insights

Sun, 23/06/2024 - 12:00
Biochem Biophys Res Commun. 2024 Jun 12;726:150256. doi: 10.1016/j.bbrc.2024.150256. Online ahead of print.ABSTRACTUnderstanding of embryonic development has led to the clinical application of Assisted Reproductive technologies (ART), with the resulting birth of millions of children. Recent developments in metabolomics, proteomics, and transcriptomics have brought to light new insights into embryonic growth dynamics, with implications spanning reproductive medicine, stem cell research, and regenerative medicine. The review explores the key metabolic processes and molecular pathways active during preimplantation embryo development, including PI3K-Akt, mTOR, AMPK, Wnt/β-catenin, TGF-β, Notch and Jak-Stat signaling pathways. We focused on analyzing the differences occurring in vitro as opposed to in vivo development and we discussed significant physiological and clinical implications.PMID:38909536 | DOI:10.1016/j.bbrc.2024.150256

Dietary succinate reduces fat deposition through gut microbiota and lipid metabolism in broilers

Sun, 23/06/2024 - 12:00
Poult Sci. 2024 Jun 6;103(8):103954. doi: 10.1016/j.psj.2024.103954. Online ahead of print.ABSTRACTSuccinate has been shown to be a potentially beneficial nutritional supplement with a diverse range of physiological functions. However, it remains unknown whether succinate supplementation regulates lipid metabolism in chickens. The aim of this study was to explore how succinate affects fat deposition and the underlying mechanism involved in broilers and to determine the most appropriate level of succinate supplementation in the diet. A total of 640 one-day-old male yellow-feathered broilers were randomly divided into 4 groups with 8 replicates and 20 broilers per replicate. A basal diet was provided to the control group (CON). The experimental broilers were fed diets containing 0.2% (L), 0.4% (M), or 0.6% (H) succinate and the study was lasted for 21 d. The linear (l) and quadratic (q) effects of succinate addition were determined. The results indicated that supplementation with 0.4% succinate reduced ADFI, serum triglycerides (l, q; P < 0.05), glucose (q; P < 0.05), and increased high-density lipidprotein cholesterol (l, q; P < 0.05) concentrations in broilers. Moreover, 0.4% succinate affects lipid metabolism by decreasing the abdominal fat percentage and adipocyte surface area, the expression of genes that promote liposynthesis in the abdominal fat and liver, as well as increasing the expression of genes that promote lipolysis in the abdominal fat and liver. In addition, increased cecal propionic acid content (q, P < 0.05) was found in the M group compared to the CON group. The 16S rRNA sequence analysis showed that group M altered cecum microbial composition by increasing the abundance of genera such as Blautia and Sellimonas (P < 0.05). LC-MS metabolomic analysis revealed that the differential metabolites between the M and CON groups were enriched in amino acid-related pathways. In conclusion, the optimum level of succinate added to broiler diets in the present study was 0.4%. Succinate can potentially reduce fat accumulation in broilers by modulating the composition of the gut flora and amino acid metabolism related to lipid metabolism.PMID:38909508 | DOI:10.1016/j.psj.2024.103954

Impact of dietary protein and energy levels on fatty acid profile, gut microbiome and cecal metabolome in native growing chickens

Sun, 23/06/2024 - 12:00
Poult Sci. 2024 May 29;103(8):103917. doi: 10.1016/j.psj.2024.103917. Online ahead of print.ABSTRACTThe present study investigated the optimal concentration of dietary ME and CP for the fatty acid profile of meat, gut microbiome, and cecal metabolome in Danzhou chickens from 120 to 150 d of age. A total of seven hundred and twenty 120-d-old Danzhou female chickens, with a similar BW, were randomly allocated into 6 treatments with 6 replicates and each of 20 birds. The chickens were fed 2 levels of dietary ME (11.70 MJ/kg, 12.50 MJ/kg), and 3 levels of dietary CP (13%, 14%, and 15%). The results showed that dietary ME and CP levels didn't affect final BW, ADG, ADFI, and feed gain ratio (g: g) (P > 0.05). The serum concentrations of triglyceride, insulin, and glucose in the 12.50 MJ/kg group were the highest (P < 0.05). Dietary ME, CP levels, and their interactions affected (P < 0.05) the fatty acid content in the breast muscle, thigh muscle, and liver. The levels of C18:0, C20:0, C22:0, C22:1, C18:2, C18:3, C22:6, and SFA of the liver in the high ME group were higher than those in the low ME group (P < 0.05). The levels of C16:0, C14:1, C18:1, C22:5, SFA, MUFA and USFA in the low CP group were higher than the corresponding values in the other groups (P < 0.05). Dietary ME and CP levels altered the composition and relative abundance of microbiota in the cecum of chickens at various taxonomic levels to different extents. Significant effects of interactions were found between dietary ME and CP on the relative abundance of 10 species (P < 0.05), and among these species, 6 species belonged to the genus Bacteroides. Notably, the relative abundance of 2 probiotic species including Lactobacillus crispatus and Lactobacillus salivarius was significantly increased (P < 0.05) with increasing dietary ME level. There were 6 differential metabolites in the cecum, comprising thromboxane A2, 5,6-DHET, prostaglandin D2, 20-hydroxyeicosatetraenoic acid, 12(S)-HPETE and prostaglandin I2 significantly reduced (P < 0.05) with increasing the dietary ME level; all of them are involved in arachidonic acid metabolism. In conclusion, the present study suggested that the dietary levels of 12.50 MJ/kg ME and 14% CP enhanced meat quality in terms of fatty acid composition, and showed benefits for maintaining intestinal health via positive regulation of cecal microbiota in native growing Danzhou chickens.PMID:38909505 | DOI:10.1016/j.psj.2024.103917

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