PubMed

iScience. 2024 Mar 1;27(4):109377. doi: 10.1016/j.isci.2024.109377. eCollection 2024 Apr 19.ABSTRACTGlycemic and body weight control gained from GLP-1R agonists remains an unmet need for diabetes and obesity treatment, leading to the development of GLP-1R/GIPR co-agonists. An imbalance in GLP-1R/GIPR agonism may extensively maximize the glucose- and weight-lowering effects. Hence, we prepared a potent and imbalanced GLP-1R/GIPR co-agonist, and refined its action time through a site-specific N-terminal PEGylation strategy. The pharmacological efficacy of these resulting long-acting co-agonists was interrogated both in vitro and in vivo. The results showed that peptide 1 possessed potent and imbalanced receptor-stimulating potency favoring GIP activity, but its hypoglycemic action was disrupted probably resulting from its short half-life. After PEGylation to improve the pharmacokinetics, the pharmacological effects were amplified compared to native peptide 1. Among the resulting derivatives, D-5K exhibited significant glycemic, HbA1c, body-weight, and food-intake control, outperforming GLP-1R mono-agonists. Based on its excellent pharmacological profiles, D-5K may hold the great therapeutic potential for diabetes and obesity treatment.PMID:38510128 | PMC:PMC10951637 | DOI:10.1016/j.isci.2024.109377

Adv Healthc Mater. 2024 Mar 20:e2304331. doi: 10.1002/adhm.202304331. Online ahead of print.ABSTRACTGlioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug-resistant progression. GBM "builds" around its primary core a genetically heterogeneous tumor-microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma-associated microglia (GAM) represent the largest population of collaborating cells, which, in the TME, usually exhibit the anti-inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth. Conversely, "classically activated" M1 microglia could provide pro-inflammatory and anti-tumorigenic activity, expected to exert a beneficial effect in defeating glioblastoma. In this work, we proposed an immunotherapy approach based on pro-inflammatory modulation of the GAM phenotype, through a controlled and localized electrical stimulation. The developed strategy relies on the wireless ultrasonic excitation of polymeric piezoelectric nanoparticles coated with GBM cell membrane extracts, to exploit homotypic targeting in anti-glioma applications. Such camouflaged nanotransducers locally generate electrical cues on GAM membranes, activating their M1 phenotype and ultimately triggering a promising anti-cancer activity. Collected findings open new perspectives in the modulation of immune cell activities through "smart" nanomaterials and, more specifically, provide an innovative auspicious tool in glioma immunotherapy. This article is protected by copyright. All rights reserved.PMID:38509761 | DOI:10.1002/adhm.202304331

BMC Plant Biol. 2024 Mar 20;24(1):203. doi: 10.1186/s12870-024-04821-2.ABSTRACTBACKGROUND: Quinoa leaves demonstrate a diverse array of colors, offering a potential enhancement to landscape aesthetics and the development of leisure-oriented sightseeing agriculture in semi-arid regions. This study utilized integrated transcriptomic and metabolomic analyses to investigate the mechanisms underlying anthocyanin synthesis in both emerald green and pink quinoa leaves.RESULTS: Integrated transcriptomic and metabolomic analyses indicated that both flavonoid biosynthesis pathway (ko00941) and anthocyanin biosynthesis pathway (ko00942) were significantly associated with anthocyanin biosynthesis. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were analyzed between the two germplasms during different developmental periods. Ten DEGs were verified using qRT-PCR, and the results were consistent with those of the transcriptomic sequencing. The elevated expression of phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), 4-coumarate CoA ligase (4CL) and Hydroxycinnamoyltransferase (HCT), as well as the reduced expression of flavanone 3-hydroxylase (F3H) and Flavonol synthase (FLS), likely cause pink leaf formation. In addition, bHLH14, WRKY46, and TGA indirectly affected the activities of CHS and 4CL, collectively regulating the levels of cyanidin 3-O-(3'', 6''-O-dimalonyl) glucoside and naringenin. The diminished expression of PAL, 4CL, and HCT decreased the formation of cyanidin-3-O-(6"-O-malonyl-2"-O-glucuronyl) glucoside, leading to the emergence of emerald green leaves. Moreover, the lowered expression of TGA and WRKY46 indirectly regulated 4CL activity, serving as another important factor in maintaining the emerald green hue in leaves N1, N2, and N3.CONCLUSION: These findings establish a foundation for elucidating the molecular regulatory mechanisms governing anthocyanin biosynthesis in quinoa leaves, and also provide some theoretical basis for the development of leisure and sightseeing agriculture.PMID:38509491 | DOI:10.1186/s12870-024-04821-2

Curr Top Behav Neurosci. 2024 Mar 21. doi: 10.1007/7854_2024_463. Online ahead of print.ABSTRACTMetabolomics technologies enable the quantification of multiple metabolomic measures simultaneously, which provides novel insights into molecular aspects of human health and disease. In large-scale, population-based studies, blood is often the preferred biospecimen. Circulating metabolome may relate to brain health either by affecting or reflecting brain metabolism. Peripheral metabolites may act at or cross the blood-brain barrier and, subsequently, influence brain metabolism, or they may reflect brain metabolism if similar pathways are engaged. Peripheral metabolites may also include those penetrating the circulation from the brain, indicating, for example, brain damage. Most brain health-related metabolomics studies have been conducted in the context of neurodegenerative disorders and cognition, but some studies have also focused on neuroimaging markers of these disorders. Moreover, several metabolomics studies of neurodevelopmental disorders have been performed. Here, we provide a brief background on the types of blood metabolites commonly assessed, and we review the literature describing the relationships between human blood metabolome (n > 50 metabolites) and brain health reported in large-scale studies (n > 500 individuals).PMID:38509405 | DOI:10.1007/7854_2024_463

Pediatr Res. 2024 Mar 20. doi: 10.1038/s41390-024-03129-z. Online ahead of print.ABSTRACTBACKGROUND: Gut-derived metabolites, products of microbial and host co-metabolism, may inform mechanisms underlying children's neurodevelopment. We investigated whether infant fecal metabolites were related to toddler social behavior.METHODS: Stool samples collected from 6-week-olds (n = 86) and 1-year-olds (n = 209) in the New Hampshire Birth Cohort Study (NHBCS) were analyzed using nuclear magnetic resonance spectroscopy metabolomics. Autism-related behavior in 3-year-olds was assessed by caregivers using the Social Responsiveness Scale (SRS-2). To assess the association between metabolites and SRS-2 scores, we used a traditional single-metabolite approach, quantitative metabolite set enrichment (QEA), and self-organizing maps (SOMs).RESULTS: Using a single-metabolite approach and QEA, no individual fecal metabolite or metabolite set at either age was associated with SRS-2 scores. Using the SOM method, fecal metabolites of six-week-olds organized into four profiles, which were unrelated to SRS-2 scores. In 1-year-olds, one of twelve fecal metabolite profiles was associated with fewer autism-related behaviors, with SRS-2 scores 3.4 (95%CI: -7, 0.2) points lower than the referent group. This profile had higher concentrations of lactate and lower concentrations of short chain fatty acids than the reference.CONCLUSIONS: We uncovered metabolic profiles in infant stool associated with subsequent social behavior, highlighting one potential mechanism by which gut bacteria may influence neurobehavior.IMPACT: Differences in host and microbial metabolism may explain variability in neurobehavioral phenotypes, but prior studies do not have consistent results. We applied three statistical techniques to explore fecal metabolite differences related to social behavior, including self-organizing maps (SOMs), a novel machine learning algorithm. A 1-year-old fecal metabolite pattern characterized by high lactate and low short-chain fatty acid concentrations, identified using SOMs, was associated with social behavior less indicative of autism spectrum disorder. Our findings suggest that social behavior may be related to metabolite profiles and that future studies may uncover novel findings by applying the SOM algorithm.PMID:38509226 | DOI:10.1038/s41390-024-03129-z

Sci Rep. 2024 Mar 20;14(1):6732. doi: 10.1038/s41598-024-57238-0.ABSTRACTEminent in pandemic management is accurate information on infection dynamics to plan for timely installation of control measures and vaccination campaigns. Despite huge efforts in diagnostic testing of individuals, the underestimation of the actual number of SARS-CoV-2 infections remains significant due to the large number of undocumented cases. In this paper we demonstrate and compare three methods to estimate the dynamics of true infections based on secondary data i.e., (a) test positivity, (b) infection fatality and (c) wastewater monitoring. The concept is tested with Austrian data on a national basis for the period of April 2020 to December 2022. Further, we use the results of prevalence studies from the same period to generate (upper and lower bounds of) credible intervals for true infections for four data points. Model parameters are subsequently estimated by applying Approximate Bayesian Computation-rejection sampling and Genetic Algorithms. The method is then validated for the case study Vienna. We find that all three methods yield fairly similar results for estimating the true number of infections, which supports the idea that all three datasets contain similar baseline information. None of them is considered superior, as their advantages and shortcomings depend on the specific case study at hand.PMID:38509181 | DOI:10.1038/s41598-024-57238-0

Sci Rep. 2024 Mar 20;14(1):6691. doi: 10.1038/s41598-024-57237-1.ABSTRACTThe clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.PMID:38509170 | DOI:10.1038/s41598-024-57237-1

NPJ Biofilms Microbiomes. 2024 Mar 20;10(1):26. doi: 10.1038/s41522-024-00500-0.ABSTRACTThere is a deficiency in population-based studies investigating the impact of HPV infection on vaginal microenvironment, which influences the risk of persistent HPV infection. This prospective study aimed to unravel the dynamics of vaginal microbiota (VM) and vaginal metabolome in reaction to the changed state of HPV infection. Our results propose that the vaginal metabolome may be a superior indicator to VM when assessing the impact of altered HPV state on the vaginal microenvironment.PMID:38509123 | DOI:10.1038/s41522-024-00500-0

Nutr Metab Cardiovasc Dis. 2024 Feb 7:S0939-4753(24)00056-5. doi: 10.1016/j.numecd.2024.02.001. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Hyperuricemia frequently accompanies dyslipidemia, yet the precise mechanism remains elusive. Leveraging cellular metabolomics analyses, this research probes the potential mechanisms wherein hyperuricemia provokes endothelial cell abnormalities, inducing disordered bile metabolism and resultant lipid anomalies.METHODS AND RESULTS: We aimed to identify the differential metabolite associated with lipid metabolism through adopting metabolomics approach, and thereafter adequately validating its protective function on HUVECs by using diverse assays to measure cellular viability, reactive oxygen species, migration potential, apoptosis and gene and protein levels of inflammatory factors. Taurochenodeoxycholic acid (TCDCA) (the differential metabolite of HUVECs) and the TCDCA-involved primary bile acid synthesis pathway were found to be negatively correlated with high UA levels based on the results of metabolomics analysis. It was noted that compared to the outcomes observed in UA-treated HUVECs, TCDCA could protect against UA-induced cellular damage and oxidative stress, increase proliferation as well as migration, and decreases apoptosis. In addition, it was observed that TCDCA might protect HUVECs by inhibiting UA-induced p38 mitogen-activated protein kinase/nuclear factor kappa-B p65 (p38MAPK/NF-κB p65) pathway gene and protein levels, as well as the levels of downstream inflammatory factors.CONCLUSION: The pathogenesis of hyperuricemia accompanying dyslipidemia may involve high uric acid levels eliciting inflammatory reactions and cellular damage in human umbilical vein endothelial cells (HUVECs), mediated through the p38MAPK/NF-κB signaling pathway, subsequently impinging on cellular bile acid synthesis and reducing bile acid production.PMID:38508990 | DOI:10.1016/j.numecd.2024.02.001

Trends Parasitol. 2024 Mar 19:S1471-4922(24)00032-1. doi: 10.1016/j.pt.2024.02.007. Online ahead of print.ABSTRACTDespite years of research, malaria remains a significant global health burden, with poor diagnostic tests and increasing antimalarial drug resistance challenging diagnosis and treatment. While 'single-omics'-based approaches have been instrumental in gaining insight into the biology and pathogenicity of the Plasmodium parasite and its interaction with the human host, a more comprehensive understanding of malaria pathogenesis can be achieved through 'multi-omics' approaches. Integrative methods, which combine metabolomics, lipidomics, transcriptomics, and genomics datasets, offer a holistic systems biology approach to studying malaria. This review highlights recent advances, future directions, and challenges involved in using integrative metabolomics approaches to interrogate the interactions between Plasmodium and the human host, paving the way towards targeted antimalaria therapeutics and control intervention methods.PMID:38508901 | DOI:10.1016/j.pt.2024.02.007

Clin Chim Acta. 2024 Mar 18:117860. doi: 10.1016/j.cca.2024.117860. Online ahead of print.ABSTRACTBACKGROUND: Polycystic ovary syndrome (PCOS) is a common infertility disorder which affects reproductive-aged women. However, metabolic change profiles of follicular fluid (FF) in lean and obese women diagnosed with and without PCOS remains unclear.METHODS: 95 infertile women were divided into four subgroups: LC (lean control), OC (overweight control), LP (lean PCOS), and OP (overweight PCOS). The FF samples were collected during oocyte retrieval and assayed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) metabolomics.RESULTS: A total of 236 metabolites were identified by metabolic analysis. The pathway enrichment analysis revealed that the glycerophospholipid metabolism (impact = 0.11182), ether lipid metabolism (impact = 0.14458), and primary bile acid biosynthesis (impact = 0.03267) were related to metabolic pathway between PCOS and control. Correlation analyses showed that epitestosterone sulfate was found positively correlated with fertilization rate in PCOS, while falcarindione, lucidone C. and notoginsenoside I was found to be negatively correlated. The combined four biomarkers including lucidone C, epitestosterone sulfate, falcarindione, and notoginsenoside I was better in predicting live birth rate, with AUC of 0.779.CONCLUSION: The follicular fluid of women with PCOS showed unique metabolic characteristics. Our study provides better identification of PCOS follicular fluid metabolic dynamics, which may serve as potential biomarkers of live birth.PMID:38508572 | DOI:10.1016/j.cca.2024.117860

Chemosphere. 2024 Mar 18:141682. doi: 10.1016/j.chemosphere.2024.141682. Online ahead of print.ABSTRACTParabens (PBs), a group of widely used synthetic preservatives with potential endocrine-disrupting activity, have been detected with increasing frequency in organisms and environmental matrices. This study assessed the endocrine hormone interference effects of four typical PBs, namely methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), in zebrafish and elucidated the probable underlying mechanisms. Transcriptomic and metabolomic analyses showed that the differentially expressed genes and metabolites were associated with the tyrosine metabolism, arachidonate metabolism, and glycerophospholipid metabolism, indicating they were essential precursors of steroid hormone biosynthesis and metabolism. Histopathological analysis revealed impaired gonad development in the zebrafish exposed to PBs, in accordance with the significantly increased vitellogenin (VTG) and estradiol (E2) levels. Furthermore, molecular dynamics simulation suggested that the four PBs could preferentially to activate zebrafish estrogen receptor (zfERβ2) to regulate the downstream pathways. Disruption of the amino acid metabolism and lipid metabolism, and activation of zfERβ2 signaling pathway were found to be the key mechanisms for the endocrine-disrupting effect of PBs. The endocrine disrupting effects of PBs were found to be dependent on the shared oxybenzene on their structures, with the degree of interference determined largely by the elongation of their alkyl groups. These findings provide new insights into the endocrine disrupting effects of PBs and could help better assess their risk to human health.PMID:38508462 | DOI:10.1016/j.chemosphere.2024.141682

J Ethnopharmacol. 2024 Mar 18:118065. doi: 10.1016/j.jep.2024.118065. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Cornel iridoid glycosides (CIG) are extracted from Corni fructus, a herbal medicine used in traditional Chinese medicine to treat diabetes. However, the antidiabetic effects of CIG and the underlying metabolic mechanisms require further exploration.AIM OF THE STUDY: This study aimed to assess the antidiabetic effects and metabolic mechanism of CIG by performing metabolomic analyses of serum and urine samples of rats.MATERIALS AND METHODS: A rat model of type 2 diabetes mellitus (T2DM) was established by administering a low dose of streptozotocin (30 mg/kg) intraperitoneally after 4 weeks of feeding a high-fat diet. The model was evaluated based on several parameters, including fasting blood glucose (FBG), random blood glucose (RBG), urine volume, liver index, body weight, histopathological sections, and serum biochemical parameters. Subsequently, serum and urine metabolomics were analyzed using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS). Data were analyzed using unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares discriminant analysis (OPLS-DA). Differential metabolites were examined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways to explore the underlying mechanisms.RESULTS: After 4 weeks of treatment with different doses of CIG, varying degrees of antidiabetic effects were observed, along with reduced liver and pancreatic injury, and improved oxidative stress levels. Compared with the T2DM group, 19 and 23 differential metabolites were detected in the serum and urine of the CIG treatment group, respectively. The key metabolites involved in pathway regulation include taurine, chenodeoxycholic acid, glycocholic acid, and L-tyrosine in the serum and glycine, hippuric acid, phenylacetylglycine, citric acid, and D-glucuronic acid in the urine, which are related to lipid, amino acid, energy, and carbohydrate metabolism.CONCLUSIONS: This study confirmed the antidiabetic effects of CIG and revealed that CIG effectively controlled metabolic disorders in T2DM rats. This seems to be meaningful for the clinical application of CIG, and can benefit further studies on CIG mechanism.PMID:38508432 | DOI:10.1016/j.jep.2024.118065

Comp Biochem Physiol C Toxicol Pharmacol. 2024 Mar 18:109904. doi: 10.1016/j.cbpc.2024.109904. Online ahead of print.ABSTRACTMicrocystins (MCs) are prevalent harmful contaminants within shrimp aquaculture systems, exhibiting a diverse array of variants. Gut microbiota can engage in mutual interactions with the host through the gut-liver axis. In this study, the shrimp Litopenaeus vannamei were subjected to three different variants of MCs (LR, YR, RR) at a concentration of 1 μg/L each, and elucidated the alterations in both intestinal microbiota and hepatopancreas physiological homeostasis. The results indicate that all three variants of MCs prompted histological alterations in the hepatopancreas, induced elevated levels of oxidative stress biomarkers (H2O2, SOD, and CAT), disturbed the transcription levels of immune-related genes (Crus, ALF, and Lys), along with an increase in apoptotic genes (Casp-3 and P53). Furthermore, the metabolic profiles of the hepatopancreas were perturbed, particularly in amino acid metabolism such as "lysine degradation" and "β-alanine metabolism"; the mTOR and FoxO signaling were also influenced, encompassing alterations in the transcription levels of related genes. Additionally, the alterations were observed in the intestinal microbiota's diversity and composition, particularly potential beneficial bacteria (Alloprevotella, Bacteroides, Collinsella, Faecalibacterium, and Prevotellaceae UCG-001), which exhibited a positive correlation with the metabolite berberine. These findings reveal that the three MCs variants can impact the health of the shrimp by interfering with the homeostasis of intestinal microbial and hepatopancreas physiology.PMID:38508355 | DOI:10.1016/j.cbpc.2024.109904

J Hepatol. 2024 Mar 18:S0168-8278(24)00199-5. doi: 10.1016/j.jhep.2024.03.016. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with high lethality. Clonorchis sinensis (C. sinensis) infection is an important risk factor for ICC. Here we investigated the clinical impact and underlying molecular characteristics of C. sinensis-infected ICC.METHODS: We performed single-cell RNA sequencing, whole exome sequencing, RNA-sequencing, metabolomics and spatial transcriptomics in 251 ICC patients from three medical centers. The alterations of metabolic and immune microenvironment of C. sinensis-infected ICCs were validated through in vitro co-culture system and hydrodynamic injection ICC mouse model.RESULTS: We revealed that C. sinensis infection was significantly associated with ICC patients' overall survival and immunotherapy response. Fatty acid biosynthesis and the expression of FASN, a key enzyme catalyzing long-chain fatty acid synthesis, were significantly enriched in C. sinensis-infected ICCs. ICC cell lines treated with C. sinensis-produced excretory/secretory products (ESPs) displayed an elevation of FASN and free fatty acid. The metabolic alteration of tumor cells was closely correlated with the enrichment of tumor-associated macrophage-like (TAM-like) macrophages and the impairment function of T cells, which led to the immunosuppressive microenvironment formation and tumor progression. Spatial transcriptomics analysis revealed that malignant cells were in closer juxtaposition with TAM-like macrophages in C. sinensis-infected ICCs than non-C. sinensis-infected ICCs. Importantly, FASN inhibitor significantly reversed immunosuppressive microenvironment and enhanced anti-PD-1 efficacy in ICC mouse models treated with ESPs from C. sinensis.CONCLUSIONS: We uncover the metabolic signature and immune microenvironment of C. sinensis-infected ICCs and highlight the combination of FASN inhibitors with immunotherapy as a promising strategy for treating C. sinensis-infected ICCs.IMPACT AND IMPLICATIONS: C. sinensis-infected ICC patients have a poorer prognosis and worse response to immunotherapy than non-C. sinensis-infected ICCs. The underlying molecular characteristics of C. sinensis-infected ICCs remains unclear. Herein, we demonstrate that up-regulation of FASN and free fatty acids in C. sinensis-infected ICCs leads to immunosuppressive microenvironment formation and tumor progression. Thus, administration of FASN inhibitors could significantly reverse immunosuppressive environment and further enhance anti-PD-1 efficacy in combating C. sinensis-infected ICCs.PMID:38508240 | DOI:10.1016/j.jhep.2024.03.016

Food Chem. 2024 Mar 15;447:139005. doi: 10.1016/j.foodchem.2024.139005. Online ahead of print.ABSTRACTHydrogen sulfide (H2S) is known to effectively inhibit the browning of fresh-cut apples, but the mechanism at a metabolic level remains unclear. Herein, non-targeted metabolomics was used to analyze metabolic changes in surface and internal tissues of fresh-cut apple after H2S treatment. The results showed that prenol lipids were the most up-accumulated differential metabolites in both surface and inner tissue of fresh-cut apple during browning process, which significantly down-accumulated by H2S treatment. H2S treatment reduced the consumption of amino acid in surface tissue. Regarding inner tissue, H2S activated defense response through accumulation of lysophospholipid signaling and induced the biosynthesis of phenolic compounds. We therefore propose that H2S inhibited the surface browning of fresh-cut apple by reducing the accumulation of prenol lipids, directly delaying amino acid consumption in surface tissue and indirectly regulating defense response in inner tissue, which provides fundamental insights into browning inhibition mechanisms by H2S.PMID:38507948 | DOI:10.1016/j.foodchem.2024.139005

Food Chem. 2024 Mar 12;447:138969. doi: 10.1016/j.foodchem.2024.138969. Online ahead of print.ABSTRACTFood authenticity is extremely important and widely targeted bi-omics is a promising pipeline attributing to incorporating metabolomics and peptidomics. Colla Corii Asini (CCA, Ejiao) is one of the most popular tonic edible materials, with counterfeit and adulterated products being widespread. An attempt was devoted to develop a high-throughput and reliable DI-MRM3 program facilitating widely targeted bi-omics of CCA. Firstly, predictive MRM program captured metabolites and peptides in trypsin-digestive gelatins. After data alignment and structure annotation, primary parameters such as Q1 → Q3 → QLIT, CE, and EE were optimized for all 17 metabolites and 34 peptides by online ER-MS. Though a single run merely consumed 6.5 min, great selectivity was reached for each analyte. Statistical results showed that nine peptides contributed to distinguish CCA from other gelatins. After cross-validation with LC-MRM, DI-MRM3 was justified to be reproducible and high-throughput for widely targeted bi-omics of CCA, suggesting a meaningful tool for food authenticity.PMID:38507947 | DOI:10.1016/j.foodchem.2024.138969

J Proteome Res. 2024 Mar 20. doi: 10.1021/acs.jproteome.3c00685. Online ahead of print.ABSTRACTProteins usually execute their biological functions through interactions with other proteins and by forming macromolecular complexes, but global profiling of protein complexes directly from human tissue samples has been limited. In this study, we utilized cofractionation mass spectrometry (CF-MS) to map protein complexes within the postmortem human brain with experimental replicates. First, we used concatenated anion and cation Ion Exchange Chromatography (IEX) to separate native protein complexes in 192 fractions and then proceeded with Data-Independent Acquisition (DIA) mass spectrometry to analyze the proteins in each fraction, quantifying a total of 4,804 proteins with 3,260 overlapping in both replicates. We improved the DIA's quantitative accuracy by implementing a constant amount of bovine serum albumin (BSA) in each fraction as an internal standard. Next, advanced computational pipelines, which integrate both a database-based complex analysis and an unbiased protein-protein interaction (PPI) search, were applied to identify protein complexes and construct protein-protein interaction networks in the human brain. Our study led to the identification of 486 protein complexes and 10054 binary protein-protein interactions, which represents the first global profiling of human brain PPIs using CF-MS. Overall, this study offers a resource and tool for a wide range of human brain research, including the identification of disease-specific protein complexes in the future.PMID:38507900 | DOI:10.1021/acs.jproteome.3c00685

J Chromatogr A. 2024 Mar 15;1720:464820. doi: 10.1016/j.chroma.2024.464820. Online ahead of print.ABSTRACTHighly polar low molecular weight organic molecules are still very challenging to analyze by liquid chromatography. Yet, with the steadily increasing application of metabolomics and similar approaches in chemical analysis, separating polar compounds might be even more important. However, almost all established liquid chromatography techniques (i.e., normal and reversed phase, hydrophilic interaction liquid chromatography (HILIC), ion chromatography) struggle with either carry-over, low sensitivity, or a lack of retention. For improving these shortcomings, electrostatic repulsion hydrophilic interaction chromatography (ERLIC) might be an alternative. By combining a HILIC mobile phase, that is highly organic with a low water content, and an ion exchange column, a distinct layer system develops. When the analyte's charge is of the same direction as the stationary phase, retention and elution are determined by two antagonistic forces: electrostatic repulsion and hydrophilicity. One prominent group of challenging polar analytes are the polyamines cadaverine, putrescine, spermidine, and spermine. Carrying charges from +2 to +4 at physiological pH, these compounds are essential cell constituents and found in all living organisms. However, they are still notoriously challenging to analyze via the established liquid chromatography methods. In the present work, an ERLIC tandem mass spectrometry method has been exemplarily developed, optimized, and validated for the quantitative determination of cadaverine, putrescine, spermidine, and spermine. This method enables symmetrical peak shapes and good separation of analytes with different charges while simultaneously selectively detecting the co-eluting diamines by MS/MS. Furthermore, high linearity (R > 0.998) and sensitivity (LODs ≤ 2 ng/mL) have been proven. Thus, ERLIC may be interesting for both targeted and untargeted analysis approaches of highly charged low molecular weight organic molecules.PMID:38507872 | DOI:10.1016/j.chroma.2024.464820

Biochem Biophys Res Commun. 2024 Mar 16;708:149778. doi: 10.1016/j.bbrc.2024.149778. Online ahead of print.ABSTRACTThe increasing prevalence of lean diabetes has prompted the generation of animal models that mimic metabolic disease in humans. This study aimed to determine the optimum streptozotocin-nicotinamide (STZ-NA) dosage ratio to elicit lean diabetic features in a rat model. It also used a proton nuclear magnetic resonance (1H NMR) urinary metabolomics approach to identify the metabolic effect of metformin treatment on this novel rat model. Three different STZ-NA dosage regimens (by body weight: Group A: 110 mg/kg NA and 45 mg/kg STZ; Group B: 180 mg/kg NA and 65 mg/kg STZ and Group C: 120 mg/kg NA and 60 mg/kg STZ) were administered to Sprague-Dawley rats along with oral metformin. Group A diabetic rats (A-DC) showed favorable serum biochemical analyses and a more positive response toward oral metformin administration relative to the other STZ-NA dosage ratio groups. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that glucose, citrate, pyruvate, hippurate, and methylnicotinamide differentiating the OPLS-DA of A-MTF rats (Group A diabetic rats treated with metformin) and A-DC model rats. Subsequent metabolic pathway analyses revealed that metformin treatment was associated with improvement in dysfunctions caused by STZ-NA induction, including carbohydrate metabolism, cofactor metabolism, and vitamin and amino acid metabolism. In conclusion, our results identify the best STZ-NA dosage ratio for a rat model to exhibit lean type 2 diabetic features with optimum sensitivity to metformin treatment. The data presented here could be informative to improve our understanding of non-obese diabetes in humans through the identification of possible activated metabolic pathways in the STZ-NA-induced diabetic rats model.PMID:38507867 | DOI:10.1016/j.bbrc.2024.149778