PubMed

Int J Mol Sci. 2022 Nov 9;23(22):13767. doi: 10.3390/ijms232213767.ABSTRACTTo clarify the differences in the clinical application scope of Chrysanthemum morifolium flower (CMF) and Chrysanthemum indicum flower (CIF), two herbs of similar origin, an integrated strategy of network pharmacology, molecular pharmacology, and metabolomics was employed, with a view to investigating the commonalities and dissimilarities in chemical components, efficacy and mechanisms of action. Initial HPLC-Q-TOF-MS analysis revealed that CMF and CIF had different flavonoid constituents. The biological processes underlying the therapeutic effects of CMF and CIF on liver-fire hyperactivity syndrome of hypertension (LFHSH) were predicted to be related to inflammatory response, fatty acid production, and other pathways based on network pharmacology analysis. ELISA, molecular docking, Western blot, and metabolomics techniques showed similar effects of CMF and CIF in lowering blood pressure, resistance to tissue, organ and functional damage, and dyslipidemia. However, distinct effects were found in the regulation of inflammatory response, PI3K-Akt and NF-κB signaling pathways, lipid anabolism, renin-angiotensin system, and metabolic abnormalities. The comparable efficacies of CMF and CIF, despite having distinct mechanisms of action, may be attributed to the integration and counteraction of their different regulating capabilities on the above anti-LFHSH mechanisms. This study offers a vital platform for assessment of differential and precise applications of herbs of close origin with similar but slightly different medicinal properties, and provides a research strategy for bridging Chinese medicine and modern precision medicine.PMID:36430265 | DOI:10.3390/ijms232213767

Int J Mol Sci. 2022 Nov 9;23(22):13782. doi: 10.3390/ijms232213782.ABSTRACTSorghum (Sorghum bicolor) is an important multipurpose crop grown worldwide, but like many other crops, it is often threatened by insect pests. Sugarcane aphid (SCA, Melanaphis sacchari Zehntner), for example, is one of the most severe pests in sorghum, which causes plant damage and yield loss. The main objective of this study was to assess the effect of phytohormones on host plant resistance to aphid attack. Two sorghum genotypes, BTx623 (susceptible) and Tx2783 (resistant), were selected for a comparative analysis of differential expression of a group of phytohormones in response to aphid infestation. The quantification of phytohormones through LC-MS demonstrated higher levels of jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and auxins in the resistant genotype infested with SCA. The PCA plot supports the strong differential responses between resistant and susceptible genotypes, indicating a positive correlation between JA and ABA and a negative correlation between SA and auxins. Similarly, RT-PCR results of the phytohormones-related marker genes showed higher expression in the resistant genotype compared to the susceptible one. Furthermore, to corroborate the role of phytohormones in plant defense, the susceptible genotype was treated with SA, JA, and ABA. The exogenous application of SA and JA + ABA significantly reduced plant mortality, aphid number, and damage in the susceptible genotype, suggesting a strong correlation between phytohormones and plant survival. Our findings indicate that phytohormones play positive roles in plant defense against aphids and provide new insights into the molecular mechanisms operating in plants for self-protection. These findings could also stimulate further research into the mystery about the regulation of phytohormone production during plant interaction with aphids.PMID:36430259 | DOI:10.3390/ijms232213782

Int J Mol Sci. 2022 Nov 9;23(22):13773. doi: 10.3390/ijms232213773.ABSTRACTCisplatin (cDDP)-based chemotherapy is often limited by severe deleterious effects (nephrotoxicity, hepatotoxicity and neurotoxicity). The polynuclear palladium(II) compound Pd2Spermine (Pd2Spm) has emerged as a potential alternative drug, with favorable pharmacokinetic/pharmacodynamic properties. This paper reports on a Nuclear Magnetic Resonance metabolomics study to (i) characterize the response of mice brain and liver to Pd2Spm, compared to cDDP, and (ii) correlate brain-liver metabolic variations. Multivariate and correlation analysis of the spectra of polar and lipophilic brain and liver extracts from an MDA-MB-231 cell-derived mouse model revealed a stronger impact of Pd2Spm on brain metabolome, compared to cDDP. This was expressed by changes in amino acids, inosine, cholate, pantothenate, fatty acids, phospholipids, among other compounds. Liver was less affected than brain, with cDDP inducing more metabolite changes. Results suggest that neither drug induces neuronal damage or inflammation, and that Pd2Spm seems to lead to enhanced brain anti-inflammatory and antioxidant mechanisms, regulation of brain bioactive metabolite pools and adaptability of cell membrane characteristics. The cDDP appears to induce higher extension of liver damage and an enhanced need for liver regeneration processes. This work demonstrates the usefulness of untargeted metabolomics in evaluating drug impact on multiple organs, while confirming Pd2Spm as a promising replacement of cDDP.PMID:36430252 | DOI:10.3390/ijms232213773

Int J Mol Sci. 2022 Nov 8;23(22):13738. doi: 10.3390/ijms232213738.ABSTRACTMetastasis is one of the main obstacles for the treatment and prognosis of breast cancer. In this study, the effects and possible mechanisms of aloe emodin (AE) and emodin (EMD) for inhibiting breast cancer metastasis were investigated via cell metabolomics. First, a co-culture model of MCF-7 and HUVEC cells was established and compared with a traditional single culture of MCF-7 cells. The results showed that HUVEC cells could promote the development of cancer cells to a malignant phenotype. Moreover, AE and EMD could inhibit adhesion, invasion, and angiogenesis and induce anoikis of MCF-7 cells in co-culture model. Then, the potential mechanisms behind AE and EMD inhibition of MCF-7 cell metastasis were explored using a metabolomics method based on UPLC-Q-TOF/MS multivariate statistical analysis. Consequently, 27 and 13 biomarkers were identified in AE and EMD groups, respectively, including polyamine metabolism, methionine cycle, TCA cycle, glutathione metabolism, purine metabolism, and aspartate synthesis. The typical metabolites were quantitatively analyzed, and the results showed that the inhibitory effect of AE was significantly better than EMD. All results confirmed that AE and EMD could inhibit metastasis of breast cancer cells through different pathways. Our study provides an overall view of the underlying mechanisms of AE and EMD against breast cancer metastasis.PMID:36430215 | DOI:10.3390/ijms232213738

Int J Mol Sci. 2022 Nov 8;23(22):13733. doi: 10.3390/ijms232213733.ABSTRACTTuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into three experimental groups-healthy controls (controls), latent TB infection (LTBI), and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate, and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between controls and TB patients. The AUC, specificity, and sensitivity, determined by ROC statistical analysis of the model composed of four of these proteins considering both proteomic sets, were 0.96, 93%, and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine, and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes were submitted to ROC analysis. An AUC = 1 was determined, with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling one protein and four metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature correctly assigned the 12 controls and 12 patients used only for prediction (AUC = 1, specificity = 100%, and sensitivity = 100%). This multiomics approach revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test.PMID:36430211 | DOI:10.3390/ijms232213733

Int J Mol Sci. 2022 Nov 8;23(22):13712. doi: 10.3390/ijms232213712.ABSTRACTSugarcane is the most important sugar crop, contributing ≥80% to total sugar production around the world. Spodoptera frugiperda is one of the main pests of sugarcane, potentially causing severe yield and sugar loss. The identification of key defense factors against S. frugiperda herbivory can provide targets for improving sugarcane resistance to insect pests by molecular breeding. In this work, we used one of the main sugarcane pests, S. frugiperda, as the tested insect to attack sugarcane. Integrated transcriptome and metabolomic analyses were performed to explore the changes in gene expression and metabolic processes that occurred in sugarcane leaf after continuous herbivory by S. frugiperda larvae for 72 h. The transcriptome analysis demonstrated that sugarcane pest herbivory enhanced several herbivory-induced responses, including carbohydrate metabolism, secondary metabolites and amino acid metabolism, plant hormone signaling transduction, pathogen responses, and transcription factors. Further metabolome analysis verified the inducement of specific metabolites of amino acids and secondary metabolites by insect herbivory. Finally, association analysis of the transcriptome and metabolome by the Pearson correlation coefficient method brought into focus the target defense genes against insect herbivory in sugarcane. These genes include amidase and lipoxygenase in amino acid metabolism, peroxidase in phenylpropanoid biosynthesis, and pathogenesis-related protein 1 in plant hormone signal transduction. A putative regulatory model was proposed to illustrate the sugarcane defense mechanism against insect attack. This work will accelerate the dissection of the mechanism underlying insect herbivory in sugarcane and provide targets for improving sugarcane variety resistance to insect herbivory by molecular breeding.PMID:36430189 | DOI:10.3390/ijms232213712

Foods. 2022 Nov 21;11(22):3746. doi: 10.3390/foods11223746.ABSTRACTPea-tea intercropping is an excellent cultivation method that can improve tea quality. However, the underlying mechanism is still unclear. The present study was aimed at elucidating the mechanism of the effect of pea-tea intercropping on tea quality through a high-throughput method. Transcriptome and metabolome analyses were conducted to identify the changes in gene expression and metabolites changes intercropping, respectively. In addition, the amino acids and catechins were detected using the LC-MS method and quantified absolutely. The results showed that total polyphenols and catechins decreased but amino acids increased in pea intercropped tea shoots. Correspondingly, genes related to amino acid metabolism and flavonoid biosynthesis were differentially expressed. For amino acid metabolism, 11 differentially expressed genes were identified, including 5 upregulated and 6 downregulated genes. Meanwhile, three genes involved in carbohydrate transport and metabolism were upregulated in pea intercropped tea plants. These genes were also involved in amino acid metabolism. For flavonoid biosynthesis, two downregulated genes were identified, which were the flavonol synthase and anthocyanidin synthase genes and followed a similar pattern to changes in catechins and polyphenols. These advances have opened new horizons for understanding the biochemical mechanisms of amino acids and flavonoids in improving tea quality in the pea-tea intercropping cultivation model.PMID:36429338 | DOI:10.3390/foods11223746

Foods. 2022 Nov 20;11(22):3731. doi: 10.3390/foods11223731.ABSTRACTGoji berry (Lycium barbarum L., LBL) is a good source of carotenoids, while the bioaccessibility of various types of LBL carotenoids has not been explored. In the study, eight carotenoids, three carotenoid esters and two carotenoid glycosylated derivatives were identified by a non-targeted metabolomics approach. The dried LBL (DRI), LBL in water (WAT), and LBL in "Baijiu" (WIN) were used to recreate the three regularly chosen types of utilization, and the in vitro digestion model showed that the bioaccessibility of the carotenoids increased significantly from the oral to the gastric and intestinal phase (p < 0.05). The bioaccessibility of LBL carotenoids was the most elevated for DRI (at 28.2%), followed by WIN and WAT (at 24.9% and 20.3%, respectively). Among the three carotenoids, zeaxanthin dipalmitate showed the highest bioaccessibility (51.8-57.1%), followed by β-carotene (51.1-55.6%) and zeaxanthin (45.2-56.3%). However, the zeaxanthin from DRI exhibited significantly higher bioaccessibility (up to 58.3%) than WAT and WIN in both the gastric and intestinal phases (p < 0.05). Results of antioxidant activity tests based on DPPH, FRAP, and ABTS showed that the addition of lipids improved the bioaccessibility of the carotenoids. (p < 0.05).PMID:36429323 | DOI:10.3390/foods11223731

Foods. 2022 Nov 18;11(22):3706. doi: 10.3390/foods11223706.ABSTRACTScleroglucan is obtained from Sclerotium rolfsii and is widely used in many fields. In this study, transcriptomics combined with metabolomics were used to study the global metabolites and gene changes. The results of the joint analysis showed that the DEGs (differentially expressed genes) and DEMs (differentially expressed metabolites) of SEPS_48 (fermented with sucrose as a carbon source for 48 h) and GEPS_48 (fermented with glucose as a carbon source for 48 h) comparison groups were mainly related to cell metabolism, focusing on carbohydrate metabolism, amino acid metabolism, and amino sugar and nucleoside sugar metabolism. We therefore hypothesized that the significant differences in these metabolic processes were responsible for the differences in properties. Moreover, the joint analysis provides a scientific theoretical basis for fungal polysaccharides biosynthesis and provides new insights into the effects of carbon sources on the production. As an excellent bioenergy and biological product, scleroglucan can be better applied in different fields, such as the food industry.PMID:36429298 | DOI:10.3390/foods11223706

Foods. 2022 Nov 17;11(22):3677. doi: 10.3390/foods11223677.ABSTRACTA variety of metabolites contribute to the freshness and taste characteristics of seafood. This study investigated the effects of high hydrostatic pressure (HHP; 400, 500, and 600 MPa) for 10 min) on the metabolome of striped prawn during chilled storage, in relation to microorganisms' development. All treated samples showed lower viable counts throughout storage compared to the untreated counterparts. The limit of acceptability from a microbiological point of view was extended from 9 to as many as 35 days by 600 MPa treatment. Metabolites were quantified by 1H-NMR through a targeted-untargeted metabolomic approach. Molecules linked to nucleotides' degradation and amines' anabolism suggested an overall freshness improvement granted by HHP. Notably, putrescine and cadaverine were detected only in untreated prawn samples, suggesting the inactivation of degradative enzymes by HHP. The concentration of molecules that influence umami perception was significantly elevated by HHP, while in untreated samples, the concentration of molecules contributing to a sour taste gradually increased during storage. As metabolomics was applied in its untargeted form, it allowed us to follow the overall set of metabolites related to HHP processing and storage, thus providing novel insights into the freshness and taste quality of striped prawn as affected by high hydrostatic pressure.PMID:36429269 | DOI:10.3390/foods11223677

Pharmacol Res. 2022 Nov 22:106569. doi: 10.1016/j.phrs.2022.106569. Online ahead of print.ABSTRACTPhenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.PMID:36427798 | DOI:10.1016/j.phrs.2022.106569

Drug Discov Today. 2022 Nov 22:103460. doi: 10.1016/j.drudis.2022.103460. Online ahead of print.ABSTRACTMetabolomics enables the comprehensive and unbiased analysis of metabolites and lipids in biological systems. In conjunction with high-throughput activity screening, big data and synthetic biology, metabolomics can guide the discovery of lead compounds with pharmacological activity from natural sources and the gut microbiome. In combination with other omics, metabolomics can further unlock the elucidation of compound toxicity, the mode of action and novel druggable targets of disease. Here, we discuss the workflows, limitations and future opportunities to leverage metabolomics and big data in conjunction with systems and synthetic biology for streamlining the discovery and development of molecules of pharmaceutical interest.PMID:36427778 | DOI:10.1016/j.drudis.2022.103460

Sci Total Environ. 2022 Nov 22:160387. doi: 10.1016/j.scitotenv.2022.160387. Online ahead of print.ABSTRACTMicroplastic contamination of freshwater ecosystems has become an increasing environmental concern. To advance the hazard assessment of microplastics, we conducted a microcosm experiment in which we exposed a simplified aquatic ecosystem consisting of moss and caddisflies to microplastics (polyethylene, polystyrene and polypropylene) and pharmaceuticals and personal care products (1H-benzotriazole, bisphenol A, caffeine, gemfibrozil, ketoprofen, methylparaben, estriol, diphenhydramine, tris (1-chloro-2-propyl) phosphate) over the course of 60 days. We monitored the flux of microplastics within the microcosm, as well as the metabolic and total protein variation of organisms. This study offers evidence highlighting the capacity of moss to act as a sink for free-floating microplastics in freshwater environments. Moss is also shown to serve as a source and pathway for microplastic particles to enter aquatic food webs via caddisflies feeding off of the moss. Although most ingested microparticles were eliminated between caddisflies life stages; however, a small fraction of microplastics was transferred from aquatic to terrestrial ecosystem by emergence. While moss exhibited a mild response to microplastic stress, caddisflies ingesting microplastics showed stress comparable to that caused by exposure to pharmaceuticals. The molecular responses that the stressors triggered were tentatively identified and related to phenotypic responses such as the delayed development manifested through the delayed emergence of caddisflies exposed to stress. Overall, our study provides valuable insights into the adverse effects of microplastics on aquatic species, compares the impacts of microplastics on freshwater biota to those of pharmaceuticals and endocrine disrupting compounds, and demonstrates the role aquatic organisms have in redistributing microplastics between aquatic and terrestrial ecosystems.PMID:36427730 | DOI:10.1016/j.scitotenv.2022.160387

Water Res. 2022 Nov 17;228(Pt A):119377. doi: 10.1016/j.watres.2022.119377. Online ahead of print.ABSTRACTAdaptation to substrate fluctuations is a life actuality of microbes in global municipal wastewater treatment plants (WWTPs). Yet there remains a lack of definite information on how influent changes with different alternation frequencies shape the stability of anammox consortia and the metabolic regulations they feedback. According to human rhythmic activity, day-fluctuant fed (every 6 h, alternating between 50 and 100 mg NH4+-N/L) substantially diminished the robustness of nitrogen removal efficiency (NRE; 84.1 ± 7.0%, left-skewed distribution [R2 = 0.87]) and shock-resistance ability (>30% effluent variability). Unexpectedly, the anammox ecosystem under week-fluctuant mode (every 6 d) displayed adapted growth (NRE 86.6 ± 3.1%, normal distribution [R2 = 0.97]), higher extracellular polymeric substances (EPS) yields, and superior tolerance (juggling the shortest recovery time and highest NRE, tightest protein secondary structure facing long-term load shocks) than steady-state (75 mg NH4+-N/L). 16S sequencing showed that the influent disturbance led to increased levels of bacterial diversity, however, a similar microbiota composition between week-fluctuant and steady systems was detected. Notably, K strategist Candidatus Kuenenia was more sensitive to substrate fluctuations, with the lower relative abundance at day-fluctuant (23.4 ± 5.1%) and week-fluctuant (39.5 ± 4.3%) than at steady-state community (47.5 ± 4.2%). Conversely, Candidatus Jettenia had higher relative abundance at day-fluctuant (i.e., 1.3 ± 0.1%) compared to that at week-fluctuant (0.2 ± 0.04%) and steady-state (0.05 ± 0.03%). Importantly, untargeted metabolomics revealed that week-fluctuant grown anammox microbiota increased protein synthesis and transporter expression while decreasing expression of catabolic pathways (citric acid cycle and bypass) as a strategy for efficient substrate uptake and utilization, which clearly different to day-fluctuant and steady-state survival ways. Overall, we predictively reported an "anabolic adaptation growth state" for the anammox consortia and put forward the associated reinforcement control strategy.PMID:36427463 | DOI:10.1016/j.watres.2022.119377

Sci Immunol. 2022 Nov 25;7(77):eabl9467. doi: 10.1126/sciimmunol.abl9467. Epub 2022 Nov 25.ABSTRACTActivated lymphocytes adapt their metabolism to meet the energetic and biosynthetic demands imposed by rapid growth and proliferation. Common gamma chain (cγ) family cytokines are central to these processes, but the role of downstream signal transducer and activator of transcription 5 (STAT5) signaling, which is engaged by all cγ members, is poorly understood. Using genome-, transcriptome-, and metabolome-wide analyses, we demonstrate that STAT5 is a master regulator of energy and amino acid metabolism in CD4+ T helper cells. Mechanistically, STAT5 localizes to an array of enhancers and promoters for genes encoding essential enzymes and transporters, where it facilitates p300 recruitment and epigenetic remodeling. We also find that STAT5 licenses the activity of two other key metabolic regulators, the mTOR signaling pathway and the MYC transcription factor. Building on the latter, we present evidence for transcriptome-wide cooperation between STAT5 and MYC in both normal and transformed T cells. Together, our data provide a molecular framework for transcriptional programing of T cell metabolism downstream of cγ cytokines and highlight the JAK-STAT pathway in mediating cellular growth and proliferation.PMID:36427325 | DOI:10.1126/sciimmunol.abl9467

Hum Reprod. 2022 Nov 25:deac254. doi: 10.1093/humrep/deac254. Online ahead of print.ABSTRACTSTUDY QUESTION: Can a combination of metabolomic signature and machine learning (ML) models distinguish nonclassic 21-hydroxylase deficiency (NC21OHD) from polycystic ovary syndrome (PCOS) without adrenocorticotrophic hormone (ACTH) testing?SUMMARY ANSWER: A single sampling methodology may be an alternative to the dynamic ACTH test in order to exclude the diagnosis of NC21OHD in the presence of a clinical hyperandrogenic presentation at any time of the menstrual cycle.WHAT IS KNOWN ALREADY: The clinical presentation of patients with NC21OHD is similar with that for other disorders of androgen excess. Currently, cosyntropin stimulation remains the gold standard diagnosis of NC21OHD.STUDY DESIGN, SIZE, DURATION: The study was designed using a bicentric recruitment: an internal training set included 19 women with NC21OHD and 19 controls used for developing the model; a test set included 17 NC21OHD, 72 controls and 266 PCOS patients used to evaluate the performance of the diagnostic strategy thanks to an ML approach.PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifteen steroid species were measured in serum by liquid chromatography-mass spectrometry (LC-MS/MS). This set of 15 steroids (defined as 'steroidome') used to map the steroid biosynthesis pathway was the input for our models.MAIN RESULTS AND THE ROLE OF CHANCE: From a single sample, modeling involving metabolic pathway mapping by profiling 15 circulating steroids allowed us to identify perfectly NC21OHD from a confounding PCOS population. The constructed model using baseline LC-MS/MS-acquired steroid fingerprinting successfully excluded all 17 NC21OHDs (sensitivity and specificity of 100%) from 266 PCOS from an external testing cohort of originally 549 women, without the use of ACTH testing. Blood sampling timing during the menstrual cycle phase did not impact the efficiency of our model.LIMITATIONS, REASONS FOR CAUTION: The main limitations were the use of a restricted and fully prospective cohort as well as an analytical issue, as not all laboratories are equipped with mass spectrometers able to routinely measure this panel of 15 steroids. Moreover, the robustness of our model needs to be established with a larger prospective study for definitive validation in clinical practice.WIDER IMPLICATIONS OF THE FINDINGS: This tool makes it possible to propose a new semiology for the management of hyperandrogenism. The model presents better diagnostic performances compared to the current reference strategy. The management of patients may be facilitated by limiting the use of ACTH tests. Finally, the modeling process allows a classification of steroid contributions to rationalize the biomarker approach and highlight some underlying pathophysiological mechanisms.STUDY FUNDING/COMPETING INTEREST(S): This study was supported by 'Agence Française de Lutte contre le dopage' and DIM Région Ile de France. This study was supported by the French institutional PHRC 2010-AOR10032 funding source and APHP. All authors declare no competing financial interests.TRIAL REGISTRATION NUMBER: N/A.PMID:36427016 | DOI:10.1093/humrep/deac254

ACS Appl Bio Mater. 2022 Nov 25. doi: 10.1021/acsabm.2c00857. Online ahead of print.ABSTRACTUnder healthy physiological conditions, living organisms possess a variety of antioxidant mechanisms to scavenge overproduced reactive oxygen species (ROS). However, under pathological circumstances, endogenous antioxidant systems may not be adequate to eliminate the excessive amount of oxidants, and thus, a continuous exogenous antioxidant income is required. In this regard, sumac (Rhus coriaria) extract is a good candidate for therapeutic applications, because of its high content of antioxidant polyphenolic compounds. In this work, sumac extract-loaded nanosheets (sumac-nanosheet) have been exploited for loading and controlled release of sumac extract, envisioning topical drug delivery applications. Sumac extract has been obtained through the solvent extraction method, and polymeric nanosheets have been thereafter prepared through the spin coating-assisted layer-by-layer deposition of polycaprolactone (PCL), sumac extract, and poly(d,l-lactic acid) (PDLLA). The collected data show a rich content of the sumac extract in terms of polyphenolic compounds, as well as its strong antioxidant properties. Moreover, for the first time in the literature, we demonstrated the possibility of efficiently loading such extract in polymeric nanosheets and the suitability of this nanoplatform as a reactive oxygen species scavenger in human dermal fibroblasts treated with a pro-oxidant insult.PMID:36426992 | DOI:10.1021/acsabm.2c00857

Mol Omics. 2022 Nov 25. doi: 10.1039/d2mo00260d. Online ahead of print.ABSTRACTAtherosclerosis is the principal cause of vascular diseases and one of the leading causes of worldwide death. Even though several insights into its natural course, risk factors and interventions have been identified, it is still an ongoing global pandemic. Since the structure and biochemical composition of the plaques show high heterogeneity, a comprehensive understanding of the intraplaque composition, its microenvironment, and the mechanisms of the progression and instability across different vascular beds at their progression stages is crucial for better risk stratification and treatment modalities. Even though several cell-based studies, animal studies, and extensive multicentric population studies have been conducted concerning cardiovascular diseases for assessing the risk factors and plaque biology, the studies on human clinical samples are very limited. New novel approaches utilize samples from percutaneous coronary interventions, which could possibly gain more access to clinical samples at different stages of the diseases without complex invasive resections. As an emerging technological platform in disease discovery research, mass spectrometry-based omics technologies offer capabilities for a comprehensive understanding of the mechanisms linked to several vascular diseases. Here, we discuss the cellular and molecular processes of atherosclerosis, different mass spectrometry-based omics approaches, and the studies mostly done on clinical samples of atheroma plaque using mass spectrometry-based proteomics, metabolomics and lipidomics approaches.PMID:36426765 | DOI:10.1039/d2mo00260d

Anal Chem. 2022 Nov 25. doi: 10.1021/acs.analchem.2c03986. Online ahead of print.ABSTRACTOne of the technical challenges in the field of metabolomics is the development of a single-run method to detect the full complement of polar metabolites in biological samples. However, an ideal method to meet this demand has not yet been developed. Herein, we proposed a simple methodology that enables the comprehensive and simultaneous analysis of polar metabolites using unified-hydrophilic-interaction/anion-exchange liquid chromatography mass spectrometry (unified-HILIC/AEX/MS) with a polymer-based mixed amines column composed of methacrylate-based polymer particles with primary, secondary, tertiary, and quaternary amines as functional groups. The optimized unified-HILIC/AEX/MS method is composed of two consecutive chromatographic separations, HILIC-dominant separation for cationic, uncharged, and zwitterionic polar metabolites [retention times (RTs) = 0-12.8 min] and AEX-dominant separation for polar anionic metabolites (RTs = 12.8-26.5 min), by varying the ratio of acetonitrile to 40 mM ammonium bicarbonate solution (pH 9.8). A total of 400 polar metabolites were analyzed simultaneously through a combination of highly efficient separation using unified-HILIC/AEX and remarkably sensitive detection using multiple reaction monitoring-based triple quadrupole mass spectrometry (unified-HILIC/AEX/MS/MS). A nontargeted metabolomic approach using unified-HILIC/AEX high-resolution mass spectrometry (unified-HILIC/AEX/HRMS) also provided more comprehensive information on polar metabolites (3242 metabolic features) in HeLa cell extracts than the conventional HILIC/HRMS method (2068 metabolic features). Our established unified-HILIC/AEX/MS/MS and unified-HILIC/AEX/HRMS methods have several advantages over conventional techniques, including polar metabolome coverage, throughput, and accurate quantitative performance, and represent potentially useful tools for in-depth studies on metabolism and biomarker discovery.PMID:36426757 | DOI:10.1021/acs.analchem.2c03986

J Proteome Res. 2022 Nov 25. doi: 10.1021/acs.jproteome.2c00473. Online ahead of print.ABSTRACTBiomarkers are of central importance for assessing the health state and to guide medical interventions and their efficacy; still, they are lacking for most diseases. Mass spectrometry (MS)-based proteomics is a powerful technology for biomarker discovery but requires sophisticated bioinformatics to identify robust patterns. Machine learning (ML) has become a promising tool for this purpose. However, it is sometimes applied in an opaque manner and generally requires specialized knowledge. To enable easy access to ML for biomarker discovery without any programming or bioinformatics skills, we developed "OmicLearn" (http://OmicLearn.org), an open-source browser-based ML tool using the latest advances in the Python ML ecosystem. Data matrices from omics experiments are easily uploaded to an online or a locally installed web server. OmicLearn enables rapid exploration of the suitability of various ML algorithms for the experimental data sets. It fosters open science via transparent assessment of state-of-the-art algorithms in a standardized format for proteomics and other omics sciences.PMID:36426751 | DOI:10.1021/acs.jproteome.2c00473