PubMed

Molecules. 2023 Jan 1;28(1):351. doi: 10.3390/molecules28010351.ABSTRACTThe genus Ulex comprises thirteen accepted species of perennial shrubs in the family Fabaceae. In Galicia (Spain) many of these are considered spontaneous colonizing species, which are easy to establish and maintain. Among them, Ulex gallii Planch. is used in traditional medicine for the same anti-infective, hypotensive and diuretic purposes as Ulex europaeus L., which is the most studied species. Likewise, some studies have described the antitumoral properties of several species. However, there are few scientific studies that justify the use of Ulex gallii Planch. and nothing has been reported about its composition to date. In our study, the entire plant was extracted with methanol and the crude extract was subjected to liquid phase extraction with distinct solvents, yielding three fractions: hexane (H), dichloromethane (D) and methanol (M), which were subsequently fractionated. The dichloromethane (D5, D7 and D8) and methanol (M4) sub-fractions showed antiproliferative activity on A549 (lung cancer) and AGS (stomach cancer) cell lines, and caspase 3/7 activity assessment and DNA quantification were also performed. Targeted analysis via UHPLC-QToF, in combination with untargeted analysis via MS-Dial, MS-Finder and Global Natural Products Social Molecular Networking (GNPS), allowed us to tentatively identify different metabolites in these sub-fractions, mostly flavonoids, that might be involved in their antiproliferative activity.PMID:36615543 | DOI:10.3390/molecules28010351

Molecules. 2022 Dec 26;28(1):218. doi: 10.3390/molecules28010218.ABSTRACTChemical epigenetic regulation (CER) is an effective method to activate the silent pathway of fungal secondary metabolite synthesis. However, conventional methods for CER study are laborious and time-consuming. In the meantime, the overall profile of the secondary metabolites in the fungi treated by the CER reagent is not well characterized. In this study, suberohydroxamic acid (SBHA), a histone deacetylase inhibitor, was added to a culture of Aspergillus aculeatus DL1011 and a new strategy based on LC-MS/MS analysis integrated with various metabolomic tools (MetaboAnalyst, MS-DIAL, SIRIUS and GNPS) was developed to characterize the profile of induced metabolites. As a result, 13.6%, 29.5% and 27.2% of metabolites were identified as newly biosynthesized, increasing and decreasing in abundance by CER, respectively. The structures of the 18 newly induced secondary metabolites were further identified by the new strategy to demonstrate that 72.2% of them (1 novel compound and 12 known compounds) were first discovered in A. aculeatus upon SBHA treatment. The accuracy of the new approach was confirmed by purification and NMR data analysis of major newly biosynthesized secondary metabolites. The bioassay showed that the newly biosynthesized compounds, roseopurpurin analogues, showed selective activities against DPPH scavenging, cytotoxicity and SHP1 inhibition. Our research demonstrated that CER was beneficial for changing the secondary metabolic profile of fungi and was an effective means of increasing the diversity of active metabolites. Our work also supplied a metabolomic strategy to characterize the profile changes and determine the newly induced compounds in the secondary metabolites of fungi treated with the chemical epigenetic regulator.PMID:36615412 | DOI:10.3390/molecules28010218

Molecules. 2022 Dec 22;28(1):93. doi: 10.3390/molecules28010093.ABSTRACTSalvia fruticosa and S. pomifera subsp. calycina are native to Eastern Mediterranean and S. pomifera subsp. pomifera is endemic to Greece. The primary aim of this study was to develop an analytical methodology for metabolomic profiling and to study their efficacy in combating glycation, the major biochemical complication of diabetes. After sequential ultrasound-assisted extraction of 2 g of leaves with petroleum ether and 70% methanol, the volatile metabolites in the petroleum ether extracts were studied with GC-MS (Gas Chromatography-Mass Spectrometry), whereas the polar metabolites in the hydroalcoholic extracts were determined and quantified by UHPLC-DAD-ESI-MS (Ultra-High Performance Liquid Chromatography-Diode Array Detector-Mass Spectrometry). This methodology was applied to five populations belonging to the three native taxa. 1,8-Cineole was the predominant volatile (34.8-39.0%) in S. fruticosa, while S. pomifera had a greater content of α-thujone (19.7-41.0%) and β-thujone (6.0-39.1%). Principal Component Analysis (PCA) analysis of the volatiles could discriminate the different taxa. UHPLC-DAD-ESI-MS demonstrated the presence of 50 compounds, twenty of which were quantified. PCA revealed that not only the taxa but also the populations of S. pomifera subsp. pomifera could be differentiated. All Salvia samples inhibited advanced glycation end-product formation in a bovine serum albumin/2-deoxyribose assay; rosmarinic and carnosic acid shared this activity. This study demonstrates the antiglycation activity of S. fruticosa and S. pomifera extracts for the first time and presents a miniaturized methodology for their metabolomic profiling, which could aid chemotaxonomic studies and serve as a tool for their authentication and quality control.PMID:36615289 | DOI:10.3390/molecules28010093

Molecules. 2022 Dec 22;28(1):83. doi: 10.3390/molecules28010083.ABSTRACTTetrastigma hemsleyanum Diels et Gilg, known as a "plant antibiotic", possesses several attractive properties including anti-inflammatory, anti-tumor, and antioxidant effects, with its efficacy being attributed to flavonoids. However, the flavonoid biosynthesis of T. hemsleyanum has rarely been studied. In this study, we investigated the flavonoid metabolism of T. hemsleyanum through metabolome analysis and transcriptome sequencing. The metabolomic results showed differences in the flavonoids of the leaves and root tubers of T. hemsleyanum. A total of 22 flavonoids was detected, and the concentrations of most flavonoids in the leaves were higher than those in the root tubers. Transcriptome analysis revealed that differentially expressed genes (DEGs) in the leaves and root tubers were enriched in photosynthesis-antenna proteins. Pearson correlation analysis indicated that the expression levels of chalcone isomerase (CHI) and UDP-glycose flavonoid glycosyltransferase (UFGT) were highly correlated with the concentrations of most flavonoids. Further, this study found that the photosynthesis-antenna proteins essentially contributed to the difference in the flavonoids in T. hemsleyanum. The gene expressions and concentrations of the total flavonoids of leaves and root tubers in Hangzhou, Jinhua, Lishui, and Taizhou in Zhejiang Province, China, showed that CHI (CL6715.Contig1_All, Unigene19431_All, CL921.Contig4_All) and UFGT (CL11556.Contig3_All, CL11775.Contig1_All) were the potential key genes of accumulation of most flavonoids in T. hemsleyanum.PMID:36615276 | DOI:10.3390/molecules28010083

Molecules. 2022 Dec 21;28(1):25. doi: 10.3390/molecules28010025.ABSTRACTPolygonum multiflorum Thunb. (PMT), a commonly used Chinese herbal medicine for treating diseases such as poisoning and white hair, has attracted constant attention due to the frequent occurrence of liver injury incidents. To date, its hepatotoxic equivalent markers (HEMs) and potential hepatotoxic mechanisms are still unclear. In order to clarify the HEMs of PMT and further explore the potential mechanisms of hepatotoxicity, firstly, the chemical constituents in PMT extract were globally characterized, and the fingerprints of PMT extracts were established along with the detection of their hepatotoxicity in vivo. Then, the correlations between hepatotoxic features and component contents were modeled by chemometrics to screen HEMs of PMT, which were then further evaluated. Finally, the hepatotoxic mechanisms of PMT were investigated using liver metabolomics and molecular docking. The results show that the chemical combination of 2,3,5,4-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) and emodin-8-O-glucoside (EG) was discovered as the HEMs of PMT through pre-screening and verifying process. Liver metabolomics revealed that PMT caused liver injury by interfering with purine metabolism, which might be related to mitochondrial function disorder and oxidative injury via the up-regulations of xanthosine and xanthine, and the down-regulation of 5' nucleotidase (NT5E) and adenylate kinase 2 (AK2). This study not only found that the HEMs of PMT were TSG and EG, but also clarified that PMT might affect purine metabolism to induce liver injury, which contributed to our understanding of the underlying mechanisms of PMT hepatotoxicity.PMID:36615221 | DOI:10.3390/molecules28010025

Molecules. 2022 Dec 20;28(1):9. doi: 10.3390/molecules28010009.ABSTRACTAmerican ginseng (Panax quinquefolius L.) has been recognized as a valuable herb medicine, and ginsenosides are the most important components responsible for the health-beneficial effects. This study investigated the secondary metabolites responsible for the differentiation of wild and cultivated American ginsengs with ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic approach. An in-house ginsenoside library was developed to facilitate data processing and metabolite identification. Data visualization methods, such as heatmaps and volcano plots, were utilized to extract discriminated ion features. The results suggested that the ginsenoside profiles of wild and cultivated ginsengs were significantly different. The octillol (OT)-type ginsenosides were present in greater abundance and diversity in wild American ginsengs; however, a wider distribution of the protopanaxadiol (PPD)-and oleanolic acid (OA)-type ginsenosides were found in cultivated American ginseng. Based on the tentative identification and semi-quantification, the amounts of five ginsenosides (i.e., notoginsenoside H, glucoginsenoside Rf, notoginsenoside R1, pseudoginsenoside RT2, and ginsenoside Rc) were 2.3-54.5 fold greater in wild ginseng in comparison to those in their cultivated counterparts, and the content of six ginsenosides (chicusetsusaponin IVa, malonylginsenoside Rd, pseudoginsenoside Rc1, malonylfloralginsenoside Rd6, Ginsenoside Rd, and malonylginsenoside Rb1) was 2.6-14.4 fold greater in cultivated ginseng compared to wild ginseng. The results suggested that the in-house metabolite library can significantly reduce the complexity of the data processing for ginseng samples, and UHPLC-HRMS is effective and robust for identifying characteristic components (marker compounds) for distinguishing wild and cultivated American ginseng.PMID:36615206 | DOI:10.3390/molecules28010009

J Clin Med. 2022 Dec 31;12(1):332. doi: 10.3390/jcm12010332.ABSTRACTINTRODUCTION: The bicuspid aortic valve (BAV) confers a high risk of ascending aorta dilatation (AAoD), although its progression seems highly variable. Furthermore, the implication of lipoprotein metabolism and inflammation in the mechanisms that underlie AAoD is not fully established. The aim of this study consisted of evaluating the impact of the lipoprotein and glycoprotein profiles in AAOD as well as its progression in BAV aortopathy.METHODS: Using 1H-nuclear magnetic resonance (1H-NMR), we analyzed and compared the lipoprotein and glycoprotein profiles of plasma samples from 152 BAV patients with dilated and nondilated ascending aorta. Additionally, these profiles were also compared for 119 of these patients who were prospectively followed-up clinically and by echocardiography in the long-term (5 years). Ascending aorta dilation velocity (mm/year) was calculated for this analysis.RESULTS: Several parameters related to the lipoprotein profile including remnant cholesterol, small LDL and IDL-cholesterol were found to be significantly increased in the dilated group compared to those in the nondilated group. The glycoprotein A-nuclear magnetic resonance (NMR) signal, a novel inflammation biomarker, was also observed to be increased in the dilated group. After performing multivariate analysis, remnant cholesterol remained an independent variable related to AAoD. In the long-term follow-up, proatherogenic lipoprotein parameters were related to ascending aorta dilatation velocity ascending. After a lineal regression analysis, non-HDL particles remained as an independent predictor of ascending aorta dilation velocity.CONCLUSIONS: Patients with BAV and AAoD presented a more pro-atherogenic profile assessed by 1H-NMR, especially related to triglyceride-rich lipoproteins. This pro-atherogenic profile seems to contribute to the higher growth rate of ascending aorta diameter.PMID:36615132 | DOI:10.3390/jcm12010332

Int J Mol Sci. 2023 Jan 3;24(1):890. doi: 10.3390/ijms24010890.ABSTRACTNotwithstanding the great improvement of ART, the overall rate of successful pregnancies from implanted human embryos is definitely low. The current routine embryo quality assessment is performed only through morphological criteria, which has poor predictive capacity since only a minor percentage of those in the highest class give rise to successful pregnancy. Previous studies highlighted the potentiality of the analysis of metabolites in human embryo culture media, useful for the selection of embryos for implantation. In the present study, we analyzed in blind 66 human embryo culture media at 5 days after in vitro fertilization with the aim of quantifying compounds released by cell metabolism that were not present as normal constituents of the human embryo growth media, including purines, pyrimidines, nitrite, and nitrate. Only some purines were detectable (hypoxanthine and uric acid) in the majority of samples, while nitrite and nitrate were always detectable. When matching biochemical results with morphological evaluation, it was found that low grade embryos (n = 12) had significantly higher levels of all the compounds of interest. Moreover, when matching biochemical results according to successful (n = 17) or unsuccessful (n = 25) pregnancy, it was found that human embryos from the latter group released higher concentrations of hypoxanthine, uric acid, nitrite, and nitrate in the culture media. Additionally, those embryos that developed into successful pregnancies were all associated with the birth of healthy newborns. These results, although carried out on a relatively low number of samples, indicate that the analysis of the aforementioned compounds in the culture media of human embryos is a potentially useful tool for the selection of embryos for implantation, possibly leading to an increase in the overall rate of ART.PMID:36614333 | DOI:10.3390/ijms24010890

Int J Mol Sci. 2023 Jan 1;24(1):732. doi: 10.3390/ijms24010732.ABSTRACTPhytic acid (PA) is a strong anti-nutritional factor with a key antioxidant role in countering reactive oxygen species. Despite the potential benefits of low phytic acid (lpa) mutants, the reduction of PA causes pleiotropic effects, e.g., reduced seed germination and viability loss related to seed ageing. The current study evaluated a historical series of naturally aged seeds and showed that lpa1-1 seeds aged faster as compared to wildtype. To mimic natural ageing, the present study set up accelerated ageing treatments at different temperatures. It was found that incubating the seeds at 57 °C for 24 h, the wildtype germinated at 82.4% and lpa1-1 at 40%. The current study also hypothesized two possible solutions to overcome these problems: (1) Classical breeding was used to constitute synthetic populations carrying the lpa1-1 mutation, with genes pushing anthocyanin accumulation in the embryo (R-navajo allele). The outcome showed that the presence of R-navajo in the lpa1-1 genotype was not able to improve the germinability (-20%), but this approach could be useful to improve the germinability in non-mutant genotypes (+17%). (2) In addition, hydropriming was tested on lpa1-1 and wildtype seeds, and germination was improved by 20% in lpa1-1, suggesting a positive role of seed priming in restoring germination. Moreover, the data highlighted metabolic differences in the metabolome before and after hydropriming treatment, suggesting that the differences in germination could also be mediated by differences in the metabolic composition induced by the mutation.PMID:36614175 | DOI:10.3390/ijms24010732

Int J Mol Sci. 2022 Dec 31;24(1):707. doi: 10.3390/ijms24010707.ABSTRACTMetabolites produced by an altered gut microbiota might mediate the effects in the brain. Among metabolites, the fecal volatile organic compounds (VOCs) are considered to be potential biomarkers. In this study, we examined both the VOCs and bacterial taxa in the feces from healthy subjects and Alzheimer's disease (AD) patients at early and middle stages. Remarkably, 29 fecal VOCs and 13 bacterial genera were differentiated from the healthy subjects and the AD patients. In general, higher amounts of acids and esters were found in in the feces of the AD patients and terpenes, sulfur compounds and aldehydes in the healthy subjects. At the early stage of AD, the most relevant VOCs with a higher abundance were short-chain fatty acids and their producing bacteria, Faecalibacterium and Lachnoclostridium. Coinciding with the development of dementia in the AD patients, parallel rises of heptanoic acid and Peptococcus were observed. At a more advanced stage of AD, the microbiota and volatiles shifted towards a profile in the feces with increases in hexanoic acid, Ruminococcus and Blautia. The most remarkable VOCs that were associated with the healthy subjects were 4-ethyl-phenol and dodecanol, together with their possible producers Clostridium and Coprococcus. Our results revealed a VOCs and microbiota crosstalk in AD development and their profiles in the feces were specific depending on the stage of AD. Additionally, some of the most significant fecal VOCs identified in our study could be used as potential biomarkers for the initiation and progression of AD.PMID:36614151 | DOI:10.3390/ijms24010707

Int J Mol Sci. 2022 Dec 30;24(1):620. doi: 10.3390/ijms24010620.ABSTRACTPeriodontitis is a non-communicable chronic inflammatory disease characterized by the progressive and irreversible breakdown of the soft periodontal tissues and resorption of teeth-supporting alveolar bone. The etiology of periodontitis involves dysbiotic shifts in the diversity of microbial communities inhabiting the subgingival crevice, which is dominated by anaerobic Gram-negative bacteria, including Porphyromonas gingivalis. Indeed, P. gingivalis is a keystone pathogen with a repertoire of attributes that allow it to colonize periodontal tissues and influence the metabolism, growth rate, and virulence of other periodontal bacteria. The pathogenic potential of P. gingivalis has been traditionally analyzed using classical biochemical and molecular approaches. However, the arrival of new techniques, such as whole-genome sequencing, metagenomics, metatranscriptomics, proteomics, and metabolomics, allowed the generation of high-throughput data, offering a suitable option for bacterial analysis, allowing a deeper understanding of the pathogenic properties of P. gingivalis and its interaction with the host. In the present review, we revise the use of the different -omics technologies and techniques used to analyze bacteria and discuss their potential in studying the pathogenic potential of P. gingivalis.PMID:36614064 | DOI:10.3390/ijms24010620

Int J Mol Sci. 2022 Dec 29;24(1):609. doi: 10.3390/ijms24010609.ABSTRACTFreezing severely impacts potato production. Deciphering the pathways and metabolites that regulate the freezing tolerance of potato is useful in cultivation and breeding for hardiness. In the present study, Solanum acaule was identified to be more freezing tolerant than S. tuberosum. Furthermore, the two genotypes before/after exposure to 4 °C for 7 d with additional -1 °C for 12 h were analysed by RNA-seq and metabolomics, and the results were compared with the previous -1 °C for 12 h. The results showed that S. acaule activated numerous genes that differed from those of S. tuberosum. Among the genes, five pathways, such as the hormone signalling pathway, which includes salicylic acid, were enriched. Further metabolomics analysis showed that the content of salicylic acid was improved in S. acaule in response to -1 °C for 12 h. Moreover, exogenous application of 0.1 mM salicylic acid to potato was shown to improve constitutive freezing tolerance and increase the expression of HSFC1. Following transcriptome and metabolome analyses, it was documented that the content of SA that increased in freezing-tolerant S. acaule after exposure to cold condition, associated with the SA signalling pathway, enhanced potato freezing tolerance, probably through HSFC1.PMID:36614052 | DOI:10.3390/ijms24010609

Int J Mol Sci. 2022 Dec 29;24(1):602. doi: 10.3390/ijms24010602.ABSTRACTEpidermal growth factor receptor (EGFR) triple mutations with exon 19 deletion (del19), T790M, and cis-C797S (del19/T790M/cis-C797S mutations) frequently occur in patients with non-small cell lung cancer (NSCLC), while progression to frontline EGFR-tyrosine kinase inhibitors (TKIs) and osimertinib was resistant to all clinically available EGFR-TKIs. Brigatinib monotherapy may be a potential treatment for NSCLC harboring del19/T790M/cis-C797S mutations based on preclinical studies; however, no clinical report has evaluated its efficacy on EGFR del19/T790M/cis-C797S mutations. Herein, we present a case of a female patient with EGFR del19-mutated NSCLC treated with afatinib followed by osimertinib due to acquired T790M mutation. The EGFR del19/T790M/cis-C797S mutations were detected following osimertinib treatment. Complete response of skull metastasis was confirmed after brigatinib treatment (90 mg daily). Unfortunately, she experienced intolerable adverse events; therefore, brigatinib was discontinued after three-month usage. This report provides the first reported evidence for the use of brigatinib monotherapy in patients with NSCLC harboring EGFR del19/T790M/cis-C797S mutations after progression to previous EGFR-TKIs.PMID:36614045 | DOI:10.3390/ijms24010602

Int J Mol Sci. 2022 Dec 29;24(1):584. doi: 10.3390/ijms24010584.ABSTRACTThe human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient's macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis.PMID:36614027 | DOI:10.3390/ijms24010584

Int J Mol Sci. 2022 Dec 28;24(1):537. doi: 10.3390/ijms24010537.ABSTRACTPrimary liver cancer is a heterogeneous disease. Liver cancer metabolism includes both the reprogramming of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment and fluctuations in regular tissue metabolism. Currently, metabolomics and metabolite profiling in liver cirrhosis, liver cancer, and hepatocellular carcinoma (HCC) have been in the spotlight in terms of cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecules, chemicals, and metabolites. Metabolomics technologies can provide critical information about the liver cancer state. Here, we review how liver cirrhosis, liver cancer, and HCC therapies interact with metabolism at the cellular and systemic levels. An overview of liver metabolomics is provided, with a focus on currently available technologies and how they have been used in clinical and translational research. We also list scalable methods, including chemometrics, followed by pathway processing in liver cancer. We conclude that important drivers of metabolomics science and scientific technologies are novel therapeutic tools and liver cancer biomarker analysis.PMID:36613980 | DOI:10.3390/ijms24010537

Int J Mol Sci. 2022 Dec 28;24(1):518. doi: 10.3390/ijms24010518.ABSTRACTSalt stress is an unfavorable outcome of global climate change, adversely affecting crop growth and yield. It is the second-biggest abiotic factor damaging the morphological, physio-biochemical, and molecular processes during seed germination and plant development. Salt responses include modulation of hormonal biosynthesis, ionic homeostasis, the antioxidant defense system, and osmoprotectants to mitigate salt stress. Plants trigger salt-responsive genes, proteins, and metabolites to cope with the damaging effects of a high salt concentration. Enhancing salt tolerance among crop plants is direly needed for sustainable global agriculture. Novel protein markers, which are used for crop improvement against salt stress, are identified using proteomic techniques. As compared to single-technique approaches, the integration of genomic tools and exogenously applied chemicals offers great potential in addressing salt-stress-induced challenges. The interplay of salt-responsive proteins and genes is the missing key of salt tolerance. The development of salt-tolerant crop varieties can be achieved by integrated approaches encompassing proteomics, metabolomics, genomics, and genome-editing tools. In this review, the current information about the morphological, physiological, and molecular mechanisms of salt response/tolerance in crops is summarized. The significance of proteomic approaches to improve salt tolerance in various crops is highlighted, and an integrated omics approach to achieve global food security is discussed. Novel proteins that respond to salt stress are potential candidates for future breeding of salt tolerance.PMID:36613963 | DOI:10.3390/ijms24010518

Int J Mol Sci. 2022 Dec 27;24(1):452. doi: 10.3390/ijms24010452.ABSTRACTDrought is one of the most important factors affecting plant growth and production due to ongoing global climate change. Elymus sibiricus has been widely applied for ecological restoration and reseeding of degraded grassland in the Qinghai-Tibetan Plateau (QTP) because of its strong adaptability to barren, salted, and drought soils. To explore the mechanism of drought resistance in E. sibiricus, drought-tolerant and drought-sensitive genotypes of E. sibiricus were used in metabolomic studies under simulated long-term and short-term drought stress. A total of 1091 metabolites were detected, among which, 27 DMs were considered to be the key metabolites for drought resistance of E. sibiricus in weighted gene co-expression network analysis (WGCNA). Ten metabolites, including 3-amino-2-methylpropanoic acid, coniferin, R-aminobutyrate, and so on, and 12 metabolites, including L-Proline, L-histidine, N-acetylglycine, and so on, showed differential accumulation patterns under short-term and long-term drought stress, respectively, and thus, could be used as biomarkers for drought-tolerant and drought-sensitive E. sibiricus. In addition, different metabolic accumulation patterns and different drought response mechanisms were also found in drought-tolerant and drought-sensitive genotypes of E. sibiricus. Finally, we constructed metabolic pathways and metabolic patterns for the two genotypes. This metabolomic study on the drought stress response of E. sibiricus can provide resources and a reference for the breeding of new drought-tolerant cultivars of E. sibiricus.PMID:36613896 | DOI:10.3390/ijms24010452

Int J Mol Sci. 2022 Dec 26;24(1):405. doi: 10.3390/ijms24010405.ABSTRACTThe influence of monochromatic green light stimulation on hatching performance and embryo development has been studied in chickens, but not geese. The liver has crucial functions in the regulation of energy metabolism during embryogenesis, but its involvement in green light transduction is still unidentified. We aimed to determine the influence of monochromatic green light on Yangzhou goose hatching performance and embryo development. We also investigated the metabolomics and transcriptomic responses of the embryonic liver to green light to determine the underlying molecular mechanisms. Eggs were incubated under either 12 h of monochromatic green light/dark (12 L:12D) cycles or 24 h of darkness (0G:24D). Green light promoted embryonic development and hatching performance, also affected the expression of myogenic regulatory factors associated with muscle development. It also shortened hatching time and elevated plasma levels of growth hormone and insulin-like growth factor-1. Metabolomics and transcriptomic results revealed differentially expressed genes and metabolites with enhanced gluconeogenesis/glycolysis and increased plasma glucose and pyruvate levels under green light. Hence, the growth-promoting effect possibly through regulating energy metabolism in the liver and myogenic regulatory factors in muscle. Our findings provide important and novel insights into the mechanisms underlying the beneficial effects of green light on goose embryos.PMID:36613849 | DOI:10.3390/ijms24010405

Int J Mol Sci. 2022 Dec 26;24(1):394. doi: 10.3390/ijms24010394.ABSTRACTMeningiomas (MGMs) are currently classified into grades I, II, and III. High-grade tumors are correlated with decreased survival rates and increased recurrence rates. The current grading classification is based on histological criteria and determined only after surgical tumor sampling. This study aimed to identify plasma metabolic alterations in meningiomas of different grades, which would aid surgeons in predefining the ideal surgical strategy. Plasma samples were collected from 51 patients with meningioma and classified into low-grade (LG) (grade I; n = 43), and high-grade (HG) samples (grade II, n = 5; grade III, n = 3). An untargeted metabolomic approach was used to analyze plasma metabolites. Statistical analyses were performed to select differential biomarkers among HG and LG groups. Metabolites were identified using tandem mass spectrometry along with database verification. Five and four differential biomarkers were identified for HG and LG meningiomas, respectively. To evaluate the potential of HG MGM metabolites to differentiate between HG and LG tumors, a receiving operating characteristic curve was constructed, which revealed an area under the curve of 95.7%. This indicates that the five HG MGM metabolites represent metabolic alterations that can differentiate between LG and HG meningiomas. These metabolites may indicate tumor grade even before the appearance of histological features.PMID:36613836 | DOI:10.3390/ijms24010394

Int J Mol Sci. 2022 Dec 25;24(1):348. doi: 10.3390/ijms24010348.ABSTRACTGlioblastoma (GB) is a primary malignancy of the central nervous system that is classified by the WHO as a grade IV astrocytoma. Despite decades of research, several aspects about the biology of GB are still unclear. Its pathogenesis and resistance mechanisms are poorly understood, and methods to optimize patient diagnosis and prognosis remain a bottle neck owing to the heterogeneity of the malignancy. The field of omics has recently gained traction, as it can aid in understanding the dynamic spatiotemporal regulatory network of enzymes and metabolites that allows cancer cells to adjust to their surroundings to promote tumor development. In combination with other omics techniques, proteomic and metabolomic investigations, which are a potent means for examining a variety of metabolic enzymes as well as intermediate metabolites, might offer crucial information in this area. Therefore, this review intends to stress the major contribution these tools have made in GB clinical and preclinical research and highlights the crucial impacts made by the integrative "omics" approach in reducing some of the therapeutic challenges associated with GB research and treatment. Thus, our study can purvey the use of these powerful tools in research by serving as a hub that particularly summarizes studies employing metabolomics and proteomics in the realm of GB diagnosis, treatment, and prognosis.PMID:36613792 | DOI:10.3390/ijms24010348