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

PubMed

CDK4/6 inhibition in hormone receptor-positive/HER2-negative breast cancer: Biological and clinical aspects

Sat, 14/10/2023 - 12:00
Cytokine Growth Factor Rev. 2023 Oct 5:S1359-6101(23)00075-8. doi: 10.1016/j.cytogfr.2023.10.001. Online ahead of print.ABSTRACTA dysregulated cell division, one of the key hallmarks of cancer, results in uncontrolled cellular proliferation. This aberrant process, mediated by a dysregulated cell-cycle machinery and overactivation of cyclin-dependent kinase (CDK) 4 and 6, can potentially promote tumorigenesis. The clinical application of CDK 4/6 inhibitors, developed to inhibit cell-cycle progression, in the treatment regimens of breast cancer (BC) patients is expanding. Currently, three agents, ribociclib, palbociclib, and abemaciclib, are approved for treating patients with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic BC. In addition, abemaciclib is FDA and EMA-approved for patients with hormone receptor-positive HER2-negative, node-positive, early BC at high risk of recurrence. Emerging data suggest potential anti-tumor effects beyond cell cycle arrest, providing novel insights into the agent's mechanisms of action. As a result, a broader application of the CDK4/6 inhibitors in patients with cancer is achieved, contributing to enhanced optimized treatment in the adjuvant and neoadjuvant settings. Herein, the immunomodulatory activities of CDK4/6 inhibitors, their impact on the cell's metabolic state, and the effect on the decision of the cell to undergo quiescence or senescence are discussed. Moreover, this review provides an update on clinical trial outcomes and the differences in the underlying mechanisms between the distinct CDK4/6 inhibitors.PMID:37838584 | DOI:10.1016/j.cytogfr.2023.10.001

Maize (Zea mays L.) root exudation profiles change in quality and quantity during plant development - a field study

Sat, 14/10/2023 - 12:00
Plant Sci. 2023 Oct 12:111896. doi: 10.1016/j.plantsci.2023.111896. Online ahead of print.ABSTRACTDeciphering root exudate composition of soil-grown plants is considered a crucial step to better understand plant-soil-microbe interactions affecting plant growth performance. In this study, two genotypes of Zea mays L. (WT, rth3) differing in root hair elongation were grown in the field in two substrates (sand, loam) in custom-made, perforated columns inserted into the field plots. Root exudates were collected at different plant developmental stages (BBCH 14, 19, 59, 83) using a soil-hydroponic-hybrid exudation sampling approach. Exudates were characterized by LC-MS based non-targeted metabolomics, as well as by spectrophotometric assays targeting total dissolved organic carbon, soluble carbohydrates, proteins, amino acids, and phenolics. Results showed that plant developmental stage was the main driver for the composition and quantity of exuded compounds. Carbon (C) exudation per plant increased with increasing biomass production over time, while C exudation rates per cm² root surface area h-1 decreased with plant maturity. Furthermore, exudation rates were higher in the substrate with lower nutrient mobility (i.e., loam). Surprisingly, we observed higher exudation rates in root hairless rth3 compared to the root hair-forming WT sibling, though exudate metabolite composition remained similar. Our results highlight the impact of plant developmental stage on the plant-soil-microbe interplay.PMID:37838155 | DOI:10.1016/j.plantsci.2023.111896

Integrative proteome and metabolome analyses reveal molecular basis underlying growth and nutrient composition in the Pacific oyster, Crassostrea gigas

Sat, 14/10/2023 - 12:00
J Proteomics. 2023 Oct 12:105021. doi: 10.1016/j.jprot.2023.105021. Online ahead of print.ABSTRACTIn order to comprehend the molecular basis of growth, nutrient composition, and color pigmentation in oysters, comparative proteome and metabolome analyses of two selectively bred oyster strains with contrasting growth rate and shell color were used in this study. A total of 289 proteins and 224 metabolites were identified differentially expressed between the two strains. We identified a series of specifically enriched functional clusters implicated in protein biosynthesis (RPL4, MRPS7, and CARS), fatty acid metabolism (ACSL5, PEX3, ACOXI, CPTIA, FABP6, and HSD17B12), energy metabolism (FH, PPP1R7, CLAM2, and RGN), cell proliferation (MYB, NFYC, DOHH, TOP2a, SMARCA5, and SMARCC2), material transport (ABCB1, ABCB8, VPS16, and VPS33a), and pigmentation (RDH7, RDH13, Retsat, COX15, and Cyp3a9). Integrated proteome and metabolome analyses indicate that fast-growing strain utilize energy-efficient mechanisms of ATP generation while promoting protein and polyunsaturated fatty acid synthesis, activating the cell cycle to increase cell proliferation and thus promoting their biomass increase. These results uncovered molecular mechanisms underlying growth regulation, nutrition quality, and pigmentation and provided candidate biomarkers for molecular breeding in oysters. SIGNIFICANCE: Rapid growth has always been the primary breeding objective to increase the production profits of Pacific oyster (Crassostrea gigas), while favorable nutritional quality and beautiful color add commercial value. In recent years, proteomic and metabolomic techniques have been widely used in marine organisms, although these techniques are seldom utilized to study oyster growth and development. In this study, two C. gigas strains with contrasted phenotypes in growth and shell color provided an ideal model for unraveling the molecular basis of growth and nutrient composition through a comparison of the proteome and metabolome. Since proteins and metabolites are the critical undertakers and the end products of cellular regulatory processes, identifying the differentially expressed proteins and metabolites would allow for discovering biomarkers and pathways that were implicated in cell growth, proliferation, and other critical functions. This work provides valuable resources in assistance with molecular breeding of oyster strains with superior production traits of fast-growth and high-quality nutrient value.PMID:37838097 | DOI:10.1016/j.jprot.2023.105021

Study on the effect of calibration standards prepared with different matrix on the accuracy of bile acid quantification using LC-MS/MS

Sat, 14/10/2023 - 12:00
J Pharm Biomed Anal. 2023 Oct 10;237:115785. doi: 10.1016/j.jpba.2023.115785. Online ahead of print.ABSTRACTThe transition from relative to absolute quantification of metabolites is the future development trend of mass spectrometry-based metabolomics research, which could fundamentally solve the problem of comparability of data between different laboratories. However, absolute quantification of endogenous molecules is largely hampered by the lack of analyte-free matrix, leading to uncertainty and inconsistency in the preparation of calibration standards. Bile acids (BAs) are an important class of biomarkers that play a key role in disease progression. In this paper, the quantitative accuracy of calibration curves prepared in neat solvent (NSCCs), charcoal stripped matrix (SMCCs) and authentic matrix (AMCCs) were validated using quality control samples (QCs) prepared in authentic matrix. Results suggested that AMCCs could largely minimize the confidence interval (C.I.) and the deviation in accuracy compared with NSCCs and SMCCs when measured concentration is higher than 20% of the background level. In addition, experimental data demonstrated that two-step calibration strategy proposed here is a promising and reliable alternative strategy to quantify endogenous BAs in biological sample.PMID:37837894 | DOI:10.1016/j.jpba.2023.115785

Application of metabolomics in diagnostics and differentiation of meningitis: A narrative review with a critical approach to the literature

Sat, 14/10/2023 - 12:00
Biomed Pharmacother. 2023 Oct 12;168:115685. doi: 10.1016/j.biopha.2023.115685. Online ahead of print.ABSTRACTDue to its high mortality rate associated with various life-threatening sequelae, meningitis poses a vital problem in contemporary medicine. Numerous algorithms, many of which were derived with the aid of artificial intelligence, were brought up in a strive for perfection in predicting the status of sepsis-related survival or exacerbation. This review aims to provide key insights on the contextual utilization of metabolomics. The aim of this the metabolomic approach set of methods can be used to investigate both bacterial and host metabolite sets from both the host and its microbes in several types of specimens - even in one's breath, mainly with use of two methods - Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR). Metabolomics, and has been used to elucidate the mechanisms underlying disease development and metabolic identification changes in a wide range of metabolite contents, leading to improved methods of diagnosis, treatment, and prognosis of meningitis. Mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) are the main analytical platforms used in metabolomics. Its high sensitivity accounts for the usefulness of metabolomics in studies into meningitis, its sequelae, and concomitant comorbidities. Metabolomics approaches are a double-edged sword, due to not only their flexibility, but also - high complexity, as even minor changes in the multi-step methods can have a massive impact on the results. Information on the differential diagnosis of meningitis act as a background in presenting the merits and drawbacks of the use of metabolomics in context of meningeal infections.PMID:37837878 | DOI:10.1016/j.biopha.2023.115685

Multi-omics analysis reveals differential molecular responses to cadmium toxicity in rice root tip and mature zone

Sat, 14/10/2023 - 12:00
J Hazard Mater. 2023 Oct 11;462:132758. doi: 10.1016/j.jhazmat.2023.132758. Online ahead of print.ABSTRACTCadmium (Cd) is a highly toxic heavy metal that can be readily absorbed by plants and enriched in human body. Rice (Oryza sativa L.) yield and grain quality are affected by excessive Cd in the soil. Therefore, understanding the mechanisms of Cd absorption, accumulation and detoxification in the root apex is crucial for developing low-Cd rice cultivars. After Cd treatment, Cd concentration in rice root tips (RT) was 1.4 times higher than that in basal roots (BR). To uncover the distinct molecular responses to Cd toxicity, we conducted transcriptomic, proteomic, and metabolomic analyses on the two root sections. The results revealed that the RT exhibited 1.2-2.0 fold higher transcript or protein abundance of several Cd-related transporters than the BR, including Nramp1, Nramp5, IRT1, and HMA3, thereby contributing to more Cd accumulation in the RT. Furthermore, multi-omics analysis unveiled that the RT had enhanced activity in 'phenylpropanoid metabolism', 'AsA-GSH cycle' and 'tryptophan metabolism', conferring the stronger antioxidant system. While the BR showed higher activation in 'cell wall remodeling' and 'terpenoid biosynthesis'. This comprehensive study provides insights into the regulatory network of genes, proteins and metabolites involved in the differential responses to Cd toxicity between rice root tips and mature zones.PMID:37837773 | DOI:10.1016/j.jhazmat.2023.132758

Disturbed hippocampal histidine metabolism contributes to cognitive impairment induced by recurrent nonsevere hypoglycemia in diabetes

Sat, 14/10/2023 - 12:00
Biochem Biophys Res Commun. 2023 Oct 10;682:325-334. doi: 10.1016/j.bbrc.2023.10.036. Online ahead of print.ABSTRACTHypoglycemia is a common adverse reaction to glucose-lowering treatment. Diabetes mellitus (DM) combined with recurrent nonsevere hypoglycemia (RH) can accelerate cognitive decline. Currently, the metabolic pattern changes in cognition-related brain regions caused by this combined effect of DM and RH (DR) remain unclear. In this study, we first characterized the metabolic profiles of the hippocampus in mice exposed to DR using non-targeted metabolomic platforms. Our results showed that DR induced a unique metabolic pattern in the hippocampus, and several significant differences in metabolite levels belonging to the histidine metabolism pathway were discovered. Based on these findings, in the follow-up experiment, we found that histidine treatment could attenuate the cognitive impairment and rescue the neuronal and synaptic damage induced by DR in the hippocampus, which are closely related to ameliorated mitochondrial injury. These findings provide new insights into the metabolic mechanisms of the hippocampus in the progression of DR, and l-histidine supplementation may be a potential metabolic therapy in the future.PMID:37837753 | DOI:10.1016/j.bbrc.2023.10.036

Cadmium exposure dysregulates purine metabolism and homeostasis across the gut-liver axis in a mouse model

Sat, 14/10/2023 - 12:00
Ecotoxicol Environ Saf. 2023 Oct 12;266:115587. doi: 10.1016/j.ecoenv.2023.115587. Online ahead of print.ABSTRACTCadmium (Cd) exposure has been associated with the development of enterohepatic circulation disorders and hyperuricemia, but the possible contribution of chronic low-dose Cd exposure to disease progression is still need to be explored. A mouse model of wild-type mice (WT) and Uox-knockout mice (Uox-KO) to find out the toxic effects of chronic low-dose Cd exposure on liver purine metabolism by liquid chromatography-mass spectrometry (LC-MS) platform and associated intestinal flora. High throughput omics analysis including metabolomics and transcriptomics showed that Cd exposure can cause disruption of purine metabolism and energy metabolism. Cd changes several metabolites associated with purine metabolism (xanthine, hypoxanthine, adenosine, uridine, inosine) and related genes, which are associated with elevated urate levels. Microbiome analysis showed that Cd exposure altered the disturbance of homeostasis in the gut. Uox-KO mice were more susceptible to Cd than WT mice. Our findings extend the understanding of potential toxicological interactions between liver and gut microbiota and shed light on the progression of metabolic diseases caused by Cd exposure.PMID:37837700 | DOI:10.1016/j.ecoenv.2023.115587

Molecular mechanism of quality changes in solid endosperm of tender coconut during room temperature storage based on transcriptome and metabolome

Sat, 14/10/2023 - 12:00
Food Chem. 2023 Oct 6;436:137615. doi: 10.1016/j.foodchem.2023.137615. Online ahead of print.ABSTRACTTender coconut (TC) is popular around the world. Postharvest storage of TC leads to a decline in its appearance quality and flavor in both liquid endosperm (LE) and solid endosperm (SE). While LE is the most consumed part and remains in a liquid state, SE is the only cellular tissue directly connected to LE and may be the main contributor to flavor deterioration during storage. This study focused on investigating SE changes during TC storage at 25 °C using computed tomographic technology, transcriptome and metabolome analyses. The results showed increased thickness and density, elevated protein and fat contents, and decreased reducing and soluble sugars in SE of TC during storage. Integrated transcriptome and metabolome analysis revealed that these changes were mainly associated with the gene transcription levels involved in amino acid, carbohydrate and lipid metabolisms, along with specific metabolites. These findings offer valuable insights for controlling TC quality during storage.PMID:37837686 | DOI:10.1016/j.foodchem.2023.137615

Muscle growth affects the metabolome of the pectoralis major muscle in red-winged tinamou (Rhynchotus rufescens)

Sat, 14/10/2023 - 12:00
Poult Sci. 2023 Sep 12;102(12):103104. doi: 10.1016/j.psj.2023.103104. Online ahead of print.ABSTRACTThe aim of the present study was to identify and quantify the metabolites (metabolome analysis) of the pectoralis major muscle in male red-winged tinamou (Rhynchotus rufescens) selected for growth traits. A selection index was developed for females [body weight (BW), chest circumference (CC), and thigh circumference (TC)] and males [BW, CC, TC, semen volume, and sperm concentration] in order to divide the animals into 2 experimental groups: selection group with a higher index (TinamouS) and commercial group with a lower index (TinamouC). Twenty male offspring of the 2 groups (TinamouS, n = 10; TinamouC, n = 10) were confined for 350 d. The birds were slaughtered and pectoralis major muscle samples were collected, subjected to polar and apolar metabolites extractions and analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Analysis of the polar metabolomic profile identified 65 metabolites; 29 of them were differentially expressed between the experimental groups (P < 0.05). The TinamouS groups exhibited significantly higher concentrations (P < 0.05) of 25 metabolites, including anserine, aspartate, betaine, carnosine, creatine, glutamate, threonine, 3-methylhistidine, NAD+, pyruvate, and taurine. Significantly higher concentrations of cysteine, beta-alanine, lactose, and choline were observed in the TinamouC group (P < 0.05). The metabolites identified in the muscle provided information about the main metabolic pathways (higher impact value and P < 0.05), for example, phenylalanine, tyrosine and tryptophan biosynthesis; alanine, aspartate and glutamate metabolism; D-glutamine and D-glutamate metabolism; β-alanine metabolism; glycine, serine and threonine metabolism; taurine and hypotaurine metabolism; histidine metabolism; phenylalanine metabolism. The NMR spectra of apolar fraction showed 8 classes of chemical compounds. The metabolome analysis shows that the selection index resulted in the upregulation of polyunsaturated fatty acids, unsaturated fatty acids, phosphocholines, phosphoethanolamines, triacylglycerols, and glycerophospholipids. The present study suggests that, despite few generations, the selection based on muscle growth traits promoted changes in metabolite concentrations in red-winged tinamou.PMID:37837680 | DOI:10.1016/j.psj.2023.103104

Metabolites in aging and aging-relevant diseases: Frailty, sarcopenia and cognitive decline

Sat, 14/10/2023 - 12:00
Geriatr Gerontol Int. 2023 Oct 13. doi: 10.1111/ggi.14684. Online ahead of print.ABSTRACTAging shows biologically complex features with high individual variability, which reflects the exposure to several stimuli and the adaptation to them. Among them, metabolic changes are well observed as consequences or possible causes of aging. Calorie restriction extends organismal life span in experimental models. Several metabolites; for example, resveratrol or nicotinamide mononucleotide, are reported to mimic calorie restriction effects in vivo. Metabolomic research would be useful to evaluate metabolites as biomarkers in aging-relevant events and to identify metabolic regulation of aging. We recently developed the metabolomic approach for whole blood analysis, which functions as strong tool for this purpose. We review the update findings in aging-relevant metabolites detected by this method. Geriatr Gerontol Int 2023; ••: ••-••.PMID:37837183 | DOI:10.1111/ggi.14684

Effect of Chestnut (<em>Castanea Mollissima</em> Blume) Bur Polyphenol Extract on <em>Shigella dysenteriae</em>: Antibacterial Activity and the Mechanism

Sat, 14/10/2023 - 12:00
Molecules. 2023 Oct 9;28(19):6990. doi: 10.3390/molecules28196990.ABSTRACTShigella dysenteriae is a highly pathogenic microorganism that can cause human bacillary dysentery by contaminating food and drinking water. This study investigated the antibacterial activity of chestnut bur polyphenol extract (CBPE) on S. dysenteriae and the underlying mechanism. The results showed that the minimum inhibitory concentration (MIC) of CBPE for S. dysenteriae was 0.4 mg/mL, and the minimum bactericidal concentration (MBC) was 1.6 mg/mL. CBPE treatment irreversibly disrupted cell morphology, decreased cell activity, and increased cell membrane permeability, cell membrane depolarization, and cell content leakage of S. dysenteriae, indicating that CBPE has obvious destructive effects on the cell membrane and cell wall of S. dysenteriae. Combined transcriptomic and metabolomics analysis revealed that CBPE inhibits S. dysenteriae by interfering with ABC protein transport, sulfur metabolism, purine metabolism, amino acid metabolism, glycerophospholipid metabolism, and some other pathways. These findings provide a theoretical basis for the prevention and treatment of S. dysenteriae infection with extract from chestnut burs.PMID:37836834 | DOI:10.3390/molecules28196990

Shoot Cultures of <em>Vitis vinifera</em> (Vine Grape) Different Cultivars as a Promising Innovative Cosmetic Raw Material-Phytochemical Profiling, Antioxidant Potential, and Whitening Activity

Sat, 14/10/2023 - 12:00
Molecules. 2023 Sep 29;28(19):6868. doi: 10.3390/molecules28196868.ABSTRACTThe primary purpose of this work was the initiation and optimization of shoot cultures of different Vitis vinifera L. cultivars: cv. Chardonnay, cv. Hibernal, cv. Riesling, cv. Johanniter, cv. Solaris, cv. Cabernet Cortis, and cv. Regent. Cultures were maintained on 30-day growth cycles using two media, Murashige and Skoog (MS) and Schenk and Hildebrandt (SH), with various concentrations of plant growth regulators. Tested media ('W1'-'W4') contained varying concentrations of 6-benzylaminopurine (BA) in addition to indole-3-butyric acid (IBA) and 1-naphthaleneacetic acid (NAA). High performance liquid chromatography coupled with mass spectrometry (UPLC-MS) was used for metabolomic profiling. In all tested extracts, 45 compounds were identified (6 amino acids, 4 phenolic acids, 13 flavan-3-ols, 3 flavonols, and 19 stilbenoids). Principal component analysis (PCA) was performed to assess the influence of the genotype and medium on metabolic content. PCA showed that metabolic content was mainly influenced by genotype and to a lesser extent by medium composition. MS media variants induced the amino acid, procyanidin, and flavan-3-ol production. In addition, the antioxidant potential and anti-tyrosinase activity was measured spectrophotometrically. The studies on antioxidant activity clearly reveal very high efficiency in reducing free radicals in the tested extracts. The strongest tyrosinase inhibition capacity was proved for shoots cv. Hibernal cultured in SH medium and supplemented with NAA, with an inhibition of 17.50%. These studies show that in vitro cultures of V. vinifera cvs. can be proposed as an alternative source of plant material that can be potentially used in cosmetic industry.PMID:37836711 | DOI:10.3390/molecules28196868

Residue of Chlormequat and Regulatory Effects on the Specialized Metabolites of Astragali Radix

Sat, 14/10/2023 - 12:00
Molecules. 2023 Sep 22;28(19):6754. doi: 10.3390/molecules28196754.ABSTRACTPresently, the utilization of chlormequat in Astragalus mongholicus Bunge (Leguminosae) cultivation is prevalent for augmenting rhizome (Astragali Radix) yield. However, indiscriminate and excessive chlormequat employment can detrimentally influence Astragali Radix quality and safety. This research aimed to comprehensively comprehend chlormequat risks and its influence on Astragali Radix metabolites. Diverse chlormequat concentrations were employed in Astragalus mongholicus cultivation, with subsequent analysis of residual chlormequat levels in Astragali Radix across treatment groups. Astragali Radix metabolic profiling was conducted through UPLC-QTOF-MS, and thirteen principal active components were quantified via UFLC-MS/MS. Findings revealed a direct correlation between chlormequat residue levels in Astragali Radix and application concentration, with high-dose residue surpassing 5.0 mg/kg. Metabolomics analysis identified twenty-six distinct saponin and flavonoid metabolites. Notably, the application of chlormequat led to the upregulation of seven saponins (e.g., astragaloside I and II) and downregulation of six flavonoids (e.g., methylnissolin-3-O-glucoside and astraisoflavan-7-O-β-d-glucoside). Quantitative analysis demonstrated variable contents of active ingredients due to differing chlormequat concentrations, leading to astragaloside I increase (14.59-62.55%) and isoastragaloside II increase (4.8-55.63%), while methylnissolin-3-O-glucoside decreased (22.18-41.69%), as did astraisoflavan-7-O-β-d-glucoside (21.09-47.78%). In conclusion, chlormequat application influenced multiple active components in Astragali Radix, causing constituent proportion variations. Elevated chlormequat concentrations led to increased active components alongside heightened chlormequat residues in Astragali Radix. Consequently, prudent chlormequat application during Astragali Radix production is imperative to avert potential detriments to its quality and safety.PMID:37836597 | DOI:10.3390/molecules28196754

Nutrition, Metabolites, and Human Health

Sat, 14/10/2023 - 12:00
Nutrients. 2023 Oct 8;15(19):4286. doi: 10.3390/nu15194286.ABSTRACTThe field of metabolomics and related "omics" techniques allows for the identification of a vast array of molecules within biospecimens [...].PMID:37836568 | DOI:10.3390/nu15194286

The Southern European Atlantic Diet and Its Supplements: The Chemical Bases of Its Anticancer Properties

Sat, 14/10/2023 - 12:00
Nutrients. 2023 Oct 6;15(19):4274. doi: 10.3390/nu15194274.ABSTRACTScientific evidence increasingly supports the strong link between diet and health, acknowledging that a well-balanced diet plays a crucial role in preventing chronic diseases such as obesity, diabetes, cardiovascular issues, and certain types of cancer. This perspective opens the door to developing precision diets, particularly tailored for individuals at risk of developing cancer. It encompasses a vast research area and involves the study of an expanding array of compounds with multilevel "omics" compositions, including genomics, transcriptomics, proteomics, epigenomics, miRNomics, and metabolomics. We review here the components of the Southern European Atlantic Diet (SEAD) from both a chemical and pharmacological standpoint. The information sources consulted, complemented by crystallographic data from the Protein Data Bank, establish a direct link between the SEAD and its anticancer properties. The data collected strongly suggest that SEAD offers an exceptionally healthy profile, particularly due to the presence of beneficial biomolecules in its foods. The inclusion of olive oil and paprika in this diet provides numerous health benefits, and scientific evidence supports the anticancer properties of dietary supplements with biomolecules sourced from vegetables of the brassica genus. Nonetheless, further research is warranted in this field to gain deeper insights into the potential benefits of the SEAD's bioactive compounds against cancer.PMID:37836558 | DOI:10.3390/nu15194274

Differential Metabolites in Osteoarthritis: A Systematic Review and Meta-Analysis

Sat, 14/10/2023 - 12:00
Nutrients. 2023 Sep 28;15(19):4191. doi: 10.3390/nu15194191.ABSTRACT(1) Many studies have attempted to utilize metabolomic approaches to explore potential biomarkers for the early detection of osteoarthritis (OA), but consistent and high-level evidence is still lacking. In this study, we performed a systematic review and meta-analysis of differential small molecule metabolites between OA patients and healthy individuals to screen promising candidates from a large number of samples with the aim of informing future prospective studies. (2) Methods: We searched the EMBASE, the Cochrane Library, PubMed, Web of Science, Wan Fang Data, VIP Date, and CNKI up to 11 August 2022, and selected relevant records based on inclusion criteria. The risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. We performed qualitative synthesis by counting the frequencies of changing directions and conducted meta-analyses using the random effects model and the fixed-effects model to calculate the mean difference and 95% confidence interval. (3) Results: A total of 3798 records were identified and 13 studies with 495 participants were included. In the 13 studies, 132 kinds of small molecule differential metabolites were extracted, 58 increased, 57 decreased and 17 had direction conflicts. Among them, 37 metabolites appeared more than twice. The results of meta-analyses among four studies showed that three metabolites increased, and eight metabolites decreased compared to healthy controls (HC). (4) Conclusions: The main differential metabolites between OA and healthy subjects were amino acids (AAs) and their derivatives, including tryptophan, lysine, leucine, proline, phenylalanine, glutamine, dimethylglycine, citrulline, asparagine, acetylcarnitine and creatinine (muscle metabolic products), which could be potential biomarkers for predicting OA.PMID:37836475 | DOI:10.3390/nu15194191

Gut Microbiota Combined with Serum Metabolomics to Investigate the Hypoglycemic Effect of <em>Actinidia arguta</em> Leaves

Sat, 14/10/2023 - 12:00
Nutrients. 2023 Sep 23;15(19):4115. doi: 10.3390/nu15194115.ABSTRACTActinidia arguta leaves (AAL) are an excellent source of bioactive components for the food industry and possess many functional properties. However, the hypoglycemic effect and mechanism of AAL remain unclear. The aim of this work was to investigate the potential hypoglycemic effect of AAL and explore its possible mechanism using 16S rRNA sequencing and serum metabolomics in diabetic mice induced by high-fat feeding in combination with streptozotocin injection. A total of 25 flavonoids from AAL were isolated and characterized, and the contents of the extract from the AAL ranged from 0.14 mg/g DW to 8.97 mg/g DW. The compound quercetin (2) had the highest content of 8.97 ± 0.09 mg/g DW, and the compound kaempferol-3-O-(2'-O-D-glucopyl)-β-D-rutinoside (12) had the lowest content of 0.14 ± 0.01 mg/g DW. In vivo experimental studies showed that AAL reduced blood glucose and cholesterol levels, improved insulin sensitivity, and ameliorated oxidative stress and liver and kidney pathological damage. In addition, gut microbiota analysis found that AAL significantly reduced the F/B ratio, enriched the beneficial bacteria Bacteroides and Bifidobacterium, and inhibited the harmful bacteria Lactobacillus and Desulfovibrio, thereby playing an active role in intestinal imbalance. In addition, metabolomics analysis showed that AAL could improve amino acid metabolism and arachidonic acid metabolism, thereby exerting a hypoglycemic effect. This study confirmed that AAL can alleviate type 2 diabetes mellitus (T2DM) by regulating intestinal flora and interfering with related metabolic pathways, providing a scientific basis for its use as a dietary supplement and for further exploration of the mechanism of AAL against T2DM.PMID:37836402 | DOI:10.3390/nu15194115

Comparative Transcriptome and Metabolome Profiling Reveal Mechanisms of Red Leaf Color Fading in <em>Populus</em> × <em>euramericana</em> cv. 'Zhonghuahongye'

Sat, 14/10/2023 - 12:00
Plants (Basel). 2023 Oct 9;12(19):3511. doi: 10.3390/plants12193511.ABSTRACTAnthocyanins are among the flavonoids that serve as the principal pigments affecting the color of plants. During leaf growth, the leaf color of 'Zhonghuahongye' gradually changes from copper-brown to yellow-green. At present, the mechanism of color change at different stages has not yet been discovered. To find this, we compared the color phenotype, metabolome, and transcriptome of the three leaf stages. The results showed that the anthocyanin content of leaves decreased by 62.5% and the chlorophyll content increased by 204.35%, 69.23%, 155.56% and 60%, respectively. Differential metabolites and genes were enriched in the pathway related to the synthesis of 'Zhonghuahongye' flavonoids and anthocyanins and to the biosynthesis of secondary metabolites. Furthermore, 273 flavonoid metabolites were detected, with a total of eight classes. DFR, FLS and ANS downstream of anthocyanin synthesis may be the key structural genes in reducing anthocyanin synthesis and accumulation in the green leaf of 'Zhonghuahongye'. The results of multi-omics analysis showed that the formation of color was primarily affected by anthocyanin regulation and its related synthesis-affected genes. This study preliminarily analyzed the green regression gene and metabolic changes in 'Zhonghuahongye' red leaves and constitutes a reference for the molecular breeding of 'Zhonghuahongye' red leaves.PMID:37836251 | DOI:10.3390/plants12193511

Transcriptome and Metabolome Provide Insights into Fruit Ripening of Cherry Tomato (<em>Solanum lycopersicum</em> var. <em>cerasiforme</em>)

Sat, 14/10/2023 - 12:00
Plants (Basel). 2023 Oct 9;12(19):3505. doi: 10.3390/plants12193505.ABSTRACTInsights into flavor formation during fruit ripening can guide the development of breeding strategies that balance consumer and producer needs. Cherry tomatoes possess a distinctive taste, yet research on quality formation is limited. Here, metabolomic and transcriptomic analyses were conducted on different ripening stages. The results revealed differentially accumulated metabolites during fruit ripening, providing candidate metabolites related to flavor. Interestingly, several key flavor-related metabolites already reached a steady level at the mature green stage. Transcriptomic analysis revealed that the expression levels of the majority of genes tended to stabilize after the pink stage. Enrichment analysis demonstrated that changes in metabolic and biosynthetic pathways were evident throughout the entire process of fruit ripening. Compared to disease resistance and fruit color genes, genes related to flavor and firmness may have a broader impact on the accumulation of metabolites. Furthermore, we discovered the interconversion patterns between glutamic acid and glutamine, as well as the biosynthesis patterns of flavonoids. These findings contribute to our understanding of fruit quality formation mechanisms and support breeding programs aimed at improving fruit quality traits.PMID:37836245 | DOI:10.3390/plants12193505

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