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

Unique Metabolic Profiles Associate with Gestational Diabetes and Ethnicity in Low- and High-Risk Women Living in the UK

Sat, 11/02/2023 - 12:00
J Nutr. 2022 Oct;152(10):2186-2197. doi: 10.1093/jn/nxac163.ABSTRACTBACKGROUND: Gestational diabetes mellitus (GDM) is the most common global pregnancy complication; however, prevalence varies substantially between ethnicities, with South Asians (SAs) experiencing up to 3 times the risk of the disease compared with white Europeans (WEs). Factors driving this discrepancy are unclear, although the metabolome is of great interest as GDM is known to be characterized by metabolic dysregulation.OBJECTIVES: The primary aim was to characterize and compare the metabolic profiles of GDM in SA and WE women (at <28 wk of gestation) from the Born in Bradford (BIB) prospective birth cohort in the United Kingdom.METHODS: In total, 146 fasting serum metabolites, from 2,668 pregnant WE and 2,671 pregnant SA women (average BMI 26.2 kg/m2, average age 27.3 y) were analyzed using partial least squares discriminatory analyses to characterize GDM status. Linear associations between metabolite values and post-oral glucose tolerance test measures of dysglycemia (fasting glucose and 2 h postglucose) were also examined.RESULTS: Seven metabolites associated with GDM status in both ethnicities (variable importance in projection ≥1), whereas 6 additional metabolites associated with GDM only in WE women. Unique metabolic profiles were observed in healthy-weight women who later developed GDM, with distinct metabolite patterns identified by ethnicity and BMI status. Of the metabolite values analyzed in relation to dysglycemia, lactate, histidine, apolipoprotein A1, HDL cholesterol, and HDL2 cholesterol associated with decreased glucose concentration, whereas DHA and the diameter of very low-density lipoprotein particles (nm) associated with increased glucose concertation in WE women, and in SAs, albumin alone associated with decreased glucose concentration.CONCLUSIONS: This study shows that the metabolic risk profile for GDM differs between WE and SA women enrolled in BiB in the United Kingdom. This suggests that etiology of the disease differs between ethnic groups and that ethnic-appropriate prevention strategies may be beneficial.PMID:36774176 | DOI:10.1093/jn/nxac163

Diet Patterns Are Associated with Circulating Metabolites and Lipid Profiles of South Asians in the United States

Sat, 11/02/2023 - 12:00
J Nutr. 2022 Nov;152(11):2358-2366. doi: 10.1093/jn/nxac191.ABSTRACTBACKGROUND: South Asians are at higher risk for cardiometabolic disease than many other racial/ethnic minority groups. Diet patterns in US South Asians have unique components associated with cardiometabolic disease.OBJECTIVES: We aimed to characterize the metabolites associated with 3 representative diet patterns.METHODS: We included 722 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40-84 y without known cardiovascular disease. Fasting serum specimens and diet and demographic questionnaires were collected at baseline and diet patterns previously generated through principal components analysis. LC-MS-based untargeted metabolomic and lipidomic analysis was conducted with targeted integration of known metabolite and lipid signals. Linear regression models of diet pattern factor score and log-transformed metabolites adjusted for age, sex, caloric intake, and BMI and adjusted for multiple comparisons were performed, followed by elastic net linear regression of significant metabolites.RESULTS: There were 443 metabolites of known identity extracted from the profiling data. The "animal protein" diet pattern was associated with 61 metabolites and lipids, including glycerophospholipids phosphatidylethanolamine PE(O-16:1/20:4) and/or PE(P-16:0/20:4) (β: 0.13; 95% CI: 0.11, 0.14) and N-acyl phosphatidylethanolamines (NAPEs) NAPE(O-18:1/20:4/18:0) and/or NAPE(P-18:0/20:4/18:0) (β: 0.13; 95% CI: 0.11, 0.14), lysophosphatidylinositol (LPI) (22:6/0:0) (β: 0.14; 95% CI: 0.12, 0.17), and fatty acid (FA) (22:6) (β: 0.15; 95% CI: 0.13, 0.17). The "fried snacks, sweets, high-fat dairy" pattern was associated with 12 lipids, including PC(16:0/22:6) (β: -0.08; 95% CI: -0.09, -0.06) and FA (22:6) (β: 0.14; 95% CI: -0.17, -0.10). The "fruits, vegetables, nuts, and legumes" pattern was associated with 5 metabolites including proline betaine (β: 0.17; 95% CI: 0.09, 0.25) (P < 0.0002).CONCLUSIONS: Three predominant dietary patterns in US South Asians are associated with circulating metabolites differentiated by lipids including glycerophospholipids and PUFAs and the amino acid proline betaine.PMID:36774102 | DOI:10.1093/jn/nxac191

The Fecal Metabolome Links Diet Composition, Foacidic positive ion conditions, chromatographicallyod Processing, and the Gut Microbiota to Gastrointestinal Health in a Randomized Trial of Adults Consuming a Processed Diet

Sat, 11/02/2023 - 12:00
J Nutr. 2022 Nov;152(11):2343-2357. doi: 10.1093/jn/nxac161.ABSTRACTBACKGROUND: Food processing alters diet digestibility and composition, thereby influencing interactions between host biology, diet, and the gut microbiota. The fecal metabolome offers insight into those relations by providing a readout of diet-microbiota interactions impacting host health.OBJECTIVES: The aims were to determine the effects of consuming a processed diet on the fecal metabolome and to explore relations between changes in the fecal metabolome with fecal microbiota composition and gastrointestinal health markers.METHODS: This was a secondary analysis of a randomized controlled trial wherein healthy adults [94% male; 18-61 y; BMI (kg/m2): 26 ± 3] consumed their usual diet [control (CON), n = 27] or a Meal, Ready-to-EatTM (Ameriqual Packaging) military ration diet composed of processed, shelf-stable, ready-to-eat items for 21 d (MRE; n = 27). Fecal metabolite profiles, fecal microbiota composition, biomarkers of intestinal barrier function, and gastrointestinal symptoms were measured before and after the intervention. Between-group differences and associations were assessed using nonparametric t tests, partial least-squares discriminant analysis, correlation, and redundancy analysis.RESULTS: Fecal concentrations of multiple dipeptides [Mann-Whitney effect size (ES) = 0.27-0.50] and long-chain SFAs (ES = 0.35-0.58) increased, whereas plant-derived compounds (ES = 0.31-0.60) decreased in MRE versus CON (P < 0.05; q < 0.20). Changes in dipeptides correlated positively with changes in fecal concentrations of Maillard-reaction products (ρ = 0.29-0.70; P < 0.05) and inversely with changes in serum prealbumin (ρ = -0.30 to -0.48; P ≤ 0.03). Multiple bile acids, coffee and caffeine metabolites, and plant-derived compounds were associated with both fecal microbiota composition and gastrointestinal health markers, with changes in fecal microbiota composition explaining 26% of the variability within changes in gastrointestinal health-associated fecal metabolites (P = 0.001).CONCLUSIONS: Changes in the fecal metabolomes of adults consuming a Meal, Ready-to-EatTM diet implicate interactions between diet composition, diet digestibility, and the gut microbiota as contributing to variability within gastrointestinal responses to the diet. Findings underscore the need to consider both food processing and nutrient composition when investigating the impact of diet-gut microbiota interactions on health outcomes. This trial was registered at www.CLINICALTRIALS: gov as NCT02423551.PMID:36774101 | DOI:10.1093/jn/nxac161

Machine Learning in Nutrition Research

Sat, 11/02/2023 - 12:00
Adv Nutr. 2022 Nov;13(6):2573-2589. doi: 10.1093/advances/nmac103.ABSTRACTData currently generated in the field of nutrition are becoming increasingly complex and high-dimensional, bringing with them new methods of data analysis. The characteristics of machine learning (ML) make it suitable for such analysis and thus lend itself as an alternative tool to deal with data of this nature. ML has already been applied in important problem areas in nutrition, such as obesity, metabolic health, and malnutrition. Despite this, experts in nutrition are often without an understanding of ML, which limits its application and therefore potential to solve currently open questions. The current article aims to bridge this knowledge gap by supplying nutrition researchers with a resource to facilitate the use of ML in their research. ML is first explained and distinguished from existing solutions, with key examples of applications in the nutrition literature provided. Two case studies of domains in which ML is particularly applicable, precision nutrition and metabolomics, are then presented. Finally, a framework is outlined to guide interested researchers in integrating ML into their work. By acting as a resource to which researchers can refer, we hope to support the integration of ML in the field of nutrition to facilitate modern research.PMID:36774043 | DOI:10.1093/advances/nmac103

Prediction of hospitalisations based on wastewater-based SARS-CoV-2 epidemiology

Sat, 11/02/2023 - 12:00
Sci Total Environ. 2023 Feb 9:162149. doi: 10.1016/j.scitotenv.2023.162149. Online ahead of print.ABSTRACTWastewater-based epidemiology is widely applied in Austria since April 2020 to monitor the SARS-CoV-2 pandemic. With a steadily increasing number of monitored wastewater facilities, 123 plants covering roughly 70 % of the 9 million population were monitored as of August 2022. In this study, the SARS-CoV-2 viral concentrations in raw sewage were analysed to infer short-term hospitalisation occupancy. The temporal lead of wastewater-based epidemiological time series over hospitalisation occupancy levels facilitates the construction of forecast models. Data pre-processing techniques are presented, including the approach of comparing multiple decentralised wastewater signals with aggregated and centralised clinical data. Time‑lead quantification was performed using cross-correlation analysis and coefficient of determination optimisation approaches. Multivariate regression models were successfully applied to infer hospitalisation bed occupancy. The results show a predictive potential of viral loads in sewage towards Covid-19 hospitalisation occupancy, with an average lead time towards ICU and non-ICU bed occupancy between 14.8-17.7 days and 8.6-11.6 days, respectively. The presented procedure provides access to the trend and tipping point behaviour of pandemic dynamics and allows the prediction of short-term demand for public health services. The results showed an increase in forecast accuracy with an increase in the number of monitored wastewater treatment plants. Trained models are sensitive to changing variant types and require recalibration of model parameters, likely caused by immunity by vaccination and/or infection. The utilised approach displays a practical and rapidly implementable application of wastewater-based epidemiology to infer hospitalisation occupancy.PMID:36773921 | DOI:10.1016/j.scitotenv.2023.162149

Cellular transformation promotes the incorporation of docosahexaenoic acid into the endolysosome-specific lipid bis(monoacylglycerol)phosphate in breast cancer

Sat, 11/02/2023 - 12:00
Cancer Lett. 2023 Feb 9:216090. doi: 10.1016/j.canlet.2023.216090. Online ahead of print.ABSTRACTBis(monoacylglycero)phosphates (BMPs), a class of lipids highly enriched within endolysosomal organelles, are key components of the lysosomal intraluminal vesicles responsible for activating sphingolipid catabolic enzymes. While BMPs are understudied relative to other phospholipids, recent reports associate BMP dysregulation with a variety of pathological states including neurodegenerative diseases and lysosomal storage disorders. Since the dramatic lysosomal remodeling characteristic of cellular transformation could impact BMP abundance and function, we employed untargeted lipidomics approaches to identify and quantify BMP species in several in vitro and in vivo models of breast cancer and comparative non-transformed cells and tissues. We observed lower BMP levels within transformed cells relative to normal cells, and consistent enrichment of docosahexaenoic acid (22:6) fatty acyl chain-containing BMP species in both human- and mouse-derived mammary tumorigenesis models. Our functional analysis points to a working model whereby 22:6 BMPs serve as reactive oxygen species scavengers in tumor cells, protecting lysosomes from oxidant-induced lysosomal membrane permeabilization. Our findings suggest that breast tumor cells might divert polyunsaturated fatty acids into BMP lipids as part of an adaptive response to protect their lysosomes from elevated reactive oxygen species levels, and raise the possibility that BMP-mediated lysosomal protection is a tumor-specific vulnerability that may be exploited therapeutically.PMID:36773796 | DOI:10.1016/j.canlet.2023.216090

Harnessing the omics revolution to address the global biodiversity crisis

Sat, 11/02/2023 - 12:00
Curr Opin Biotechnol. 2023 Feb 9;80:102901. doi: 10.1016/j.copbio.2023.102901. Online ahead of print.ABSTRACTHuman disturbances are altering global biodiversity in unprecedented ways. We identify three fundamental challenges underpinning our understanding of global biodiversity (namely discovery, loss, and preservation), and discuss how the omics revolution (e.g. genomics, transcriptomics, proteomics, metabolomics, and meta-omics) can help address these challenges. We also discuss how omics tools can illuminate the major drivers of biodiversity loss, including invasive species, pollution, urbanization, overexploitation, and climate change, with a special focus on highly diverse tropical environments. Although omics tools are transforming the traditional toolkit of biodiversity research, their application to addressing the current biodiversity crisis remains limited and may not suffice to offset current rates of biodiversity loss. Despite technical and logistical challenges, omics tools need to be fully integrated into global biodiversity research, and better strategies are needed to improve their translation into biodiversity policy and practice. It is also important to recognize that although the omics revolution can be considered the biologist's dream, socioeconomic disparity limits their application in biodiversity research.PMID:36773576 | DOI:10.1016/j.copbio.2023.102901

A novel mechanism of Dimethyl ester of Alpha-ketoglutarate in suppressing Paraquat-induced BEAS-2B cell injury by alleviating GSDME dependent pyroptosis

Sat, 11/02/2023 - 12:00
Phytomedicine. 2023 Feb 5;112:154698. doi: 10.1016/j.phymed.2023.154698. Online ahead of print.ABSTRACTBACKGROUND: Acute lung injury (ALI) induced by paraquat (PQ) progresses rapidly, leading to high mortality; however, there is no specific antidote. Our limited knowledge of the pathogenic toxicological mechanisms of PQ has hindered the development of treatments against PQ exposure.PURPOSE: Pyroptosis is a form of programmed cell death recently identified as a novel molecular mechanism adopted by chemotherapeutic drugs for cancer therapy. However, the involvement of pyroptosis in PQ-induced lung injury has not been reported. Therefore, we investigated the effects of PQ on the lung tissues to elucidate the molecular mechanisms underlying its toxicity, especially its ability to induce pyroptosis.METHODS: To observe the morphological changes of BEAS-2B cells exposed to PQ, the plasma membrane damage of the cells was detected by LDH release assay, mitochondrial function and cell metabolism were detected by energy metabolism analysis. Western blotting was used to detect the protein levels of GSDMD, C-GSDMD, GSDME and N-GSDME in BEAS-2B cells. Metabolites of TCA cycle were detected by metabolomics, and the changes of TCA cycle metabolic enzymes in cells were detected by Western blotting.RESULTS: We observed that PQ induced proteolytic cleavage of gasdermin E (GSDME) with concomitant cleavage of caspase 3 in BEAS-2B cells. Knockout of GSDME attenuated PQ-induced cell death. Additionally, PQ induced ROS accumulation, mitochondrial depolarisation, and mitochondrial dysfunction in these cells. PQ activated the caspase 3/GSDME pathway and damaged the cytoplasmic membrane in cells, leading to pyroptosis. We demonstrated that DMK suppressed PQ-induced pyroptosis by blocking PQ-induced caspase 3/GSDME pathway activation, reducing cellular ROS levels, and improving mitochondrial function.CONCLUSION: These findings provide novel insights into the previously unrecognized mechanism of GSDME-dependent pyroptosis in PQ poisoning.PMID:36773430 | DOI:10.1016/j.phymed.2023.154698

Over-the-counter fish oil supplementation and pro-resolving and pro-inflammatory lipid mediators in rheumatoid arthritis

Sat, 11/02/2023 - 12:00
Prostaglandins Leukot Essent Fatty Acids. 2023 Jan 26;190:102542. doi: 10.1016/j.plefa.2023.102542. Online ahead of print.ABSTRACTOBJECTIVE: Little is known about the effects of over-the-counter fish oil (FO) supplements on circulating omega-3 polyunsaturated fatty acid (n-3 PUFA)-derived specialized pro-resolving mediators (SPMs), nor about whether having a chronic inflammatory disease such as rheumatoid arthritis (RA) influences SPM levels. We investigated associations between over-the-counter n-3 PUFA FO supplementation and circulating SPMs among patients with vs. without RA.METHODS: We studied 104 participants: 26 with RA taking FO matched by age and sex to 26 with RA not taking FO, 26 without RA taking FO, and 26 without RA not taking FO. Targeted-liquid chromatography-tandem mass spectroscopy was performed on patient plasma to identify and quantify 27 lipid mediators (including eicosanoids and SPMs). We performed t-tests and then multivariable linear regression analyses to assess whether having RA or taking FO supplements was associated with circulating lipid mediator concentrations, adjusting for age, race, sex, smoking, body mass index, and current medication use (statins, prednisone and immunomodulators among RA cases only). We tested for interactions between FO supplementation and RA status. We also conducted Spearman's correlations between EPA, DHA, and ARA and their downstream metabolites.RESULTS: Among patients who were taking FO compared to those who were not, in multivariable- adjusted analyses, SPM substrates EPA and DHA were both elevated as were several of their pro-resolving bioactive products, including 15- and 18-HEPE from EPA, and 14- and 17-HDHA from DHA, which are substrates for specific SPMs. While E-series and D-series resolvins were present and identified, we did not find statistical elevations of other SPMs. Results were similar among patients with RA and patients without RA, taking vs. not taking FO supplementation (no formal statistical interaction observed). There was a strong positive correlation between EPA and DHA and their immediate downstream SPM precursors (18-HEPE and15-HEPE from EPA; 17-HDHA and 14-HDHA from DHA) among all patients.CONCLUSION: Patients taking FO supplements, regardless of RA status, not only had higher blood levels of EPA and DHA, but also of their enzymatic products 18-HEPE (E-series resolvin precursors), 15-HEPE and 17-HDHA (D-series resolvin and protectin precursors). Patients with RA, an inflammatory autoimmune disease, may be able to augment some SPM precursor reserves, similarly to matched controls without RA, by taking oral FO supplements.PMID:36773395 | DOI:10.1016/j.plefa.2023.102542

Altered transcriptomic and metabolomic profiles of testicular interstitial fluid during aging in mice

Sat, 11/02/2023 - 12:00
Theriogenology. 2023 Feb 5;200:86-95. doi: 10.1016/j.theriogenology.2023.02.004. Online ahead of print.ABSTRACTThe testicular interstitial fluid (TIF) that bathes seminiferous tubules and testicular interstitial cells is the main microenvironment of the testis and involved in crosstalk between testicular cells. TIF also provides a new mean to investigate dysfunctional states of testis such as spermatogenic disorder and aging. In this study, we performed integrative omics analysis on the exosomal transcriptomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS) based non-targeted metabolomics in TIF by comparison between 21-month-old and 3-month-old male mice. A total of 1627 genes were identified as aging-related differently expressed genes (DEGs) in mouse TIF exosomes, with 1139 downregulated and 488 upregulated. Functional and pathway analysis revealed that the DEGs were associated with oxidative stress, carbon metabolism, and systemic lupus erythematosus. By comparing the DEGs with the Aging Atlas Database, we screened out key aging-related genes functioning as oxidative stress regulators, and their expression pattern in human testis with age was confirmed by immunohistochemistry results in the Human Protein Atlas database. In addition, the metabolomic analysis identified mild differences between young and old groups with 28 downregulated differently expressed metabolites (DEMs) and 6 upregulated DEMs, in the negative ion mode, including decreased level of several antioxidant metabolites. The KEGG analysis demonstrated that 10 pathways were upregulated, while the pyrimidine metabolism pathway was downregulated in the aged mice TIF. Taken together, this study highlighted the prominent role of oxidative stress that contributed to the aging microenvironment in the TIF, and brought comprehensive transcriptomic and metabolomic perspectives for understanding the mechanism underlying the testicular aging.PMID:36773384 | DOI:10.1016/j.theriogenology.2023.02.004

Exploration of fMRI brain responses to oral sucrose after Roux-en-Y gastric bypass in obese yucatan minipigs in relationship with microbiota and metabolomics profiles

Sat, 11/02/2023 - 12:00
Clin Nutr. 2023 Feb 2;42(3):394-410. doi: 10.1016/j.clnu.2023.01.015. Online ahead of print.ABSTRACTBACKGROUND & AIMS: In most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut-brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control.METHODS: An integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis.RESULTS: We showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP.CONCLUSION: This longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.PMID:36773369 | DOI:10.1016/j.clnu.2023.01.015

DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development

Sat, 11/02/2023 - 12:00
Cell Rep. 2023 Feb 10;42(2):112106. doi: 10.1016/j.celrep.2023.112106. Online ahead of print.ABSTRACTDrak2-deficient (Drak2-/-) mice are resistant to multiple models of autoimmunity yet effectively eliminate pathogens and tumors. Thus, DRAK2 represents a potential target to treat autoimmune diseases. However, the mechanisms by which DRAK2 contributes to autoimmunity, particularly type 1 diabetes (T1D), remain unresolved. Here, we demonstrate that resistance to T1D in non-obese diabetic (NOD) mice is due to the absence of Drak2 in T cells and requires the presence of regulatory T cells (Tregs). Contrary to previous hypotheses, we show that DRAK2 does not limit TCR signaling. Rather, DRAK2 regulates IL-2 signaling by inhibiting STAT5A phosphorylation. We further demonstrate that enhanced sensitivity to IL-2 in the absence of Drak2 augments thymic Treg development. Overall, our data indicate that DRAK2 contributes to autoimmunity in multiple ways by regulating thymic Treg development and by impacting the sensitivity of conventional T cells to Treg-mediated suppression.PMID:36773294 | DOI:10.1016/j.celrep.2023.112106

Prospects of emerging PAH sources and remediation technologies: insights from Africa

Sat, 11/02/2023 - 12:00
Environ Sci Pollut Res Int. 2023 Feb 11. doi: 10.1007/s11356-023-25833-9. Online ahead of print.ABSTRACTRemediation of polluted environmental media is critical to realization of the goals of the United Nations Decade on Ecosystem Restoration (UNDER) project. Many natural-resource dependent economies in Africa are characterized by numerous contaminated sites resulting from conventional and artisanal natural-resource mining. Alongside these extractive activities, there are refining, processing, and power plant operations, agriculture, urban, and infrastructure developments that contribute to increased discharges of toxins into the environment, particularly polycyclic aromatic hydrocarbons (PAHs), which are carcinogenic in nature. As a result, human and environmental receptors (i.e., air, water, soil, and biota) face increasing risk of exposure to higher concentrations of PAH. Evidence exists of widespread PAH contamination and in some instances where corrective action has been taken, residual contaminant levels exceeding regulatory thresholds remain in the environment due to the use of inappropriate and unsustainable remedial methods. Considering the long-term harmful effects of PAH on human and ecosystem health, land use, and the complexity of Africa's environmental deterioration, it is essential to explore remediation strategies that benefit both the environment and the economy. This review examined the status, opportunities, and challenges related to the application of emerging green technologies to remediate PAH-contaminated sites in five African countries (South Africa, Nigeria, Angola, Egypt, and Kenya). This paper concludes that bioremediation presents a sustainable option, considering its low net emissions and environmental footprints, and its low economic cost to Africa's poor communities and overburdened economy. However, an integration of biological and physico-chemical approaches could address various compounds and concentrations of PAH contamination.PMID:36773255 | DOI:10.1007/s11356-023-25833-9

Increased fatty acid metabolism and decreased glycolysis are hallmarks of metabolic reprogramming within microglia in degenerating white matter during recovery from experimental stroke

Sat, 11/02/2023 - 12:00
J Cereb Blood Flow Metab. 2023 Feb 11:271678X231157298. doi: 10.1177/0271678X231157298. Online ahead of print.ABSTRACTThe goal of this study was to evaluate changes in metabolic homeostasis during the first 12 weeks of recovery in a distal middle cerebral artery occlusion mouse model of stroke. To achieve this goal, we compared the brain metabolomes of ipsilateral and contralateral hemispheres from aged male mice up to 12 weeks after stroke to that of age-matched naïve and sham mice. There were 707 biochemicals detected in each sample by liquid chromatography-mass spectroscopy (LC-MS). Mitochondrial fatty acid β-oxidation, indicated by acyl carnitine levels, was increased in stroked tissue at 1 day and 4 weeks following stroke. Glucose and several glycolytic intermediates were elevated in the ipsilateral hemisphere for 12 weeks compared to the aged naïve controls, but pyruvate was decreased. Additionally, itaconate, a glycolysis inhibitor associated with activation of anti-inflammatory mechanisms in myeloid cells, was higher in the same comparisons. Spatial transcriptomics and RNA in situ hybridization localized these alterations to microglia within the area of axonal degeneration. These results indicate that chronic metabolic differences exist between stroked and control brains, including alterations in fatty acid metabolism and glycolysis within microglia in areas of degenerating white matter for at least 12 weeks after stroke.PMID:36772984 | DOI:10.1177/0271678X231157298

Gene Profiling of the Ascorbate Oxidase Family Genes under Osmotic and Cold Stress Reveals the Role of AnAO5 in Cold Adaptation in <em>Ammopiptanthus nanus</em>

Sat, 11/02/2023 - 12:00
Plants (Basel). 2023 Feb 3;12(3):677. doi: 10.3390/plants12030677.ABSTRACTThe uplift of the Qinghai Tibet Plateau has led to a drastic change in the climate in Central Asia, from warm and rainy, to dry and less rainfall. Ammopiptanthus nanus, a rare evergreen broad-leaved shrub distributed in the temperate desert region of Central Asia, has survived the drastic climate change in Central Asia caused by the uplift of the Qinghai-Tibet Plateau. Ascorbate oxidase (AO) regulates the redox status of the apoplast by catalyzing the oxidation of ascorbate acid to dehydroascorbic acid, and plays a key role in the adaptation of plants to environmental changes. Analyzing the evolution, environmental response, and biological functions of the AO family of A. nanus is helpful for understanding how plant genome evolution responds to climate change in Central Asia. A total of 16 AOs were identified in A. nanus, all of which contained the ascorbate oxidase domain, most of which contained transmembrane domain, and many were predicted to be localized in the apoplast. Segmental duplication and tandem duplication are the main factors driving the gene amplification of the AO gene family in A. nanus. Gene expression analysis based on transcriptome data and fluorescence quantitative PCR, as well as enzyme activity measurements, showed that the expression levels of AO genes and total enzyme activity decreased under short-term osmotic stress and low-temperature stress, but the expression of some AO genes (AnAO5, AnAO13, and AnAO16) and total enzyme activity increased under 7 days of cold stress. AnAO5 and AnAO11 are targeted by miR4415. Further functional studies on AnAO5 showed that AnAO5 protein was localized in the apoplast. The expression of AnAO5 in yeast cells and the transient expression in tobacco enhanced the tolerance of yeast and tobacco to low-temperature stress, and the overexpression of AnAO5 enhanced the tolerance of Arabidopsis seedlings to cold stress. Our research provides important data for understanding the role of AOs in plant adaptation to environmental change.PMID:36771760 | DOI:10.3390/plants12030677

Untargeted Metabolomics Analysis of the Orchid Species <em>Oncidium sotoanum</em> Reveals the Presence of Rare Bioactive C-Diglycosylated Chrysin Derivatives

Sat, 11/02/2023 - 12:00
Plants (Basel). 2023 Feb 2;12(3):655. doi: 10.3390/plants12030655.ABSTRACTPlants are valuable sources of secondary metabolites with pharmaceutical properties, but only a small proportion of plant life has been actively exploited for medicinal purposes to date. Underexplored plant species are therefore likely to contain novel bioactive compounds. In this study, we investigated the content of secondary metabolites in the flowers, leaves and pseudobulbs of the orchid Oncidium sotoanum using an untargeted metabolomics approach. We observed the strong accumulation of C-diglycosylated chrysin derivatives, which are rarely found in nature. Further characterization revealed evidence of antioxidant activity (FRAP and DPPH assays) and potential activity against neurodegenerative disorders (MAO-B inhibition assay) depending on the specific molecular structure of the metabolites. Natural product bioprospecting in underexplored plant species based on untargeted metabolomics can therefore help to identify novel chemical structures with diverse pharmaceutical properties.PMID:36771739 | DOI:10.3390/plants12030655

Host Tree and Geography Induce Metabolic Shifts in the Epiphytic Liverwort <em>Radula complanata</em>

Sat, 11/02/2023 - 12:00
Plants (Basel). 2023 Jan 27;12(3):571. doi: 10.3390/plants12030571.ABSTRACTBryophytes are prolific producers of unique, specialized metabolites that are not found in other plants. As many of these unique natural products are potentially interesting, for example, pharmacological use, variations in the production regarding ecological or environmental conditions have not often been investigated. Here, we investigate metabolic shifts in the epiphytic Radula complanata L. (Dumort) with regard to different environmental conditions and the type of phorophyte (host tree). Plant material was harvested from three different locations in Sweden, Germany, and Canada and subjected to untargeted liquid chromatography high-resolution mass-spectrometry (UPLC/ESI-QTOF-MS) and data-dependent acquisition (DDA-MS). Using multivariate statistics, variable selection methods, in silico compound identification, and compound classification, a large amount of variation (39%) in the metabolite profiles was attributed to the type of host tree and 25% to differences in environmental conditions. We identified 55 compounds to vary significantly depending on the host tree (36 on the family level) and 23 compounds to characterize R. complanata in different environments. Taken together, we found metabolic shifts mainly in primary metabolites that were associated with the drought response to different humidity levels. The metabolic shifts were highly specific to the host tree, including mostly specialized metabolites suggesting high levels of ecological interaction. As R. complanata is a widely distributed generalist species, we found it to flexibly adapt its metabolome according to different conditions. We found metabolic composition to also mirror the constitution of the habitat, which makes it interesting for conservation measures.PMID:36771656 | DOI:10.3390/plants12030571

Metabolomics and Transcriptomics Provide Insights into Lipid Biosynthesis in the Embryos of Walnut (<em>Juglans regia</em> L.)

Sat, 11/02/2023 - 12:00
Plants (Basel). 2023 Jan 24;12(3):538. doi: 10.3390/plants12030538.ABSTRACTWalnut (Juglans regia L.) is an important woody oilseed tree species due to its commercial value. However, the regulation mechanism of walnut oil accumulation is still poorly understood, which restricted the breeding and genetic improvement of high-quality oil-bearing walnuts. In order to explore the metabolic mechanism that regulates the synthesis of walnut oil, we used transcriptome sequencing technology and metabolome technology to comprehensively analyze the key genes and metabolites involved in oil synthesis of the walnut embryo at 60, 90, and 120 days after pollination (DAP). The results showed that the oil and protein contents increased gradually during fruit development, comprising 69.61% and 18.32% of the fruit, respectively, during ripening. Conversely, the contents of soluble sugar and starch decreased gradually during fruit development, comprising 2.14% and 0.84%, respectively, during ripening. Transcriptome sequencing generated 40,631 unigenes across 9 cDNA libraries. We identified 51 and 25 candidate unigenes related to the biosynthesis of fatty acid and the biosynthesis of triacylglycerol (TAG), respectively. The expression levels of the genes encoding Acetyl-CoA carboxylase (ACCase), long-chain acyl-CoA synthetases (LACS), 3-oxoacyl-ACP synthase II (KASII), and glycerol-3-phosphate acyl transfer (GPAT) were upregulated at 60 DAP relative to the levels at 90 and 120 DAP, while the stearoyl-ACP-desaturase (SAD) and fatty acid desaturase 2 (FAD2) genes were highly abundantly expressed during all walnut developmental periods. We found that ABSCISIC ACID INSENSEITIVE3 (ABI3), WRINKLEDl (WRI1), LEAFY COTYLEDON1 (LEC1), and FUSCA3 (FUS3) may be key transcription factors involved in lipid synthesis. Additionally, the metabolomics analysis detected 706 metabolites derived from 18 samples, among which, 4 are implicated in the TAG synthesis, 2 in the glycolysis pathway, and 5 in the tricarboxylic acid cycle (TCA cycle) pathway. The combined analysis of the related genes and metabolites in TAG synthesis showed that phospholipid:diacylglycerol acyltransferase (PDAT) genes were highly abundantly expressed across walnut fruit developmental periods, and their downstream metabolite TAG gradually accumulated with the progression of fruit development. The FAD2 gene showed consistently higher expression during fruit development, and its downstream metabolites 18:2-PC and 18:3-PC gradually accumulated. The ACCase, LACS, SAD, FAD2, and PDAT genes may be crucial genes required for walnut oil synthesis. Our data will enrich public databases and provide new insights into functional genes related to lipid metabolism in walnut.PMID:36771622 | DOI:10.3390/plants12030538

Evaluation of Sustainable Recycled Products to Increase the Production of Nutraceutical and Antibacterial Molecules in Basil Plants by a Combined Metabolomic Approach

Sat, 11/02/2023 - 12:00
Plants (Basel). 2023 Jan 23;12(3):513. doi: 10.3390/plants12030513.ABSTRACTBACKGROUND: An important goal of modern medicine is the development of products deriving from natural sources to improve environmental sustainability. In this study, humic substances (HS) and compost teas (CTs) extracted from artichoke (ART) and coffee grounds (COF) as recycled biomasses were employed on Ocimum basilicum plants to optimize the yield of specific metabolites with nutraceutical and antibacterial features by applying sustainable strategies.METHODS: The molecular characteristics of compost derivates were elucidated by Nuclear Magnetic Resonance spectroscopy to investigate the structure-activity relationship between organic extracts and their bioactive potential. Additionally, combined untargeted and targeted metabolomics workflows were applied to plants treated with different concentrations of compost extracts.RESULTS: The substances HS-ART and CT-COF improved both antioxidant activity (TEAC values between 39 and 55 μmol g-1) and the antimicrobial efficacy (MIC value between 3.7 and 1.3 μg mL-1) of basil metabolites. The metabolomic approach identified about 149 metabolites related to the applied treatments. Targeted metabolite quantification further highlighted the eliciting effect of HS-ART and CT-COF on the synthesis of aromatic amino acids and phenolic compounds for nutraceutical application.CONCLUSIONS: The combination of molecular characterization, biological assays, and an advanced metabolomic approach, provided innovative insight into the valorization of recycled biomass to increase the availability of natural compounds employed in the medical field.PMID:36771598 | DOI:10.3390/plants12030513

Metabolomics as a Tool to Understand Nano-Plant Interactions: The Case Study of Metal-Based Nanoparticles

Sat, 11/02/2023 - 12:00
Plants (Basel). 2023 Jan 21;12(3):491. doi: 10.3390/plants12030491.ABSTRACTMetabolomics is a powerful tool in diverse research areas, enabling an understanding of the response of organisms, such as plants, to external factors, their resistance and tolerance mechanisms against stressors, the biochemical changes and signals during plant development, and the role of specialized metabolites. Despite its advantages, metabolomics is still underused in areas such as nano-plant interactions. Nanoparticles (NPs) are all around us and have a great potential to improve and revolutionize the agri-food sector and modernize agriculture. They can drive precision and sustainability in agriculture as they can act as fertilizers, improve plant performance, protect or defend, mitigate environmental stresses, and/or remediate soil contaminants. Given their high applicability, an in-depth understanding of NPs' impact on plants and their mechanistic action is crucial. Being aware that, in nano-plant interaction work, metabolomics is much less addressed than physiology, and that it is lacking a comprehensive review focusing on metabolomics, this review gathers the information available concerning the metabolomic tools used in studies focused on NP-plant interactions, highlighting the impact of metal-based NPs on plant metabolome, metabolite reconfiguration, and the reprogramming of metabolic pathways.PMID:36771576 | DOI:10.3390/plants12030491

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