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

Investigating the effects of storage conditions on urinary volatilomes for their reliability in disease diagnosis

Wed, 27/12/2023 - 12:00
Am J Clin Exp Urol. 2023 Dec 15;11(6):481-499. eCollection 2023.ABSTRACTBACKGROUND: Cancer detection presents challenges regarding invasiveness, cost, and reliability. As a result, exploring alternative diagnostic methods holds significant clinical importance. Urinary metabolomic profiling has emerged as a promising avenue; however, its application for cancer diagnosis may be influenced by sample preparation or storage conditions.OBJECTIVE: This study aimed to assess the impact of sample storage and processing conditions on urinary volatile organic compounds (VOCs) profiles and establish a robust standard operating procedure (SOP) for such diagnostic applications.METHODS: Five key variables were investigated: storage temperatures, durations, freeze-thaw cycles, sample collection conditions, and sample amounts. The analysis of VOCs involved stir bar sorptive extraction coupled with thermal desorption-gas chromatography/mass spectrometry (SBSE-TD-GC-MS), with compound identification facilitated by the National Institute of Standards and Technology Library (NIST). Extensive statistical analysis, including combined scatterplot and response surface (CSRS) plots, partial least squares-discriminant analysis (PLS-DA), and probability density function plots (PDFs), were employed to study the effects of the factors.RESULTS: Our findings revealed that urine storage duration, sample amount, temperature, and fasting/non-fasting sample collection did not significantly impact urinary metabolite profiles. This suggests flexibility in urine sample collection conditions, enabling individuals to contribute samples under varying circumstances. However, the influence of freeze-thaw cycles was evident, as VOC profiles exhibited distinct clustering patterns based on the number of cycles. This emphasizes the effect of freeze-thaw cycles on the integrity of urinary profiles.CONCLUSIONS: The developed SOP integrating SBSE-TD-GC-MS and statistical analyses can serve as a valuable tool for analyzing urinary organic compounds with minimal preparation and sensitive detection. The findings also support that urinary VOCs for cancer screening and diagnosis could be a feasible alternative offering a robust, non-invasive, and sensitive approach for cancer screening.PMID:38148934 | PMC:PMC10749378

The nitrogen-dependent GABA pathway of tomato provides resistance to a globally invasive fruit fly

Wed, 27/12/2023 - 12:00
Front Plant Sci. 2023 Dec 7;14:1252455. doi: 10.3389/fpls.2023.1252455. eCollection 2023.ABSTRACTINTRODUCTION: The primary metabolism of plants, which is mediated by nitrogen, is closely related to the defense response to insect herbivores.METHODS: An experimental system was established to examine how nitrogen mediated tomato resistance to an insect herbivore, the oriental fruit fly (Bactrocera dorsalis). All tomatoes were randomly assigned to the suitable nitrogen (control, CK) treatment, nitrogen excess (NE) treatment and nitrogen deficiency (ND) treatment.RESULTS: We found that nitrogen excess significantly increased the aboveground biomass of tomato and increased the pupal biomass of B. dorsalis. Metabolome analysis showed that nitrogen excess promoted the biosynthesis of amino acids in healthy fruits, including γ-aminobutyric acid (GABA), arginine and asparagine. GABA was not a differential metabolite induced by injury by B. dorsalis under nitrogen excess, but it was significantly induced in infested fruits at appropriate nitrogen levels. GABA supplementation not only increased the aboveground biomass of plants but also improved the defensive response of tomato.DISCUSSION: The biosynthesis of GABA in tomato is a resistance response to feeding by B. dorsalis in appropriate nitrogen, whereas nitrogen excess facilitates the pupal weight of B. dorsalis by inhibiting synthesis of the GABA pathway. This study concluded that excess nitrogen inhibits tomato defenses in plant-insect interactions by inhibiting GABA synthesis, answering some unresolved questions about the nitrogen-dependent GABA resistance pathway to herbivores.PMID:38148864 | PMC:PMC10751092 | DOI:10.3389/fpls.2023.1252455

Regulatory mechanism of the six-method massage antipyretic process on lipopolysaccharide-induced fever in juvenile rabbits: A targeted metabolomics approach

Wed, 27/12/2023 - 12:00
Heliyon. 2023 Dec 8;10(1):e23313. doi: 10.1016/j.heliyon.2023.e23313. eCollection 2024 Jan 15.ABSTRACTOBJECTIVE: To investigate the mechanism of the six-method massage antipyretic process (SMAP) and its influence on the body's metabolic state.METHODS: The random number table method was used to divide 24 New Zealand 2-month-old rabbits with qualified basal body temperature into a control group, model group and massage group (n = 8 per group). The model group and massage groups were injected with 0.5 μg/ml lipopolysaccharide (1 ml/kg) into the auricular vein, and the control group was injected with the same amount of normal saline at the same temperature. One hour after modelling, the massage group was given SMAP (opening Tianmen, pushing Kangong, rubbing Taiyang, rubbing Erhougaogu, clearing the Tianheshui and pushing the spine). The change of anal temperature 5 h after moulding was recorded to clarify the antipyretic effect.RESULTS: After modelling, the rectal temperature of the juvenile rabbits in the three groups increased. The rectal temperature of the model group was higher than that of the control group 5 h after modelling, and the rectal temperature of the massage group was lower than that of the model group (P < 0.05). The antipyretic mechanism is related to the regulation of the synthesis of phenylalanine, tyrosine and tryptophan, as well as the pentose phosphate pathway. Compared with the model group, the plasma interleukin (IL)-1, IL-6, interferon-gamma, toll-like receptor 4, nuclear factor κB, the mechanistic target of rapamycin complex 1, indoleamine 2,3-dioxygenase 1, aryl hydrocarbon receptor, liver aspartate transaminase (AST), alanine transaminase (ALT) and l-glutamate dehydrogenase (L-GLDH) expression in the massage group were significantly decreased (P < 0.05). Compared with the model group, the massage group had significantly reduced AST, ALT and L-GLDH expression in plasma (P < 0.05).CONCLUSION: The mechanism of SMAP therapy is related to regulating the expression of peripheral inflammatory factors and metabolic pathways.PMID:38148795 | PMC:PMC10750150 | DOI:10.1016/j.heliyon.2023.e23313

Early Metabolic Disruption and Predictive Biomarkers of Delayed-Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Wed, 27/12/2023 - 12:00
J Proteome Res. 2023 Dec 26. doi: 10.1021/acs.jproteome.3c00575. Online ahead of print.ABSTRACTDelayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of complications and death. Here, we set out to identify high-performance predictive biomarkers of DCI and its underlying metabolic disruptions using metabolomics and lipidomics approaches. This single-center prospective observational study enrolled 61 consecutive patients with severe aSAH; among them, 22 experienced a DCI. Nine patients without aSAH were included as validation controls. Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h after admission. We identified a panel of 20 metabolites that, together, showed high predictive performance for DCI. This panel of metabolites included lactate, cotinine, salicylate, 6 phosphatidylcholines, and 4 sphingomyelins. The interplay of the metabolome and the lipidome found between CSF and plasma in our patients underscores that aSAH and its associated DCI complications can extend beyond cerebral implications, with a peripheral dimension as well. As an illustration, early biological disruptions that might explain the subsequent DCI found systemic hypoxia driven mainly by higher blood lactate, arginine, and proline metabolism likely associated with vascular NO and disrupted ceramide/sphingolipid metabolism. We conclude that targeting early peripheral hypoxia preceding DCI could provide an interesting strategy for the prevention of vascular dysfunction.PMID:38148664 | DOI:10.1021/acs.jproteome.3c00575

High-Throughput Combined Analysis of Saliva Microbiota and Metabolomic Profile in Chinese Periodontitis Patients: A Pilot Study

Tue, 26/12/2023 - 12:00
Inflammation. 2023 Dec 26. doi: 10.1007/s10753-023-01948-6. Online ahead of print.ABSTRACTThe onset and progression of periodontitis involves complicated interactions between the dysbiotic oral microbiota and disrupted host immune-inflammatory response, which can be mirrored by the changes in salivary metabolites profile. This pilot study sought to examine the saliva microbiome and metabolome in the Chinese population by the combined approach of 16s rRNA sequencing and high-throughput targeted metabolomics to discover potential cues for host-microbe metabolic interactions. Unstimulated whole saliva samples were collected from eighteen Stage III and IV periodontitis patients and thirteen healthy subjects. Full-mouth periodontal parameters were recorded. The taxonomic composition of microbiota was obtained by 16s rRNA sequencing, and the metabolites were identified and measured by ultra-high performance liquid chromatography and mass spectrometry-based metabolomic analysis. The oral microbiota composition displayed marked changes where the abundance of 93 microbial taxa differed significantly between the periodontitis and healthy group. Targeted metabolomics identified 103 differential metabolites between the patients and healthy individuals. Functional enrichment analysis demonstrated the upregulation of protein digestion and absorption, histidine metabolism, and nicotinate and nicotinamide metabolism pathways in the dysbiotic microbiota, while the ferroptosis, tryptophan metabolism, glutathione metabolism, and carbon metabolism pathways were upregulated in the patients. Correlation analysis confirmed positive relationships between the clinical parameters, pathogen abundances, and disease-related metabolite levels. The integral analysis of the saliva microbiome and metabolome yielded an accurate presentation of the dysbiotic oral microbiome and functional alterations in host-microbe metabolism. The microbial and metabolic profiling of the saliva could be a potential tool in the diagnosis, prognosis evaluation, and pathogenesis study of periodontitis.PMID:38148454 | DOI:10.1007/s10753-023-01948-6

A horizontal view of primary metabolomes in vegetative desiccation tolerance

Tue, 26/12/2023 - 12:00
Physiol Plant. 2023 Nov-Dec;175(6):e14109. doi: 10.1111/ppl.14109.ABSTRACTVegetative desiccation tolerance (VDT), the ability of such tissues to survive the near complete loss of cellular water, is a rare but polyphyletic phenotype. It is a complex multifactorial trait, typified by universal (core) factors but with many and varied adaptations due to plant architecture, biochemistry and biotic/abiotic dynamics of particular ecological niches. The ability to enter into a quiescent biophysically stable state is what ultimately determines desiccation tolerance. Thus, understanding the metabolomic complement of plants with VDT gives insight into the nature of survival as well as evolutionary aspects of VDT. In this study, we measured the soluble carbohydrate profiles and the polar, TMS-derivatisable metabolomes of 7 phylogenetically diverse species with VDT, in contrast with two desiccation sensitive (DS) species, under conditions of full hydration, severe water deficit stress, and desiccation. Our study confirmed the existence of core mechanisms of VDT systems associated with either constitutively abundant trehalose or the accumulation of raffinose family oligosaccharides and sucrose, with threshold ratios conditioned by other features of the metabolome. DS systems did not meet these ratios. Considerable chemical variations among VDT species suggest that co-occurring but distinct stresses (e.g., photooxidative stress) are dealt with using different chemical regimes. Furthermore, differences in the timing of metabolic shifts suggest there is not a single "desiccation programme" but that subprocesses are coordinated differently at different drying phases. There are likely to be constraints on the composition of a viable dry state and how different adaptive strategies interact with the biophysical constraints of VDT.PMID:38148236 | DOI:10.1111/ppl.14109

Phosphorus deficiency alters root length, acid phosphatase activity, organic acids, and metabolites in root exudates of soybean cultivars

Tue, 26/12/2023 - 12:00
Physiol Plant. 2023 Nov-Dec;175(6):e14107. doi: 10.1111/ppl.14107.ABSTRACTPhosphorus (P) deficiency alters the root morphological and physiological traits of plants. This study investigates how soybean cultivars with varying low-P tolerance values respond to different P levels in hydroponic culture by assessing alterations in root length, acid phosphatase activity, organic acid exudation, and metabolites in root exudates. Three low-P-tolerant cultivars ('Maetsue,' 'Kurotome,' and 'Fukuyutaka') and three low-P-sensitive cultivars ('Ihhon,' 'Chizuka,' and 'Komuta') were grown under 0 (P0) and 258 μM P (P8) for 7 and 14 days after transplantation (DAT). Low-P-tolerant cultivars increased root length by 31% and 119%, which was lower than the 62% and 144% increases in sensitive cultivars under P0 compared to P8 at 7 and 14 DAT, respectively. Acid phosphatase activity in low-P-tolerant cultivars exceeded that in sensitive cultivars by 5.2-fold and 2.0-fold at 7 and 14 DAT. Root exudates from each cultivar revealed 177 metabolites, with higher organic acid exudation in low-P-tolerant than sensitive cultivars under P0. Low-P-tolerant cultivars increased concentrations of specific metabolites (oxalate, GABA, quinate, citrate, AMP, 4-pyridoxate, and CMP), distinguishing them from low-P-sensitive cultivars under P0. The top five metabolomic pathways (purine metabolism, arginine and proline metabolism, TCA cycle, glyoxylate and dicarboxylate metabolism, alanine, aspartate, and glutamate metabolism) were more pronounced in low-P-tolerant cultivars at 14 DAT. These findings indicate that increasing root length was not an adaptation strategy under P deficiency; instead, tolerant cultivars exhibit enhanced root physiological traits, including increased acid phosphatase activity, organic acid exudation, specific metabolite release, and accelerated metabolic pathways under P deficiency.PMID:38148232 | DOI:10.1111/ppl.14107

Heterologous expression of PtAAS1 reveals the metabolic potential of the common plant metabolite phenylacetaldehyde for auxin synthesis in planta

Tue, 26/12/2023 - 12:00
Physiol Plant. 2023 Nov-Dec;175(6):e14078. doi: 10.1111/ppl.14078.ABSTRACTAromatic aldehydes and amines are common plant metabolites involved in several specialized metabolite biosynthesis pathways. Recently, we showed that the aromatic aldehyde synthase PtAAS1 and the aromatic amino acid decarboxylase PtAADC1 contribute to the herbivory-induced formation of volatile 2-phenylethanol and its glucoside 2-phenylethyl-β-D-glucopyranoside in Populus trichocarpa. To unravel alternative metabolic fates of phenylacetaldehyde and 2-phenylethylamine beyond alcohol and alcohol glucoside formation, we heterologously expressed PtAAS1 and PtAADC1 in Nicotiana benthamiana and analyzed plant extracts using untargeted LC-qTOF-MS and targeted LC-MS/MS analysis. While the metabolomes of PtAADC1-expressing plants did not significantly differ from those of control plants, expression of PtAAS1 resulted in the accumulation of phenylacetic acid (PAA) and PAA-amino acid conjugates, identified as PAA-aspartate and PAA-glutamate. Herbivory-damaged poplar leaves revealed significantly induced accumulation of PAA-Asp, while levels of PAA remained unaltered upon herbivory. Transcriptome analysis showed that members of auxin-amido synthetase GH3 genes involved in the conjugation of auxins with amino acids were significantly upregulated upon herbivory in P. trichocarpa leaves. Overall, our data indicates that phenylacetaldehyde generated by poplar PtAAS1 serves as a hub metabolite linking the biosynthesis of volatile, non-volatile herbivory-induced specialized metabolites, and phytohormones, suggesting that plant growth and defense can be balanced on a metabolic level.PMID:38148231 | DOI:10.1111/ppl.14078

Integrated multi-omic data and analyses reveal the response pathways of to high-temperature stress

Tue, 26/12/2023 - 12:00
Physiol Plant. 2023 Nov-Dec;175(6):e14112. doi: 10.1111/ppl.14112.ABSTRACTWith the intensification of the greenhouse effect and the continuous rise of global temperature, high temperatures in summer seriously affect the growth of green onion (Allium fistulosum L.var.caespitosum Makino) and reduce its yield and quality. It is important to study the mechanism of heat tolerance in green onion for selecting and breeding new varieties with high-temperature tolerance. In this study, we used the heat-tolerant green onion variety AF60 and heat-sensitive green onion variety AF35 and measured their physiological indexes under different durations of heat stress. The results showed that high-temperature stress adversely affected the water content, protein composition and antioxidant system of green onion. In addition, a comprehensive analysis using transcriptomics and metabolomics showed that heat-tolerant green onions responded positively to heat stress by up-regulating the expression of heat shock proteins, whereas heat-sensitive green onions responded to heat stress by activating the galactose metabolic pathway and maintained normal physiological activities. This study revealed the physiological performance and high-temperature response pathways of different heat-tolerant green onion cultivars under heat stress. The results further deepen the understanding of the molecular mechanism of green onion's heat stress response.PMID:38148228 | DOI:10.1111/ppl.14112

Comprehensive physiological, transcriptomic, and metabolomic analysis of the key metabolic pathways in millet seedling adaptation to drought stress

Tue, 26/12/2023 - 12:00
Physiol Plant. 2023 Nov-Dec;175(6):e14122. doi: 10.1111/ppl.14122.ABSTRACTDrought is one of the leading environmental constraints that affect the growth and development of plants and, ultimately, their yield and quality. Foxtail millet (Setaria italica) is a natural stress-resistant plant and an ideal model for studying plant drought resistance. In this study, two varieties of foxtail millet with different levels of drought resistance were used as the experimental material. The soil weighing method was used to simulate drought stress, and the differences in growth, photosynthetic physiology, metabolite metabolism, and gene transcriptional expression under drought stress were compared and analyzed. We aimed to determine the physiological and key metabolic regulation pathways of the drought-tolerant millet in resistance to drought stress. The results showed that drought-tolerant millet exhibited relatively stable growth and photosynthetic parameters under drought stress while maintaining a relatively stable level of photosynthetic pigments. The metabolomic, transcriptomic, and gene co-expression network analysis confirmed that the key to adaptation to drought by millet was to enhance lignin metabolism, promote the metabolism of fatty acids to be transformed into cutin and wax, and improve ascorbic acid circulation. These findings provided new insights into the metabolic regulatory network of millet adaptation to drought stress.PMID:38148213 | DOI:10.1111/ppl.14122

The light spectrum differentially influences morphology, physiology and metabolism of Chrysanthemum × morifolium without affecting biomass accumulation

Tue, 26/12/2023 - 12:00
Physiol Plant. 2023 Nov-Dec;175(6):e14080. doi: 10.1111/ppl.14080.ABSTRACTThe development of light emitting diodes (LED) gives new possibilities to use the light spectrum to manipulate plant morphology and physiology in plant production and research. Here, vegetative Chrysanthemum × morifolium were grown at a photosynthetic photon flux density of 230 μmol m-2 s-1 under monochromatic blue, cyan, green, and red, and polychromatic red:blue or white light with the objective to investigate the effect on plant morphology, gas exchange and metabolic profile. After 33 days of growth, branching and leaf number increased from blue to red light, while area per leaf, leaf weight fraction, flavonol index, and stomatal density and conductance decreased, while dry matter production was mostly unaffected. Plants grown under red light had decreased photosynthesis performance compared with blue or white light-grown plants. The primary and secondary metabolites, such as organic acids, amino acids and phenylpropanoids (measured by non-targeted metabolomics of polar metabolites), were regulated differently under the different light qualities. Specifically, the levels of reduced ascorbic acid and its oxidation products, and the total ascorbate pool, were significantly different between blue light-grown plants and plants grown under white or red:blue light, which imply photosynthesis-driven alterations in oxidative pressure under different light regimens. The overall differences in plant phenotype, inflicted by blue, red:blue or red light, are probably due to a shift in balance between regulatory pathways controlled by blue light receptors and/or phytochrome. Although morphology, physiology, and metabolism differed substantially between plants grown under different qualities of light, these changes had limited effects on biomass accumulation.PMID:38148199 | DOI:10.1111/ppl.14080

Quantification of antigen of <em>Mycoplasma capricolum</em> subsp. <em>capripneumoniae</em> by optical assay

Tue, 26/12/2023 - 12:00
Sheng Wu Gong Cheng Xue Bao. 2023 Dec 25;39(12):4874-4886. doi: 10.13345/j.cjb.230178.ABSTRACTMycoplasma capricolum subsp. capripneumoniae (Mccp) is the cause of contagious caprine pleuropneumonia (CCPP) in goats. Inactivated vaccines and capsular polysaccharide (CPS) indirect hemagglutination reagents are available for prevention and serological detection, but high culture costs and complex antigen quantification have been plagued by production staff. In order to solve these problems in production practice, a sugar fermentation medium with an initial pH value of 7.8, which could improve the production of two antigens simultaneously, was screened out by changing the initial pH value based on previous Mccp metabolomics analysis. Since phenol red can be identified by UV absorption spectrum and cetyltrimethylammonium bromide (CTAB) can bind to anionic capsular polysaccharide, a UV spectrum measurement method for analyzing the culture stage reached by Mccp and a CTAB precipitation test for relative quantification of capsular polysaccharide antigen content in the fermentation broth were established. The UV spectrum observation method can guide the production of Mccp according to the growth curve of Mccp, which greatly reduces the monitoring time of the traditional CCU method and improves the accuracy of the original eye-observation method. The established CTAB precipitation test can complete the monitoring of CPS content within 5 hours, which greatly reduces the time required compared with the traditional differential technique, and its accuracy was verified by the phenol-sulfuric acid method. The optimized culture medium and the two correlation comparison methods established in this study can effectively reduce the production cost of Mccp and improve the production efficiency. The two assays have been used in the research at our laboratory, which provides experimental data for further improvement of the production process of CCPP inactivated vaccine and capsular polysaccharide as well as rapid quantification.PMID:38147988 | DOI:10.13345/j.cjb.230178

PuRenDan alleviates type 2 diabetes mellitus symptoms by modulating the gut microbiota and its metabolites

Tue, 26/12/2023 - 12:00
J Ethnopharmacol. 2023 Dec 24:117627. doi: 10.1016/j.jep.2023.117627. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: PuRenDan (PRD) is a traditional Chinese medicine formula comprising five herbs that have been traditionally used to treat type 2 diabetes mellitus (T2DM). While PRD has been shown to be effective in treating T2DM in clinical and animal studies, the mechanisms by which it works on the gut microbiome and metabolites related to T2DM are not well understood.AIM OF THE STUDY: The objective of this study was to partially elucidate the mechanism of PRD in treating T2DM through analyses of the gut microbiota metagenome and metabolome.MATERIALS AND METHODS: Sprague-Dawley rats were fed high-fat diets (HFDs) and injected with low-dose streptozotocin (STZ) to replicate T2DM models. Then the therapeutic effects of PRD were evaluated by measuring clinical markers such as blood glucose, insulin resistance (IR), lipid metabolism biomarkers (total cholesterol, low-density lipoprotein, non-esterified fatty acids, and triglycerides), and inflammatory factors (tumor necrosis factor alpha, interleukin-6 [IL-6], interferon gamma, and IL-1β). Colon contents were collected, and metagenomics, combined with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry metabolic profiling, was performed to evaluate the effects of T2DM and PRD on gut microbiota and its metabolites in rats. Spearman analysis was used to calculate the correlation coefficient among different microbiota, clinical indices, and metabolites.RESULTS: PRD exhibited significant improvement in blood glucose and IR, and reduced serum levels of lipid metabolism biomarkers and inflammatory factors. Moreover, the diversity and abundance of gut microbiota undergo significant changes in rats with T2DM that PRD was able to reverse. The gut microbiota associated with T2DM including Rickettsiaceae bacterium 4572_127, Psychrobacter pasteurii, Parabacteroides sp. CAG409, and Paludibacter propionicigenes were identified. The gut microbiota most closely related to PRD were Prevotella sp. 10(H), Parabacteroides sp. SN4, Flavobacteriales bacterium, Bacteroides massiliensis, Alistipes indistinctus, and Ruminococcus flavefaciens. Additionally, PRD regulated the levels of gut microbiota metabolites including pantothenic acid, 1-Methylhistamine, and 1-Methylhistidine; these affected metabolites were involved in pantothenate and coenzyme A biosynthesis, histidine metabolism, and secondary bile acid biosynthesis. Correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes.CONCLUSION: Our study provides insights into the gut microbiota and its metabolites of PRD therapy for T2DM. It clarifies the role of gut microbiota and the metabolites in the pathogenesis of T2DM, highlighting the potential of PRD for the treatment of this disease.PMID:38147943 | DOI:10.1016/j.jep.2023.117627

6PPD-quinone exposure induces neuronal mitochondrial dysfunction to exacerbate Lewy neurites formation induced by α-synuclein preformed fibrils seeding

Tue, 26/12/2023 - 12:00
J Hazard Mater. 2023 Dec 19;465:133312. doi: 10.1016/j.jhazmat.2023.133312. Online ahead of print.ABSTRACTThe emerging toxicant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) is of wide concern due to its ubiquitous occurrence and high toxicity. Despite regular human exposure, limited evidence exists about its presence in the body and potential health risks. Herein, we analyzed cerebrospinal fluid (CSF) samples from Parkinson's disease (PD) patients and controls. The CSF levels of 6PPD-Q were twice as high in PD patients compared to controls. Immunostaining assays performed with primary dopaminergic neurons confirm that 6PPD-Q at environmentally relevant concentrations can exacerbate the formation of Lewy neurites induced by α-synuclein preformed fibrils (α-syn PFF). Assessment of cellular respiration reveals a considerable decrease in neuronal spare respiratory and ATP-linked respiration, potentially due to changes in mitochondrial membrane potential. Moreover, 6PPD-Q-induced mitochondrial impairment correlates with an upsurge in mitochondrial reactive oxygen species (mROS), and Mito-TEMPO-driven scavenging of mROS can lessen the amount of pathologic phospho-serine 129 α-synuclein. Untargeted metabolomics provides supporting evidence for the connection between 6PPD-Q exposure and changes in neuronal metabolite profiles. In-depth targeted metabolomics further unveils an overall reduction in glycolysis metabolite pool and fluctuations in the quantity of TCA cycle intermediates. Given its potentially harmful attributes, the presence of 6PPD-Q in human brain could potentially be a risk factor for PD.PMID:38147746 | DOI:10.1016/j.jhazmat.2023.133312

Discovering Nature's shield: Metabolomic insights into green zinc oxide nanoparticles Safeguarding Brassica parachinensis L. from cadmium stress

Tue, 26/12/2023 - 12:00
Plant Physiol Biochem. 2023 Nov 2;206:108126. doi: 10.1016/j.plaphy.2023.108126. Online ahead of print.ABSTRACTHeavy metal cadmium (Cd) hinders plants' growth and productivity by causing different morphological and physiological changes. Nanoparticles (NPs) are promising for raising plant yield and reducing Cd toxicity. Nonetheless, the fundamental mechanism of nanoparticle-interfered Cd toxicity in Brassica parachineses L. remains unknown. A novel ZnO nanoparticle (ZnO-NPs) was synthesized using a microalgae strain (Chlorella pyrenoidosa) through a green process and characterized by different standard parameters through TEM, EDX, and XRD. This study examines the effect of different concentrations of ZnO-NPs (50 and 100 mgL-1) in B. parachineses L. under Cd stress through ultra-high-performance liquid chromatography/high-resolution mass spectrometry-based untargeted metabolomics profiling. In the presence of Cd toxicity, foliar spraying with ZnO-NPs raised Cu, Fe, Zn, and Mg levels in the roots and/or leaves, improved seedling development, as demonstrated by increased plant height, root length, and shoot and root fresh weight. Furthermore, the ZnO-NPs significantly enhanced the photosynthetic pigments and changed the antioxidant activities of the Cd-treated plants. Based on a metabolomics analysis, 481 untargeted metabolites were accumulated in leaves under normal and Cd-stressed conditions. These metabolites were highly enriched in producing organic acids, amino acids, glycosides, flavonoids, nucleic acids, and vitamin biosynthesis. Surprisingly, ZnO-NPs restored approximately 60% of Cd stress metabolites to normal leaf levels. Our findings suggest that green synthesized ZnO-NPs can balance ions' absorption, modulate the antioxidant activities, and restore more metabolites associated with plant growth to their normal levels under Cd stress. It can be applied as a plant growth regulator to alleviate heavy metal toxicity and improve crop yield in heavy metal-contaminated regions.PMID:38147709 | DOI:10.1016/j.plaphy.2023.108126

Genetic polymorphisms and expression of Rhesus blood group RHCE are associated with 2,3-bisphosphoglycerate in humans at high altitude

Tue, 26/12/2023 - 12:00
Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2315930120. doi: 10.1073/pnas.2315930120. Epub 2023 Dec 26.ABSTRACTRed blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity.PMID:38147558 | DOI:10.1073/pnas.2315930120

Long-term effects of oil contamination on soil quality and metabolic function

Tue, 26/12/2023 - 12:00
Environ Geochem Health. 2023 Dec 26;46(1):13. doi: 10.1007/s10653-023-01779-2.ABSTRACTWidespread soil contamination with oil and the toxicity of petroleum hydrocarbons to soil biota make it extremely important to study microbial responses to oil stress. Soil metabolites reflect the main metabolic pathways in the soil microbial community. The examination of changes in the soil metabolic profile and metabolic function is essential for a better understanding of the nature of the pollution and restoration of the disturbed soils. The present study aimed to assess the long-term effect of oil on the ecological state of the soil, evaluate quantitative and qualitative differences in metabolite composition between soil contaminated with oil and non-contaminated soil, and reveal biologically active metabolites that are related to oil contamination and can be used for contamination assessment. A long-term field experiment was conducted to examine the effects of various oil concentrations on the biochemical properties and metabolic profile of the soil. Podzolic soil contaminated with oil demonstrated the long-term inhibition of soil biological activity and vegetation. Oil affected the metabolic activity of soil fungi increasing the production of toxic metabolites. A metabolomic approach was employed to determine soil metabolites. The metabolite profile was found to vary greatly between oil-contaminated and non-contaminated soils. Carbohydrates had the largest number of metabolites negatively affected by oil, while the content of organic acids, phenolic compounds, and terpenoids was mainly increased in oil-contaminated soil. The evaluation of the long-term impact of oil on microbial metabolism can make a valuable contribution to the assessment of soil quality and the activity of soil microorganisms being under stress from oil pollution. The results contribute to a further understanding of the role of microorganisms in the ecological functions of contaminated soil, which can be useful in the development of rehabilitation strategies for disturbed sites.PMID:38147148 | DOI:10.1007/s10653-023-01779-2

Intercropping of Narrow-Leafed Lupin (<em>Lupinus angustifolius</em> L.) and Barley (<em>Hordeum vulgare</em> L.) Affects the Flavonoid Composition of Both Crops

Tue, 26/12/2023 - 12:00
J Agric Food Chem. 2023 Dec 26. doi: 10.1021/acs.jafc.3c03684. Online ahead of print.ABSTRACTBarley (Hordeum vulgare L.) is a common cereal crop in agricultural production and is often included in legume-cereal intercropping. Flavonoids, a major class of secondary metabolites found in barley, are involved in plant defense and protection. However, the effect of intercropping on barley flavonoids remains unknown. Herein, an intercropping system involving barley and lupin (Lupinus angustifolius L.) was studied. Intercropping increased the level of luteolin in lupin roots. Lupin-barley intercropping considerably increased genistein, rutin, and apigenin in barley shoots. Genistein and apigenin were also detected in intercropped barley roots and rhizosphere soil. The three flavonoids have been reported as defense compounds, suggesting that lupin triggers a defense response in barley to strengthen its survival ability.PMID:38146912 | DOI:10.1021/acs.jafc.3c03684

Metabolomics at the tumor microenvironment interface: Decoding cellular conversations

Tue, 26/12/2023 - 12:00
Med Res Rev. 2023 Dec 26. doi: 10.1002/med.22010. Online ahead of print.ABSTRACTCancer heterogeneity remains a significant challenge for effective cancer treatments. Altered energetics is one of the hallmarks of cancer and influences tumor growth and drug resistance. Studies have shown that heterogeneity exists within the metabolic profile of tumors, and personalized-combination therapy with relevant metabolic interventions could improve patient response. Metabolomic studies are identifying novel biomarkers and therapeutic targets that have improved treatment response. The spatial location of elements in the tumor microenvironment are becoming increasingly important for understanding disease progression. The evolution of spatial metabolomics analysis now allows scientists to deeply understand how metabolite distribution contributes to cancer biology. Recently, these techniques have spatially resolved metabolite distribution to a subcellular level. It has been proposed that metabolite mapping could improve patient outcomes by improving precision medicine, enabling earlier diagnosis and intraoperatively identifying tumor margins. This review will discuss how altered metabolic pathways contribute to cancer progression and drug resistance and will explore the current capabilities of spatial metabolomics technologies and how these could be integrated into clinical practice to improve patient outcomes.PMID:38146814 | DOI:10.1002/med.22010

Preterm Birth: Screening and Prediction

Tue, 26/12/2023 - 12:00
Int J Womens Health. 2023 Dec 21;15:1981-1997. doi: 10.2147/IJWH.S436624. eCollection 2023.ABSTRACTPreterm birth (PTB) affects approximately 10% of births globally each year and is the most significant direct cause of neonatal death and of long-term disability worldwide. Early identification of women at high risk of PTB is important, given the availability of evidence-based, effective screening modalities, which facilitate decision-making on preventative strategies, particularly transvaginal sonographic cervical length (CL) measurement. There is growing evidence that combining CL with quantitative fetal fibronectin (qfFN) and maternal risk factors in the extensively peer-reviewed and validated QUanititative Innovation in Predicting Preterm birth (QUiPP) application can aid both the triage of patients who present as emergencies with symptoms of preterm labor and high-risk asymptomatic women attending PTB surveillance clinics. The QUiPP app risk of delivery thus supports shared decision-making with patients on the need for increased outpatient surveillance, in-patient treatment for preterm labor or simply reassurance for those unlikely to deliver preterm. Effective triage of patients at preterm gestations is an obstetric clinical priority as correctly timed administration of antenatal corticosteroids will maximise their neonatal benefits. This review explores the predictive capacity of existing predictive tests for PTB in both singleton and multiple pregnancies, including the QUiPP app v.2. and discusses promising new research areas, which aim to predict PTB through cervical stiffness and elastography measurements, metabolomics, extracellular vesicles and artificial intelligence.PMID:38146587 | PMC:PMC10749552 | DOI:10.2147/IJWH.S436624

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