Alterations In Metabolic Pathways Research Articles

THU486 Identification Of Metabolic And Molecular Mechanisms Driving Estrogen Receptor Positive Breast Cancer Disparities Using A Machine-Learning Pipeline

Abstract Disclosure: A. Santaliz Casiano: None. D. Mehta: None. H. Patel: None. G. Rauscher: None. J. Kim: None. J.M. Frasor: None. K. Hoskins: None. Background: African American (AA) women in the United States have a 40% higher breast cancer mortality rate compared with Non-Hispanic White (NHW) women. The survival disparity is particularly striking among ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ positive breast cancer. Methods: We collected pretreatment plasma from AA and NHW ER+ breast cancer cases and cancer-free controls to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC-MS) to identify metabolites that may be altered in the different racial groups. Statistical methods combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from TCGA. Results: We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed changes in metabolites associated with amino acid metabolism, while fatty acid metabolism was significantly enriched in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant association with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene NELFE with histone methyltransferase activity was associated with poor survival exclusively for AA individuals. Conclusion: We employed a comprehensive and novel approach that integrates multiple machine learning methods and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women, and may ultimately lead to identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer, and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities. Presentation: Thursday, June 15, 2023

Unraveling adipose tissue proteomic landscapes in severe obesity: insights into metabolic complications and potential biomarkers.

In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies.NEW & NOTEWORTHY This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.

Internalization, physiological responses and molecular mechanisms of lettuce to polystyrene microplastics of different sizes: Validation of simulated soilless culture

Microplastics (MPs) exists widely in the environment, and the resulting pollution of MPs has become a global environmental problem. Plants can absorb MPs through their roots. However, studies on the mechanism of the effect of root exposure to different size MPs on vegetables are limited. Here, we use Polystyrene (PS) MPs with different particle sizes to investigate the internalization, physiological response and molecular mechanism of lettuce to MPs. MPs may accumulate in large amounts in lettuce roots and migrate to the aboveground part through the vascular bundle, while small particle size MPs (SMPs, 100 nm) have stronger translocation ability than large particle size MPs (LMPs, 500 nm). MPs can cause physiological and biochemical responses and transcriptome changes in lettuce. SMPs and LMPs resulted in reduced biomass (38.27 % and 48.22 % reduction in fresh weight); caused oxidative stress (59.33 % and 47.74 % upregulation of SOD activity in roots) and differential gene expression (605 and 907 DEGs). Signal transduction, membrane transport and alteration of synthetic and metabolic pathways may be the main causes of physiological toxicity of lettuce. Our study provides important information for understanding the behavior and fate of MPs in edible vegetables, especially the physiological toxicity of MPs to edible vegetables, in order to assess the potential threat of MPs to food safety and agricultural sustainable development.

Angelica polysaccharides relieve blood glucose levels in diabetic KKAy mice possibly by modulating gut microbiota: an integrated gut microbiota and metabolism analysis

BackgroundAngelica polysaccharides (AP) have numerous benefits in relieving type 2 diabetes (T2D). However, the underlying mechanisms have yet to be fully understood. Recent many reports have suggested that altering gut microbiota can have adverse effects on the host metabolism and contribute to the development of T2D. Here, we successfully established the T2D model using the male KKAy mice with high-fat and high-sugar feed. Meanwhile, the male C57BL/6 mice were fed with a normal feed. T2D KKAy mice were fed either with or without AP supplementation. In each group, we measured the mice's fasting blood glucose, weight, and fasting serum insulin levels. We collected the cecum content of mice, the gut microbiota was analyzed by targeted full-length 16S rRNA metagenomic sequencing and metabolites were analyzed by untargeted-metabolomics.ResultsWe found AP effectively alleviated glycemic disorders of T2D KKAy mice, with the changes in gut microbiota composition and function. Many bacteria species and metabolites were markedly changed in T2D KKAy mice and reversed by AP. Additionally, 16 altered metabolic pathways affected by AP were figured out by combining metagenomic pathway enrichment analysis and metabolic pathway enrichment analysis. The key metabolites in 16 metabolic pathways were significantly associated with the gut microbial alteration. Together, our findings showed that AP supplementation could attenuate the diabetic phenotype. Significant gut microbiota and gut metabolite changes were observed in the T2D KKAy mice and AP intervention.ConclusionsAdministration of AP has been shown to improve the composition of intestinal microbiota in T2D KKAy mice, thus providing further evidence for the potential therapeutic application of AP in the treatment of T2D.

Assessing Metabolic Differences Associated with Exposure to Polybrominated Biphenyl and Polychlorinated Biphenyls in the Michigan PBB Registry.

Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB in utero or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. Mean levels were [standard deviation (SD): 13.9] for PBB-153 and (SD: 0.788) for . Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) ], respectively. There were 2,861 features associated with (FDR ). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with levels (level 1 evidence). Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657.

Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

GC-MS based comparative metabolomic analysis of human cancellous bone reveals the critical role of linoleic acid metabolism in femur head necrosis.

Femur head necrosis (FHN) is a challenging clinical disease with unclear underlying mechanism, which pathologically is associated with disordered metabolism. However, the disordered metabolism in cancellous bone of FHN was never analyzed by gas chromatography-mass spectrometry (GC-MS). To elucidate altered metabolism pathways in FHN and identify putative biomarkers for the detection of FHN. We recruited 26 patients with femur head necrosis and 22 patients with femur neck fracture in this study. Cancellous bone tissues from the femoral heads were collected after the surgery and were analyzed by GC-MS based untargeted metabolomics approach. The resulting data were analyzed via uni- and multivariate statistical approaches. The changed metabolites were used for the pathway analysis and potential biomarker identification. Thirty-seven metabolites distinctly changed in FHN group were identified. Among them, 32 metabolites were upregulated and 5 were downregulated in FHN. The pathway analysis showed that linoleic acid metabolism were the most relevant to FHN pathology. On the basis of metabolites network, L-lysine, L-glutamine and L-serine were deemed as the junctions of the whole metabolites. Finally, 9,12-octadecadienoic acid, inosine, L-proline and octadecanoic acid were considered as the potential biomarkers of FHN. This study provides a new insight into the pathogenesis of FHN and confirms linoleic acid metabolism as the core.

Metabolic profiling of Apostichopus japonicus body wall exposed to a typical type of PBDEs: potential health risks and impact on sea cucumber health

IntroductionSea cucumbers are cultivated mainly for their valuable body wall. Polybrominated diphenyl ethers are common persistent pollutants in sea waters with known impacts on aquatic animals nonetheless not yet studied for the body wall of sea cucumbers.MethodsUsing ltra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Triple-TOF-MS), we investigated the metabolic impact of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on the body wall of Apostichopus japonicus. etabolite changes and metabolic pathway alterations were assessed in response to three distinct concentrations of BDE-47: 0.1 µg/L, 1.0 µg/L, and 10.0 µg/L.REsultsExposure to BDE-47 led to notable alterations in the metabolic profiles of the body wall. A total of 95~102 metabolites in the 0.1 ~ 10.0 µg/L BDE-47 treated group were altered significantly, and various disrupted metabolic pathways were identified and characterized. These metabolites and metabolic pathways were mainly involved in lipid metabolism, energy metabolism, immunity, oxidative stress, inflammation, and neurotoxicity.DiscussionThe findings of our study shed light on the potential health risks that polybrominated diphenyl ethers present to sea cucumbers. This underscores the imperative for both researchers and policymakers to delve deeper into further investigations and studies. These results indicate the necessity for enhanced monitoring and management practices within the sea cucumber aquaculture industry to mitigate the impact of these persistent organic pollutants and protect the health and safety of this valuable resource.

Metabolic signature for a dysbiotic microbiome in the female genital tract: A systematic review and meta-analysis.

The vaginal microbiome (VMB) is a critical determinant of reproductive health, where a microbial shift towards a dysbiotic environment has implications for susceptibility to, and clinical presentation of sexually transmitted infections (STIs). Metabolomicprofiling of the vaginal microenvironment has led to the identification of metabolic responses to clinical conditions of dysbiosis. However, no studies have examined metabolic markers that are common across conditions and can serve as a signature for vaginal dysbiosis. We have conducted a comprehensive systematic review and meta-analysis to identify consistently deregulated metabolites along with their impact on host and microbial metabolism during dysbiosis. We employed two complementary approaches including a vote counting analysis for all eligible studies identified in the systematic review, in addition to a meta-analysis for a subset of studies with sufficient available data. Significantly deregulated metabolites were then selected for pathway enrichment analysis. Our results revealed a total of 502 altered metabolites reported across 10 dysbiotic conditions from 16 studies. Following a rigorous, collective analysis, six metabolites which were consistently downregulated and could be generalized to all dysbiotic conditions were identified. In addition, five downregulated and oneupregulated metabolite was identified from a bacterial vaginosis (BV) focused sub-analysis. These metabolites have the potential to serve as a metabolic signature for vaginal dysbiosis. Their role in eight altered metabolic pathways indicates a disruption of amino acid, carbohydrate, and energy metabolism during dysbiosis. Based on this analysis, we propose a schematic model outlining the common metabolic perturbations associated with vaginal dysbiosis, which can be potential targets for therapeutics and prophylaxis.

Impaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD. A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD). Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p<0.001) of the presence of coronary calcium in women with SLE. The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE. INSERM and Sorbonne Université.

Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats.

Late-onset depression (LOD) is defined as primary depression that first manifests after the age of 65. Luteolin (LUT) is a natural flavonoid that has shown promising antidepressant effects and improvement in neurological function in previous studies. In this study, we utilized UPLC-MS/MS non-targeted metabolomics techniques, along with molecular docking technology and experimental validation, to explore the mechanism of LUT in treating LOD from a metabolomics perspective. The behavioral results of our study demonstrate that LUT significantly ameliorated anxiety and depression-like behaviors while enhancing cognitive function in LOD rats. Metabolomic analysis revealed that the effects of LUT on LOD rats were primarily mediated through the glycerophospholipid metabolic pathway in the hippocampus and prefrontal cortex. The levels of key lipid metabolites, phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), in the glycerophospholipid metabolic pathway were significantly altered by LUT treatment, with PC and PE showing significant correlations with behavioral indices. Molecular docking analysis indicated that LUT had strong binding activity with phosphatidylserine synthase 1 (PTDSS1), phosphatidylserine synthase 2 (PTDSS2), and phosphatidylserine decarboxylase (PISD), which are involved in the transformation and synthesis of PC, PE, and PS. Lastly, our study explored the reasons for the opposing trends of PC, PE, and PS in the hippocampus and prefrontal cortex from the perspective of autophagy, which may be attributable to the bidirectional regulation of autophagy in distinct brain regions. Our results revealed significant alterations in the glycerophospholipid metabolism pathways in both the hippocampus and prefrontal cortex of LOD rats. Moreover, LUT appears to regulate autophagy disorders by specifically modulating glycerophospholipid metabolism in different brain regions of LOD rats, consequently alleviating depression-like behavior in these animals.

Temperature Modulation of MOS Sensors for Enhanced Detection of Volatile Organic Compounds

Disease diagnosis through biological fluids, particularly exhaled breath analysis, has gained increasing importance. Volatile organic compounds (VOCs) present in exhaled breath offer diagnostic potential as they reflect altered and disease-specific metabolic pathways. While gas chromatography–mass spectrometry (GC–MS) has been traditionally used for VOCs detection, electronic noses have emerged as a promising alternative for disease screening. Metal oxide semiconductor (MOS) sensors play an essential role in these devices due to their simplicity and cost-effectiveness. However, their limited specificity and sensitivity pose challenges for accurate diagnosis at lower VOCs concentrations, typical of exhaled breath. To address specificity and sensitivity issues, temperature modulation (TM) has been proposed in this paper, introducing a custom-developed electronic nose based on multiple and heterogeneous gas sensors located within an analysis chamber. Four different TM patterns (i.e., square, sine, triangular, and a combination of square and triangular) were applied to the gas sensors to test their response to three different analytes at three distinct concentrations. Data were analyzed by extracting meaningful features from the sensor raw data, and dimensionality reduction using principal component analysis (PCA) was performed. The results demonstrated distinct clusters for each experimental condition, indicating successful discrimination of analytes and concentrations. In addition, an analysis of which set of sensors and modulation pattern yielded the best results was performed. In particular, the most promising TM pattern proved to be the square and triangular combination, with optimal discrimination accuracy between both concentrations and analytes. One specific sensor, namely, TGS2600 from Figaro USA, Inc., provided the best performance. While preliminary results highlighted the potential of TM to improve the sensitivity of gas sensors in electronic nose devices, paving the way for further advancements in the field of exhaled breath analysis.

Physiological, metabolomic, and transcriptomic reveal metabolic pathway alterations in Gymnocypris przewalskii due to cold exposure

Teleost fish have evolved various adaptations that allow them to tolerate cold water conditions. However, the underlying mechanism of this adaptation is poorly understood in Tibetan Plateau fish. RNA-seq combined with liquid chromatography‒mass spectrometry (LC‒MS/MS) metabolomics was used to investigate the physiological responses of a Tibetan Plateau-specific teleost, Gymnocypris przewalskii, under cold conditions. The 8-month G. przewalskii juvenile fish were exposed to cold (4 ℃, cold acclimation, CA) and warm (17 ℃, normal temperature, NT) temperature water for 15 days. Then, the transcript profiles of eight tissues, including the brain, gill, heart, intestine, hepatopancreas, kidney, muscle, and skin, were evaluated by transcriptome sequencing. The metabolites of the intestine, hepatopancreas, and muscle were identified by LC‒MS/MS. A total of 5,745 differentially expressed genes (DEGs) were obtained in the CA group. The key DEGs were annotated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The DEGs from the eight tissues were significantly enriched in spliceosome pathways, indicating that activated alternative splicing is a critical biological process that occurs in the tissues to help fish cope with cold stress. Additionally, 82, 97, and 66 differentially expressed metabolites were identified in the intestine, hepatopancreas, and muscle, respectively. Glutathione metabolism was the only overlapping significant pathway between the transcriptome and metabolome analyses in these three tissues, indicating that an activated antioxidative process was triggered during cold stress. In combination with the multitissue transcriptome and metabolome, we established a physiology-gene‒metabolite interaction network related to energy metabolism during cold stress and found that gluconeogenesis and long-chain fatty acid metabolism played critical roles in glucose homeostasis and energy supply.

Inulin supplementation increases the differential metabolites and metabolic pathway in Baird's tapirs (Tapirus bairdii).

The prevalence of prebiotic has increased substantially over the past decades. Little is known on its metabolic effects in zoo herbivores. We investigated the difference in faecal metabolites to characterize the composition and pathways involved after feeding inulin in zoo Baird's tapirs (Tapirus bairdii). Faecal samples were collected from before inulin treatment group and after treatment groups in six adult tapirs and analysed using untargeted liquid chromatography-mass spectrometry methods. The differential metabolites identified and metabolic pathways involved were analysed using KEGG annotation. The results demonstrated significant alterations in faecal metabolites and metabolic pathways in comparison to the control group. The amounts of differential metabolites and metabolic pathways tended to enrich with time after the treatment. We found that tryptophan and purine metabolism were relevant to the important metabolic pathways of the metabolite differences. The findings suggest that inulin may have potential applications in captive wildlife, which may provide insights into the effects of prebiotic supplementation on gut metabolites and highlights further research in this field.

Abscisic acid promotes plant acclimation to the combination of salinity and high light stress

Plants encounter combinations of different abiotic stresses such as salinity (S) and high light (HL). These environmental conditions have a detrimental effect on plant growth and development, posing a threat to agricultural production. Metabolic changes play a crucial role in enabling plants to adapt to fluctuations in their environment. Furthermore, hormones such as abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) have been previously identified as regulators of plant responses to different abiotic stresses. Here we studied the response of Arabidopsis wild type (Col and Ler) plants and mutants impaired in hormone biosynthesis (aba2-11 and aba1-1 in ABA, aos in JA and sid2 in SA) to the combination of S and HL (S + HL). Our findings showed that aba2-11 plants displayed reduced growth, impaired photosystem II (PSII) function, increased leaf damage, and decreased survival compared to Col when subjected to stress combination. However, aos and sid2 mutants did not display significant changes in response to S + HL compared to Col, indicating a key role for ABA in promoting plant tolerance to S + HL and suggesting a marginal role for JA and SA in this process. In addition, we revealed differences in the metabolic response of plants to S + HL compared to S or HL. The analysis of altered metabolic pathways under S + HL suggested that the accumulation of flavonoids is ABA-dependent, whereas the accumulation of branched-chain amino acids (BCAAs) and proline is ABA-independent. Therefore, our study uncovered a key function for ABA in regulating the accumulation of different flavonoids in plants during S + HL.

Understanding COVID-19 progression with longitudinal peripheral blood mononuclear cell proteomics: Changes in the cellular proteome over time

The clinical presentation of COVID-19 is highly variable, and understanding the underlying biological processes is crucial. This study utilized a proteomic analysis to investigate dysregulated processes in the peripheral blood mononuclear cells of patients with COVID-19 compared to healthy volunteers. Samples were collected at different stages of the disease, including hospital admission, after 7days of hospitalization, and 30days after discharge. Metabolic pathway alterations and increased abundance of neutrophil-related proteins were observed in patients. Patients progressing to critical illness had significantly low-abundance proteins in the pentose phosphate and glycolysis pathways compared with those presenting clinical recovery. Important biological processes, such as fatty acid concentration and glucose metabolism disorder, remained altered even after 30days of hospital discharge. Temporal proteomic changes revealed distinct pathways in critically ill and non-critically ill patients. Our study emphasizes the significance of longitudinal cellular proteomic studies in identifying disease progression-related pathways and persistent protein changes post-hospitalization.

Unravelling the anti-inflammatory and antioxidant effects of standardized green and black caffeinated coffee, tea, and their mixtures in an obese male rat model: Insights from biochemical, metabolomic, and histopathological analyses.

Obesity is one of the major metabolic syndrome risk factors upon which altered metabolic pathways follow. This study aimed to discern altered metabolic pathways associated with obesity and to pinpoint metabolite biomarkers in serum of obese rats fed on high fructose diet using metabolomics. Further, the effect of standardized green versus black caffeinated aqueous extracts (tea and coffee) in controlling obesity and its comorbidities through monitoring relevant serum biomarkers viz. Leptin, adiponectin, spexin, malondialdehyde, total antioxidant capacity. Liver tissue oxidative stress (catalase, super oxide dismutase and glutathione) and inflammation (IL-1β and IL-6) markers were assessed for green coffee and its mixture with green tea. Results revealed improvement of all parameters upon treatments with more prominence for those treated with green caffeinated extract (coffee and tea) especially in mixture. Upon comparing with obese rat group, the green mixture of coffee and tea exhibited anti-hyperlipidemic action through lowering serum triglycerides by 35.0% and elevating high density lipoprotein by 71.0%. Black tea was likewise effective in lowering serum cholesterol and low density lipoprotein by 28.0 and 50.6%, respectively. GC-MS- based metabolomics of rat serum led to the identification of 34 metabolites with obese rat serum enriched in fatty acids (oleamide).

Adaptive response of triploid Fujian oyster (Crassostrea angulata) to nanoplastic stress: Insights from physiological, metabolomic, and microbial community analyses

Triploid Fujian oyster (Crassostrea angulata) is crucial to aquaculture and coastal ecosystems because of its accelerated growth and heightened resilience against environmental stressors. In light of the increasing prevalence of nanoplastic pollution in the ocean, understanding its potential impact on this organism, particularly its adaptive responses, is of paramount importance. Despite this, the effects of nanoplastic pollution on the physiology of C. angulata remain largely unexplored. In this study, we explored the responses of triploid Fujian oysters to nanoplastic stress during a 14-day exposure period, employing an integrative methodology that included physiological, metabolomic, and 16S rRNA sequencing analyses. Our results demonstrate that the oysters exhibit a strong adaptive response to nanoplastic exposure, characterized by alterations in enzyme activity, metabolic pathways, and microbial community composition, indicative of an adaptive recovery state as opposed to a disordered state. Oysters subjected to elevated nanoplastic levels exhibited adaptive responses primarily by boosting the activity of the antioxidant enzyme catalase and elevating the levels of antioxidants such as adenosine, 3-(4-hydroxyphenyl)pyruvate, D-sorbitol, d-mannose, and unsaturated fatty acids, as well as the functional amino acids l-proline and l-lysine. Nanoplastic treatment also resulted in increased activity of succinate dehydrogenase, a key component of energy metabolism, and increased contents of intermediate metabolites or products of energy metabolism, such as adenosine monophosphate, adenosine, guanosine, creatine, and thiamine. Nanoplastic treatment led to an increase in the abundance of certain advantageous genera of gut bacteria, specifically Phaeobacter and Nautella. The observed adaptive response of triploid Fujian oysters to nanoplastic stress provides valuable insights into the mechanisms underpinning resilience in marine bivalves.

Insoluble Dietary Fiber from Okara Combined with Intermittent Fasting Treatment Synergistically Confers Antiobesity Effects by Regulating Gut Microbiota and Its Metabolites.

Insoluble dietary fiber (IDF) was recently revealed to have an antiobesity impact. However, the impact and potential mechanism of high-purity IDF derived from okara (HPSIDF) on obesity caused by a high-fat diet (HFD) remain unclear. Except for dietary supplementation, intermittent fasting (IF) has attracted extensive interest as a new dietary strategy against obesity. Thus, we hypothesize that HPSIDF combined with IF treatment may be more effective in preventing obesity. In this study, HPSIDF combined with IF treatment synergistically alleviated HFD-induced dyslipidemia, impaired glucose homeostasis, systemic inflammation, and fat accumulation. Furthermore, gut microbiota dysbiosis and lowered short-chain fatty acid synthesis were recovered by HPSIDF combined with IF treatment. Meanwhile, metabolomic analysis of feces revealed that HPSIDF combined with IF treatment obviously reversed the alterations of metabolic pathways and differential metabolites induced by HFD, which were linked to the modulations of the gut microbiota. Collectively, our findings indicated that HPSIDF combined with IF treatment has great potential to substantially enhance antiobesity efficacy by modulating the gut microbiota and its metabolites.

Longitudinal assessment of bleomycin-induced pulmonary fibrosis by evaluating TGF-β1/Smad2, Nrf2 signaling and metabolomic analysis in mice

IntroductionPulmonary fibrosis (PF) is characterized by an increase in collagen synthesis and deposition of extracellular matrix. Several factors, including transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog family proteins (Smad), and alpha-smooth muscle actin (α-SMA) trigger extracellular matrix (ECM) accumulation, fibroblast to myofibroblasts conversion, and epithelial-to-mesenchymal-transition (EMT) leading to PF. However, the role of cellular defense mechanisms such as the role of nuclear factor erythroid 2–related factor 2 (Nrf2) signaling during the onset and progression of PF is not understood completely. AimThe present study aims to analyze the involvement of TGF-β1/Smad signaling, and Nrf2 in the EMT and metabolic alterations that promote fibrosis in a time-dependent manner using bleomycin (BLM)-induced PF model in C57BL/6 mice. Key findingsHistopathological studies revealed loss of lung architecture and increased collagen deposition in BLM-exposed mice. BLM upregulated TGF-β1/Smad signaling and α-SMA at all time-points. The gradual increase in the accumulation of α-SMA and collagen implied the progression of PF. BLM exposure raises Nrf2 throughout each specified time-point, which suggests that Nrf2 activation might be responsible for TGF-β1-induced EMT and the development of PF. Further, metabolomic studies linked the development of PF to alterations in metabolic pathways. The pentose phosphate pathway (PPP) was consistently enriched across all the time-points. Additionally, alterations in 22 commonly enriched pathways, associated with fatty acid (FA) and amino acid metabolism were observed in 30- and 60-days. SignificanceThis study elucidates the association of TGF-β1/Smad and Nrf2 signaling in the EMT and metabolic alterations associated with the etiology and progression of PF.