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

Masson pine pollen aqueous extract ameliorates cadmium-induced kidney damage in rats

Mon, 25/12/2023 - 12:00
Front Mol Biosci. 2023 Dec 6;10:1249744. doi: 10.3389/fmolb.2023.1249744. eCollection 2023.ABSTRACTIntroduction: Cadmium (Cd) is a hazardous environmental pollutant present in soil, water, and food. Accumulation of Cd in organisms can cause systematic injury and damage to the kidney. The Masson pine pollen aqueous extract (MPPAE) has attracted increasing attention due to its antioxidant activity and ability to enhance immunity. Methods: In this study, we investigated the potential of MPPAE to protect against Cd-induced kidney damage in rats and the underlying mechanism. The transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, were explored. Results: The concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA) were both significantly altered after treatment with MPPAE. Furthermore, sequencing and analysis of the transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, revealed differential expression of numerous genes and metabolites compared with the untreated control rats. These differentially expressed genes (DEGs) included detoxification-related genes such as cytochrome P450 and the transporter. The differentially expressed metabolites (DEMs) included 4-hydroxybenzoic acid, L-ascorbate, and ciliatine. Conjoint transcriptome and metabolome analysis showed that several DEGs were correlated with DEMs. Conclusion: These preliminary findings indicate the potential of MPPAE for the treatment of toxic metal poisoning.PMID:38143799 | PMC:PMC10748820 | DOI:10.3389/fmolb.2023.1249744

Combined metabolomics and transcriptomics analysis of rats under neuropathic pain and pain-related depression

Mon, 25/12/2023 - 12:00
Front Pharmacol. 2023 Dec 8;14:1320419. doi: 10.3389/fphar.2023.1320419. eCollection 2023.ABSTRACTNeuropathic pain often leads to negative emotions, which in turn can enhance the sensation of pain. This study aimed to investigate the molecular mechanisms mediating neuropathic pain and negative emotions. Chronic constriction injury (CCI) rats were used as model animals and behavioral tests were conducted to assess pain and negative emotions. Then, the rat anterior cingulate cortex (ACC) was analyzed using UPLC-MS/MS and subsequently integrated with our previously published transcriptome data. Metabolomics analysis revealed that 68 differentially expressed metabolites (DEMs) were identified, mainly in amino acid metabolites and fatty acyls. Combined with our previously published transcriptome data, we predicted two genes that potentially exhibited associations with these metabolites, respectively Apolipoprotein L domain containing 1 (Apold1) and WAP four-disulfide core domain 1 (Wfdc1). Taken together, our results indicated that peripheral nerve injury contributing to neuropathic pain and pain-related depression may be associated with these metabolites and genes. This research provides new insights into the molecular regulatory mechanism, which could serve as a reference for the treatment of neuropathic pain and pain-related depression.PMID:38143492 | PMC:PMC10739318 | DOI:10.3389/fphar.2023.1320419

Metagenomic and metabolomic analysis of the effect of bleaching on unsaturated fatty acid synthesis pathways in coral symbionts

Sun, 24/12/2023 - 12:00
Sci Total Environ. 2023 Dec 22:169487. doi: 10.1016/j.scitotenv.2023.169487. Online ahead of print.ABSTRACTUnsaturated fatty acids (UFA) are known to play a vital role in regulating stress resistance and metabolism in corals. Nevertheless, a comprehensive understanding of the microbial and functional composition of the UFA synthesis pathway (UFASP) remains lacking. This study employed metagenome and metabolome to investigate the microbial community, function, and metabolic response of UFASP in reef-building corals inhabiting the Nansha Islands. Our findings revealed significantly higher diversity for the UFASP microbe in bleached corals compared to unbleached corals. Furthermore, principal coordinates analysis (PCoA) and taxonomy assessments exhibited notable distinctions in the microbe between the two coral states. Notably, the dominant microorganisms involved in UFASP were Dinophyceae, Sordariomycetes, Ulvophyceae, and Chlorophyceae. Bleaching resulted in a considerable increase in fungal abundance within coral symbionts. A total of 12 KEGG Orthology (KO) were identified in UFASP, with PCoA analysis indicating significant differences in their abundance between bleached and unbleached corals. UFASP's beta-Oxidation module exhibited reduced abundance in bleached corals. Contribution analysis highlighted the participation of Symbiodiniaceae, Ascomycota, Chlorophyta, Proteobacteria, and Actinobacteria in UFASP. Notably, Symbiodiniaceae and Ascomycota were the major contributors to two UFASP modules, with the latter displaying greater involvement in bleached corals. Furthermore, significant differences in n3 and n6-family metabolites were observed between bleached and unbleached corals. Notably, bleaching induced a reduction in metabolites of Symbiodiniaceae, while an increase in the multiple UFAs abundance was detected in bleached corals. These findings suggest that bleaching-induced alterations coral symbionts composition directly impact the functionality of UFASP, ultimately affecting the corals' capacity to adapt to stress.PMID:38142991 | DOI:10.1016/j.scitotenv.2023.169487

Dietary fibre confers therapeutic effects in a preclinical model of Huntington's disease

Sun, 24/12/2023 - 12:00
Brain Behav Immun. 2023 Dec 22:S0889-1591(23)00405-1. doi: 10.1016/j.bbi.2023.12.023. Online ahead of print.ABSTRACTHuntington's disease (HD) is a neurodegenerative disorder involving psychiatric, cognitive, and motor deficits, as well as peripheral symptoms, including gastrointestinal dysfunction. The R6/1 HD mouse model expresses a mutant human huntingtin transgene and has been shown to provide an accurate disease model. Recent evidence of gut microbiome disruption was shown in preclinical and clinical HD. Therefore, we aimed to assess the potential role of gut microbial modulation in the treatment of HD. The R6/1 HD mice and wild-type littermate controls were randomised to receive diets containing different amounts of fibre: high-fibre (10 % fibre), control (5 % fibre), or zero-fibre (0 % fibre), from 6 to 20 weeks of age. We characterized the onset and progression of motor, cognitive and affective deficits as well as gastrointestinal function and gut morphological changes. Faeces were collected for gut microbiome profiling using 16S rRNA sequencing at 14 and 20 weeks of age. When compared to the control diet, high-fibre diet improved the performance of HD mice in behavioral tests of cognitive and affective function, as well as the gastrointestinal function of both HD and wild-type mice. While the diets changed the beta diversity of wild-type mice, no statistical significance was observed at 14 or 20 weeks of age within the HD group. Analysis of composition of microbiomes (ANCOM) models were performed to evaluate microbiota composition, which identified differences, including a decreased relative abundance of the phyla Actinobacteriota, Campylobacterota and Proteobacteria and an increased relative abundance of the families Bacteroidaceae, Oscillospiraceae and Ruminococcaceae in HD mice when compared to wild-type after receiving high-fibre diet. PICRUSt2 revealed that high-fibre diet also decreased potentially pathogenic functional pathways in HD. In conclusion, high-fibre intake was effective in enhancing gastrointestinal function, cognition and affective behaviors in HD mice. These findings indicate that dietary fibre interventions may have therapeutic potential in Huntington's disease to delay clinical onset, and have implications for related disorders exhibiting dysfunction of the gut-brain axis.PMID:38142919 | DOI:10.1016/j.bbi.2023.12.023

Adenine is an anti-inflammatory metabolite found to be more abundant in M-CSF over GM-CSF-differentiated human macrophages

Sun, 24/12/2023 - 12:00
Immunol Lett. 2023 Dec 22:S0165-2478(23)00204-3. doi: 10.1016/j.imlet.2023.12.003. Online ahead of print.ABSTRACTImmunometabolism has been unveiled in the last decade to play a major role in controlling macrophage metabolism and inflammation. There has been a constant effort to understand the immunomodulating properties of regulated metabolites during inflammation with the aim of controlling and re-wiring aberrant macrophages in inflammatory diseases. M-CSF and GM-CSF-differentiated macrophages play a key role in mounting successful innate immune responses. When a resolution phase is not achieved however, GM-CSF macrophages contribute substantially more towards an adverse inflammatory milieu than M-CSF macrophages, consequently driving disease progression. Whether there are specific immunometabolites that determine the homeostatic or inflammatory nature of M-CSF and GM-CSF-differentiated macrophages is still unknown. As such, we performed metabolomics analysis on LPS and IL-4-stimulated M-CSF and GM-CSF-differentiated human macrophages to identify differentially accumulating metabolites. Adenine was distinguished as a metabolite significantly higher in M-CSF-differentiated macrophages after both LPS or IL-4 stimulation. Human macrophages treated with adenine before LPS stimulation showed a reduction in inflammatory gene expression, cytokine secretion and surface marker expression. Adenine caused macrophages to become more quiescent by lowering glycolysis and OXPHOS which resulted in reduced ATP production. Moreover, typical metabolite changes seen during LPS-induced macrophage metabolic reprogramming were absent in the presence of adenine. Phosphorylation of metabolic signaling proteins AMPK, p38 MAPK and AKT were not responsible for the suppressed metabolic activity of adenine-treated macrophages. Altogether, in this study we highlight the immunomodulating capacity of adenine in human macrophages and its function in driving cellular quiescence.PMID:38142781 | DOI:10.1016/j.imlet.2023.12.003

A machine learning analysis of "big" metabolomics data for classifying depression: model development and validation

Sun, 24/12/2023 - 12:00
Biol Psychiatry. 2023 Dec 22:S0006-3223(23)01792-4. doi: 10.1016/j.biopsych.2023.12.015. Online ahead of print.ABSTRACTBACKGROUND: There have been many metabolomics studies of depression, but these have been limited by their scale. A comprehensive in silico analysis of global metabolite levels in large populations could provide robust insights into the pathological mechanisms underlying depression and candidate clinical biomarkers.METHODS: Depression-associated metabolomics was studied in two datasets from the UK Biobank database: participants with lifetime depression (n=123,459) and those with current depression (n=94,921). The Whitehall II cohort (n=4,744) was used for external validation. CatBoost machine learning was used for modeling, and Shapley Additive Explanations were used to interpret the model. Five-fold cross-validation was used to validate model performance, training the model on three of the five sets with the remaining two for validation and testing, respectively. The diagnostic performance was assessed using area under receiver operating characteristic (AUC) curves.RESULTS: Twenty-four significantly associated metabolic biomarkers were identified in the lifetime depression and current depression datasets and sex-specific analyses, 12 of which overlapped in the two datasets. The addition of metabolic features slightly improved the performance of a diagnostic model using traditional (non-metabolomic) risk factors alone (lifetime depression: AUCs 0.655 versus 0.658 with metabolomics; current depression: AUCs 0.711 versus 0.716 with metabolomics).CONCLUSIONS: The machine learning model identified 24 metabolic biomarkers associated with depression. If validated, metabolic biomarkers may have future clinical applications as supplementary information to guide early and population-based depression detection.PMID:38142718 | DOI:10.1016/j.biopsych.2023.12.015

Response of neuropeptides to hunger signals in teleost

Sun, 24/12/2023 - 12:00
Neuroendocrinology. 2023 Dec 24. doi: 10.1159/000535611. Online ahead of print.ABSTRACTINTRODUCTION: The perception of hunger is a complex physiological process that requires precise coordination between the central and peripheral tissues.METHODS: In this study, tilapia fasted for 24 hours was chosen to establish a hunger model to study the mechanism of homeostasis recovery under the joint regulation of the central nervous system (CNS) and peripheral tissues.RESULTS: The gastric and intestinal contents of tilapia were predominantly depleted after a fasting period of 9 hours and 24 hours, respectively. The serum glucose level significantly decreased at the 9-h and 24-h fasting, respectively, and the glucokinase-dependent glucosensing mechanism in the liver was identified as well as the significant activation of phospho-AMPK. However, fasting for 24 hours did not activate glucosensing mechanisms and AMPK signaling pathways in the hypothalamus. On the other hand, significant reductions were observed in the mRNA levels of the lipid synthesis-related genes fas and accα, and the serum triglyceride levels as well. The mRNA levels of npy, agrp, pomc and cart in the hypothalamus fluctuated during the fasting period without significant differences. With in situ hybridization npy signals upregulated in the ventral zone of posterior periventricular nucleus after 24-hour fasting, while pomc signals enhanced in the lateral tuberal nucleus. Based on the serum metabolomic analysis, the levels of branched-chain amino acids, butyrate and short-chain acylcarnitine decreased while those of medium- and long-chain acylcarnitine increased.CONCLUSION: Fasting for 24 hours resulted in changes in npy and pomc signals within the hypothalamus, triggered the glucosensing mechanism in the liver of tilapia. This study is beneficial for elucidating the response of neuropeptides in the CNS to the changes of nutritional factors when hungry.PMID:38142691 | DOI:10.1159/000535611

Harpagide inhibits the TNF-α-induced inflammatory response in rat articular chondrocytes by the glycolytic pathways for alleviating osteoarthritis

Sun, 24/12/2023 - 12:00
Int Immunopharmacol. 2023 Dec 23;127:111406. doi: 10.1016/j.intimp.2023.111406. Online ahead of print.ABSTRACTOsteoarthritis (OA) causes severe and functional dysfunction due to abnormal inflammation. The objective of this study was to evaluate the effect of Harpagide (HPG) on TNF-α-induced inflammation in vitro and in vivo. The effect of HPG on the proliferation of rat chondrocytes was studied. The anti-inflammatory effect of HPG and its molecular mechanisms were elucidated by qPCR, Western blotting, flow cytometry, metabolome analysis in vitro. In addition, the OA rat model was established, and the effect of HPG on OA was verified in vivo. We revealed 10 μM HPG demonstrated biocompatibility. The results demonstrated that HPG restored the upregulation of MMP-13, COX2, IL-1β and IL-6 induced by TNF-α. Moreover, HPG reversed TNF-α induced degradation of the extracellular matrix of chondrocytes. TNF-α treatment induced down-regulation of the mRNA/protein levels of proliferative markers Bcl2, CDK1 and Cyclin D1 were also recovered. HPG can inhibit TNF-α-induced inflammatory response through glycolytic metabolic pathways. HPG can restore TNF-α-induced upregulation of GRP78/IRE1α, and downregulation of AMPK proteins. In vivo experiments demonstrated that after HPG treatment, the appearance and physiological structure of articular cartilage were more integrated with highly organized chondrocytes and rich cartilage matrix compared with OA group. Finally, the molecular docking of HPG and selected key factors in glycolysis results showed that HPG had good binding potential with PFKM, PFKP, PFKFB3, PKM, HK2, and PFKL. In conclusion, the results shown HPG protects and activates chondrocytes, inhibits TNF-α-induced inflammatory response by glycolysis pathway in rat articular chondrocytes, and plays a role in the treatment of OA.PMID:38142643 | DOI:10.1016/j.intimp.2023.111406

Advanced progress of spatial metabolomics in head and neck cancer research

Sun, 24/12/2023 - 12:00
Neoplasia. 2023 Dec 23;47:100958. doi: 10.1016/j.neo.2023.100958. Online ahead of print.ABSTRACTHead and neck cancer ranks as the sixth most prevalent malignancy, constituting 5 % of all cancer cases. Its inconspicuous onset often leads to advanced stage diagnoses, prompting the need for early detection to enhance patient prognosis. Currently, research into early diagnostic markers relies predominantly on genomics, proteomics, transcriptomics, and other methods, which, unfortunately, necessitate tumor tissue homogenization, resulting in the loss of temporal and spatial information. Emerging as a recent addition to the omics toolkit, spatial metabolomics stands out. This method conducts in situ mass spectrometry analyses on fresh tissue specimens while effectively preserving their spatiotemporal information. The utilization of spatial metabolomics in life science research offers distinct advantages. This article comprehensively reviews the progress of spatial metabolomics in head and neck cancer research, encompassing insights into cancer cell metabolic reprogramming. Various mass spectrometry imaging techniques, such as secondary ion mass spectrometry, stroma-assisted laser desorption/ionization, and desorption electrospray ionization, enable in situ metabolite analysis for head and neck cancer. Finally, significant emphasis is placed on the application of presently available techniques for early diagnosis, margin assessment, and prognosis of head and neck cancer.PMID:38142528 | DOI:10.1016/j.neo.2023.100958

Carboxymethyl chitosan and polycaprolactone-based rapid in-situ packaging for fruit preservation by solution blow spinning

Sat, 23/12/2023 - 12:00
Carbohydr Polym. 2024 Feb 15;326:121636. doi: 10.1016/j.carbpol.2023.121636. Epub 2023 Nov 23.ABSTRACTNanofiber packaging has not yet gained practical application in fruit preservation because of some limitations, such as low production rate and utilization, and failure due to poor adhesion to the fruit. Herein, to solve this issue, a novel fruit packaging method based on solution blow spinning (SBS), called in-situ packaging, was pioneered. Specifically, carboxymethyl chitosan (CMCH) and polycaprolactone (PCL) were chosen as substrate materials and cherry tomatoes were selected as demonstration subjects. CMCH/PCL nanofibers were deposited directly onto the surface of cherry tomatoes by SBS, forming a tightly adherent and stable fiber coating in 8 min. Also, this in-situ packaging could be easily peeled off by hand. The in-situ packaging was an excellent carrier for active substances and was effective in inhibiting gray mold on cherry tomatoes. The in-situ packaging film formed a barrier on the surface of cherry tomatoes to limit moisture penetration, resulting in reduced respiration of fruits, which led to reduced weight and firmness loss. In addition, metabolomics and color analysis revealed that the in-situ packaging delayed ripening of cherry tomatoes after harvest. Overall, the in-situ packaging method developed in the present work provides a new solution for post-harvest fruit preservation.PMID:38142080 | DOI:10.1016/j.carbpol.2023.121636

Targeting Acid Ceramidase enhances antitumor immune response in colorectal cancer

Sat, 23/12/2023 - 12:00
J Adv Res. 2023 Dec 21:S2090-1232(23)00403-4. doi: 10.1016/j.jare.2023.12.013. Online ahead of print.ABSTRACTINTRODUCTION: Acid ceramidase (hereafter referred as ASAH1) is an enzyme in sphingolipid metabolism that converts pro-survival ceramide into sphingosine. ASAH1 has been shown to be overexpressed in certain cancers. However, the role of ASAH1 in colorectal cancer is still remain elusive OBJECTIVE: The present study is aimed to understand how ASAH1 regulates colorectal cancer (CRC) progression and resistance to checkpoint inhibitor therapy.METHODS: Both pharmacological and genetic silencing of ASAH1 was used in the study. In vitro experiments were done on human and mouse CRC cell lines. The in vivo studies were conducted in NOD-SCID and BALB/c mice models. The combination of ASAH1 inhibitor and checkpoint inhibitor was tested using a syngeneic tumor model of CRC. Transcriptomic and metabolomic analyses were done to understand the effect of ASAH1 silencing.RESULTS: ASAH1 is overexpressed in human CRC cases, and silencing the expression resulted in the induction of immunological cell death (ICD) and mitochondrial stress. The ASAH1 inhibitor (LCL-521), either as monotherapy or in combination with an anti-PD-1 antibody, resulted in a reduction of tumors and, through induction of type I and II interferon response, activation of M1 macrophages and T cells, leading to enhanced infiltration of cytotoxic T cells. Our findings supported that the combination of LCL-521 and ICIs, which enhances the antitumor responses, and ASAH1 can be a druggable target in CRC.PMID:38142035 | DOI:10.1016/j.jare.2023.12.013

The SLC38A9-mTOR axis is involved in autophagy in the juvenile yellow catfish (Pelteobagrus fulvidraco) under ammonia stress

Sat, 23/12/2023 - 12:00
Environ Pollut. 2023 Dec 21:123211. doi: 10.1016/j.envpol.2023.123211. Online ahead of print.ABSTRACTThe primary objective of this study was to examine the effect of acute ammonia stress on hepatic physiological alterations in yellow catfish by performing a comprehensive analysis of the metabolome and transcriptome. The present study showed that ammonia stress led to liver metabolic disruption, functional incapacitation, and oxidative damage. Transcriptomic and metabolomic analyses revealed transcriptional and metabolic differences in the liver of yellow catfish under control and high ammonia stress conditions. After 96 h of acute exposure to ammonia, the mRNA levels of 596 liver genes were upregulated, whereas those of 603 genes were downregulated. Enrichment analysis of the differentially expressed genes identified multiple signalling pathways associated with autophagy, including the endocytosis, autophagy-animal, and mammalian target of rapamycin signalling pathways. A total of 186 upregulated and 117 downregulated metabolites, primarily associated with amino acid biosynthesis pathways, were identified. Multi-omics integration revealed the solute carrier family 38 member 9 (SLC38A9)-mammalian target of rapamycin axis as a signalling nexus for amino acid-mediated modulation of autophagy flux, and q-PCR was used to assess the expression of autophagy-related genes (LC3a and sqstm1), revealing an initial inhibition followed by the restoration of autophagic flux during ammonia stress. Subsequent utilisation of arginine as a specific SLC38A9 activator during ammonia stress demonstrated that augmented SLC38A9 expression hindered autophagy, exacerbated ammonia toxicity, and caused a physiological decline (total cholesterol, total triglyceride, acid phosphatase, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels were significantly increased), oxidative stress, and apoptosis. Autophagy activation may be an adaptive mechanism to resist ammonia stress.PMID:38142034 | DOI:10.1016/j.envpol.2023.123211

Comprehensive effects of thiamethoxam from contaminated soil on lettuce growth and metabolism

Sat, 23/12/2023 - 12:00
Environ Pollut. 2023 Dec 21:123186. doi: 10.1016/j.envpol.2023.123186. Online ahead of print.ABSTRACTThe second-generation neonicotinoid thiamethoxam, is prevalent in soils because of its extensive application and persistence. However, the comprehensive effects of thiamethoxam residue in soils on cultivated plants are still poorly understood. This study examined variations of growth state, physiological parameters, antioxidant activity, and metabolites in lettuce after thiamethoxam exposure; the removal effects of different washing procedures were also investigated. The results indicated that thiamethoxam in soils significantly increased the fresh weight, seedling height and chlorophyll content in lettuce, and also altered its lipid, carbohydrate, nucleotide and amino acids composition based on untargeted metabolomics. KEGG pathway analysis uncovered a disruption of lipid pathways in lettuce exposed to both low and high concentrations of thiamethoxam treatments. In addition, the terminal residues of thiamethoxam in lettuce were below the corresponding maximum residue limits stipulated for China. The thiamethoxam removal rates achieved by common washing procedures in lettuce ranged from 26.9 to 42.6%. This study thus promotes the understanding of the potential food safety risk caused by residual thiamethoxam in soils.PMID:38142029 | DOI:10.1016/j.envpol.2023.123186

Exploring applications of non-targeted analysis in the characterization of the prenatal exposome

Sat, 23/12/2023 - 12:00
Sci Total Environ. 2023 Dec 21:169458. doi: 10.1016/j.scitotenv.2023.169458. Online ahead of print.ABSTRACTCapturing the breadth of chemical exposures in utero is critical in understanding their long-term health effects for mother and child. We explored methodological adaptations in a Non-Targeted Analysis (NTA) pipeline and evaluated the effects on chemical annotation and discovery for maternal and infant exposure. We focus on lesser-known/underreported chemicals in maternal and umbilical cord serum analyzed with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The samples were collected from a demographically diverse cohort of 296 maternal-cord pairs (n = 592) recruited in San Francisco Bay area. We developed and evaluated two data processing pipelines, primarily differing by detection frequency cut-off, to extract chemical features from non-targeted analysis (NTA). We annotated the detected chemical features by matching with EPA CompTox Chemicals Dashboard (n = 860,000 chemicals) and Human Metabolome Database (n = 3140 chemicals) and applied a Kendrick Mass Defect filter to detect homologous series. We collected fragmentation spectra (MS/MS) on a subset of serum samples and matched to an experimental MS/MS database within the MS-Dial website and other experimental MS/MS spectra collected from standards in our lab. We annotated ~72 % of the features (total features = 32,197, levels 1-4). We confirmed 22 compounds with analytical standards, tentatively identified 88 compounds with MS/MS spectra, and annotated 4862 exogenous chemicals with an in-house developed annotation algorithm. We detected 36 chemicals that appear to not have been previously reported in human blood and 9 chemicals that were reported in less than five studies. Our findings underline the importance of NTA in the discovery of lesser-known/unreported chemicals important to characterize human exposures.PMID:38142008 | DOI:10.1016/j.scitotenv.2023.169458

Biomonitoring of heavy metals and their phytoremediation by duckweeds: Advances and prospects

Sat, 23/12/2023 - 12:00
Environ Res. 2023 Dec 21:118015. doi: 10.1016/j.envres.2023.118015. Online ahead of print.ABSTRACTHeavy metals (HMs) contamination of water bodies severely threatens human and ecosystem health. There is growing interest in the use of duckweeds for HMs biomonitoring and phytoremediation due to their fast growth, low cultivation costs, and excellent HM uptake efficiency. In this review, we summarize the current state of knowledge on duckweeds and their suitability for HM biomonitoring and phytoremediation. Duckweeds have been used for phytotoxicity assays since the 1930s. Some toxicity tests based on duckweeds have been listed in international guidelines. Duckweeds have also been recognized for their ability to facilitate HM phytoremediation in aquatic environments. Large-scale screening of duckweed germplasm optimized for HM biomonitoring and phytoremediation is still essential. We further discuss the morphological, physiological, and molecular effects of HMs on duckweeds. However, the existing data are clearly insufficient, especially in regard to dissection of the transcriptome, metabolome, proteome responses and molecular mechanisms of duckweeds under HM stresses. We also evaluate the influence of environmental factors, exogenous substances, duckweed community composition, and HM interactions on their HM sensitivity and HM accumulation, which need to be considered in practical application scenarios. Finally, we identify challenges and propose approaches for improving the effectiveness of duckweeds for bioremediation from the aspects of selection of duckweed strain, cultivation optimization, engineered duckweeds. We foresee great promise for duckweeds as phytoremediation agents, providing environmentally safe and economically efficient means for HM removal. However, the primary limiting issue is that so few researchers have recognized the outstanding advantages of duckweeds. We hope that this review can pique the interest and attention of more researchers.PMID:38141920 | DOI:10.1016/j.envres.2023.118015

Molecular profiling of high-level athlete skeletal muscle after acute endurance or resistance exercise - a systems biology approach

Sat, 23/12/2023 - 12:00
Mol Metab. 2023 Dec 21:101857. doi: 10.1016/j.molmet.2023.101857. Online ahead of print.ABSTRACTOBJECTIVE: Long-term high-level exercise training leads to improvements in physical performance and multi-tissue adaptation following changes in molecular pathways. While skeletal muscle baseline differences between exercise-trained and untrained individuals have been previously investigated, it remains unclear how training history influences human multi-omics responses to acute exercise.METHODS: We recruited and extensively characterized 24 individuals categorized as endurance athletes with >15 years of training history, strength athletes or control subjects. Timeseries skeletal muscle biopsies were taken from M. vastus lateralis at three time-points after endurance or resistance exercise was performed and multi-omics molecular analysis performed.RESULTS: Our analyses revealed distinct activation differences of molecular processes such as fatty- and amino acid metabolism and transcription factors such as HIF1A and the MYF-family. We show that endurance athletes have an increased abundance of carnitine-derivates while strength athletes increase specific phospholipid metabolites compared to control subjects. Additionally, for the first time, we show the metabolite sorbitol to be substantially increased with acute exercise. On transcriptional level, we show that acute resistance exercise stimulates more gene expression than acute endurance exercise. This follows a specific pattern, with endurance athletes uniquely down-regulating pathways related to mitochondria, translation and ribosomes. Finally, both forms of exercise training specialize in diverging transcriptional directions, differentiating themselves from the transcriptome of the untrained control group.CONCLUSIONS: We identify a "transcriptional specialization effect" by transcriptional narrowing and intensification, and molecular specialization effects on metabolomic level Additionally, we performed multi-omics network and cluster analysis, providing a novel resource of skeletal muscle transcriptomic and metabolomic profiling in highly trained and untrained individuals.PMID:38141850 | DOI:10.1016/j.molmet.2023.101857

Corrigendum to "Study on the anti-mitochondrial apoptosis mechanism of Erigeron breviscapus injection based on UPLC-Q-TOF-MS metabolomics and molecular docking in rats with cerebral ischemia-reperfusion injury" [J. Ethnopharmacol. 319 (Part 2) (2024)...

Sat, 23/12/2023 - 12:00
J Ethnopharmacol. 2023 Dec 22;322:117596. doi: 10.1016/j.jep.2023.117596. Online ahead of print.NO ABSTRACTPMID:38141517 | DOI:10.1016/j.jep.2023.117596

Red light alleviates Cd toxicity in Egeria densa by modifying carbon-nitrogen metabolism and boosting energy metabolism

Sat, 23/12/2023 - 12:00
Aquat Toxicol. 2023 Dec 13;266:106804. doi: 10.1016/j.aquatox.2023.106804. Online ahead of print.ABSTRACTAmong the various pollutants detected in aquatic ecosystems, cadmium (Cd) is considered as one of the most hazardous. Freshwater macrophytes have been recognized as possible candidates for eliminating Cd from environment. Nevertheless, the impact of light quality on their ability to tolerate Cd toxicity remains unclear, and the underlying mechanisms have yet to be fully elucidated. In this study, we utilized physiological testing and metabolomics to explore the potential mechanisms by which light quality influences the ability of Egeria densa, a significant Cd hyperaccumulator, to withstand Cd toxicity. The study demonstrated that following Cd treatment, E. densa grown under red light exhibited superior photosynthetic efficiency compared to those grown under blue light, as evidenced by significantly increased photosynthetic rate, higher starch content, and greater activity of photosynthetic enzymes. Moreover, metabolomic analyses revealed that under Cd stress, E. densa grown under red light exhibited an enhanced glycolysis for increased energy production. Sucrose metabolism was also improved to generate sufficient sugar including glucose, fructose and mannose for osmotic adjustment. Moreover, under red light, the heightened production of α-ketoglutarate via tricarboxylic acid (TCA) cycle redirected nitrogen flow towards the synthesis of resilient substances such as γ-Aminobutyric Acid (GABA) and methionine. The production of these substances was ∼2.0 and 1.3 times greater than that of treatment with Cd under blue light, thereby improving E. densa's capacity to withstand Cd stress. This study represents the initial investigation into the possible mechanisms by which light quality influences the ability of E. densa to withstand Cd toxicity through regulating CN metabolism. Furthermore, these findings have the potential to improve phytoremediation strategies aimed at reducing Cd pollution.PMID:38141498 | DOI:10.1016/j.aquatox.2023.106804

A comprehensive analysis of hepatopancreas metabolomics and transcriptomics provides insights into the growth of three-year-old crabs (Eriocheir sinensis) under low temperature

Sat, 23/12/2023 - 12:00
Comp Biochem Physiol Part D Genomics Proteomics. 2023 Dec 20;49:101182. doi: 10.1016/j.cbd.2023.101182. Online ahead of print.ABSTRACTLow water temperature is a critical environmental factor limiting the size of cultivated aquatic individuals. However, it has found that a proportion of Eriocheir sinensis cultured in low water temperature with high-altitude can mature into three-year-old crabs, which present larger body size than conventional two-year-old crabs. Based on integrated transcriptomic and metabolomic analysis, the significantly difference focuses on metabolic pathways involving glycine, serine, and threonine metabolism, amino sugar and nucleotide sugar metabolism, cysteine and methionine metabolism, pantothenate and CoA biosynthesis, arginine and proline metabolism, and vitamin digestion and absorption. It revealed that the growth performance of three-year-old crabs is mainly regulated by improving its antioxidant defense to maintain physical fitness, while reducing protein consumption by intensifying energy supplement ability and enhancing the ability to digest and absorb nutrients at low temperature. This study provides new insights on the molecular and metabolic pathways that control E. sinensis growth at high-altitude and low water temperature, laying the theoretical basis for further artificial three-year-old crabs breeding.PMID:38141371 | DOI:10.1016/j.cbd.2023.101182

Selenium - An environmentally friendly micronutrient in agroecosystem in the modern era: An overview of 50-year findings

Sat, 23/12/2023 - 12:00
Ecotoxicol Environ Saf. 2023 Dec 22;270:115832. doi: 10.1016/j.ecoenv.2023.115832. Online ahead of print.ABSTRACTAgricultural productivity is constantly being forced to maintain yield stability to feed the enormously growing world population. However, shrinking arable and nutrient-deprived soil and abiotic and biotic stressor (s) in different magnitudes put additional challenges to achieving global food security. Though well-defined, the concept of macro, micronutrients, and beneficial elements is from a plant nutritional perspective. Among various micronutrients, selenium (Se) is essential in small amounts for the life cycle of organisms, including crops. Selenium has the potential to improve soil health, leading to the improvement of productivity and crop quality. However, Se possesses an immense encouraging phenomenon when supplied within the threshold limit, also having wide variations. The supplementation of Se has exhibited promising outcomes in lessening biotic and abiotic stress in various crops. Besides, bulk form, nano-Se, and biogenic-Se also revealed some merits and limitations. Literature suggests that the possibilities of biogenic-Se in stress alleviation and fortifying foods are encouraging. In this article, apart from adopting a combination of a conventional extensive review of the literature and bibliometric analysis, the authors have assessed the journey of Se in the "soil to spoon" perspective in a diverse agroecosystem to highlight the research gap area. There is no doubt that the time has come to seriously consider the tag of beneficial elements associated with Se, especially in the drastic global climate change era.PMID:38141336 | DOI:10.1016/j.ecoenv.2023.115832

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