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

Copper boosts the biostimulant activity of a vegetal-derived protein hydrolysate in basil: morpho-physiological and metabolomics insights

Mon, 11/09/2023 - 12:00
Front Plant Sci. 2023 Aug 24;14:1235686. doi: 10.3389/fpls.2023.1235686. eCollection 2023.ABSTRACTIn addition to be used as a plant protection agent, copper (Cu) is also an essential micronutrient for plant growth and development. The bioavailability of Cu in agricultural systems can be limited due to its specific physical-chemical characteristics, leading to imbalances in plant production. To address this issue, an experimental trial was conducted on Genovese basil (Ocimum basilicum L.) in protected conditions to comparatively evaluate the effects of a vegetable protein hydrolysate (VPH), free Cu and Cu complexed with peptides and amino acids of vegetal origin (Cu and Cu-VPH, respectively), and a combination of VPH and Cu-VPH (VPH+Cu-VPH). The study showed that the combined application of VPH+Cu-VPH led to a significant average increase of 16.3% in fresh yield compared to the untreated Control and Cu treatment. This finding was supported by an improved photosynthetic performance in ACO2 (+29%) and Fv/Fm (+7%). Furthermore, mineral analysis using ICP OES demonstrated that Cu and Cu-VPH treatments determined, on average, a 15.1-, 16.9-, and 1.9-fold increase in Cu in plant tissues compared to control, VPH, and VPH+Cu-VPH treatments, respectively. However, the VPH+Cu-VPH treatment induced the highest contents of the other analyzed ions, except for P. In particular, Mg, Mn, Ca, and Fe, which take part in the constitution of chlorophylls, water splitting system, and photosynthetic electron transport chain, increased by 23%, 21%, 25%, and 32% compared to respective controls. Indeed, this improved the photosynthetic efficiency and the carboxylation capacity of the plants, and consequently, the physiological and productive performance of Genovese basil, compared to all other treatments and control. Consistently, the untargeted metabolomics also pointed out a distinctive modulation of phytochemical signatures as a function of the treatment. An accumulation of alkaloids, terpenoids, and phenylpropanoids was observed following Cu treatment, suggesting an oxidative imbalance upon metal exposure. In contrast, a mitigation of oxidative stress was highlighted in Cu-VPH and VPH+Cu-VPH, where the treatments reduced stress-related metabolites. Overall, these results highlight an interaction between Cu and VPH, hence paving the way towards the combined use of Cu and biostimulants to optimize agronomic interventions.PMID:37692443 | PMC:PMC10484225 | DOI:10.3389/fpls.2023.1235686

<em>Trichoderma</em> spp.-mediated mitigation of heat, drought, and their combination on the Arabidopsis thaliana holobiont: a metabolomics and metabarcoding approach

Mon, 11/09/2023 - 12:00
Front Plant Sci. 2023 Aug 21;14:1190304. doi: 10.3389/fpls.2023.1190304. eCollection 2023.ABSTRACTINTRODUCTION: The use of substances to increase productivity and resource use efficiency is now essential to face the challenge of feeding the rising global population with the less environmental impact on the ecosystems. Trichoderma-based products have been used as biopesticides, to inhibit pathogenic microorganisms, and as biostimulants for crop growth, nutrient uptake promotion, and resistance to abiotic stresses.METHODS: In this work, plant metabolomics combined with roots and rhizosphere bacterial metabarcoding were exploited to inspect the performance of Trichoderma spp. biostimulants on Arabidopsis thaliana under drought, heat and their combination and its impact on plant holobiont.RESULTS AND DISCUSSION: An overall modulation of N-containing compounds, phenylpropanoids, terpenes and hormones could be pointed out by metabolomics. Moreover, metabarcoding outlined an impact on alpha and beta-diversity with an abundance of Proteobacteria, Pseudomonadales, Burkholderiales, Enterobacteriales and Azospirillales. A holobiont approach was applied as an integrated analytical strategy to resolve the coordinated and complex dynamic interactions between the plant and its rhizosphere bacteria using Arabidopsis thaliana as a model host species.PMID:37692426 | PMC:PMC10484583 | DOI:10.3389/fpls.2023.1190304

Editorial: Metabolomics: a tool to understand plant protection against biotic and abiotic stresses

Mon, 11/09/2023 - 12:00
Front Plant Sci. 2023 Aug 24;14:1274405. doi: 10.3389/fpls.2023.1274405. eCollection 2023.NO ABSTRACTPMID:37692415 | PMC:PMC10484605 | DOI:10.3389/fpls.2023.1274405

Intestinal acetic acid regulates the synthesis of sex pheromones in captive giant pandas

Mon, 11/09/2023 - 12:00
Front Microbiol. 2023 Aug 25;14:1234676. doi: 10.3389/fmicb.2023.1234676. eCollection 2023.ABSTRACTAs a typical solitary animal, adult giant pandas rely on chemical signals (sex pheromones) to transmit reproductive information during oestrous. Although researchers have confirmed that the gut microbiota is related to the emission and reception of sex pheromones, there is no clear correlation between the gut microbes and the synthesis of sex pheromone of giant pandas, that is, which gut microbes and microbial metabolites are participate in the synthesis of giant panda's sex pheromone. As a mirror of gut microbiota, fecal microbiota can reflect the composition of gut microbiota and its interaction with host to some extent. The purpose of this study is to explore how the gut microbes affect the synthesis of sex pheromones in captive giant pandas by combining analysis of the fecal microbiome and metabolomics. The results of correlation and microbial function analysis show that intestinal microorganisms such as Veillonellaceae and Lactobacillilaceae are associated with the synthesis of short chain fatty acid (acetic acid) and volatile ester metabolites, such as 1-butanol, 3-methyl, acetate, acetic acid, hexyl ester and 3-hexen-1-ol, acetate, (Z). In summary, based on this study, we believe that volatile metabolites such as fecal acetate participate in the process of mate preference of captive giant pandas and affect their expression of natural mating behavior. The possible mechanism is that the gut microbes can promote the synthesis of key chemical signaling substances in perianal glands through mediated intermediate fecal metabolites, thus affecting the normal information exchange between giant pandas individuals. The results of this study have greatly enriched our understanding of gut microbes regulating the synthesis of sex pheromones in giant pandas.PMID:37692393 | PMC:PMC10485365 | DOI:10.3389/fmicb.2023.1234676

Investigating the antidepressant effect of Ziyan green tea on chronic unpredictable mild stress mice through fecal metabolomics

Mon, 11/09/2023 - 12:00
Front Microbiol. 2023 Aug 24;14:1256142. doi: 10.3389/fmicb.2023.1256142. eCollection 2023.ABSTRACTINTRODUCTION: Some studies have shown the effectiveness of tea in reducing depression. Gut flora dysfunction is strongly associated with depression. The mechanism by which Ziyan green tea ameliorates depression is not clear.METHODS: In this study, we examined the impact of Ziyan green tea on mice exhibiting symptoms similar to depression. We specifically focused on the role of intestinal flora and its metabolites. We first established a chronic unpredictable mild stress (CUMS) mouse model to induce depressive symptoms and conducted behavioural tests, biochemical tests, and pathological tissue analysis. We also investigated gut microbiota changes by 16S rRNA sequencing and measured faecal metabolites in mice using UHPLC-MS/MS.RESULTS: The results showed that Ziyan green tea intervention improved depression-like behaviour, neurobiochemical factors, and reduced levels of pro-inflammatory factors in CUMS mice. Spearman's correlation analysis showed that different microbial communities (Corynebacterium, Faecalibaculum, Enterorhabdus, Desulfovibrio) correlation with differential metabolites (Cholic acid, Deoxycholic acid, etc.) and depression-related biochemical indicators (5-HT, DA, BDNF, IL-6, and TNF-α).DISCUSSION: In conclusion, our findings suggest that both low and high-dose interventions of Ziyan green tea have positive preventive effects on CUMS mice without dose dependence, partly because they mainly affect intestinal Purine Metabolism, Bile Acid Biosynthesis and Cysteine Metabolism in CUMS mice, thus stimulating brain 5-HT, DA and BDNF, and decreasing the inflammatory factors IL-6, TNF-α, activate the composition of intestinal flora, improve the intestinal flora environment and thus promote the production of intestinal metabolites, which can be used for depression treatment. It is suggested that Ziyan green tea may achieve an antidepressant effect through the gut-microbiota-brain axis.PMID:37692389 | PMC:PMC10483239 | DOI:10.3389/fmicb.2023.1256142

Angiotensin II modulates THP-1-like macrophage phenotype and inflammatory signatures via angiotensin II type 1 receptor

Mon, 11/09/2023 - 12:00
Front Cardiovasc Med. 2023 Aug 25;10:1129704. doi: 10.3389/fcvm.2023.1129704. eCollection 2023.ABSTRACTAngiotensin II (Ang II) is a major component of the renin-angiotensin or renin-angiotensin-aldosterone system, which is the main element found to be involved in cardiopathology. Recently, long-term metabolomics studies have linked high levels of angiotensin plasma to inflammatory conditions such as coronary heart disease, obesity, and type 2 diabetes. Monocyte/macrophage cellular function and phenotype orchestrate the inflammatory response in various pathological conditions, most notably cardiometabolic disease. An activation of the Ang II system is usually associated with inflammation and cardiovascular disease; however, the direct effect on monocyte/macrophages has still not been well elucidated. Herein, we have evaluated the cellular effects of Ang II on THP-1-derived macrophages. Ang II stimulated the expression of markers involved in monocyte/macrophage cell differentiation (e.g., CD116), as well as adhesion, cell-cell interaction, chemotaxis, and phagocytosis (CD15, CD44, CD33, and CD49F). Yet, Ang II increased the expression of proinflammatory markers (HLA-DR, TNF-α, CD64, CD11c, and CD38) and decreased CD206 (mannose receptor), an M2 marker. Moreover, Ang II induced cytosolic calcium overload, increased reactive oxygen species, and arrested cells in the G1 phase. Most of these effects were induced via the angiotensin II type 1 receptor (AT1R). Collectively, our results provide new evidence in support of the effect of Ang II in inflammation associated with cardiometabolic diseases.PMID:37692050 | PMC:PMC10485254 | DOI:10.3389/fcvm.2023.1129704

The role of the symbiotic microecosystem in cancer: gut microbiota, metabolome, and host immunome

Mon, 11/09/2023 - 12:00
Front Immunol. 2023 Aug 24;14:1235827. doi: 10.3389/fimmu.2023.1235827. eCollection 2023.ABSTRACTThe gut microbiota is not just a simple nutritional symbiosis that parasitizes the host; it is a complex and dynamic ecosystem that coevolves actively with the host and is involved in a variety of biological activities such as circadian rhythm regulation, energy metabolism, and immune response. The development of the immune system and immunological functions are significantly influenced by the interaction between the host and the microbiota. The interactions between gut microbiota and cancer are of a complex nature. The critical role that the gut microbiota plays in tumor occurrence, progression, and treatment is not clear despite the already done research. The development of precision medicine and cancer immunotherapy further emphasizes the importance and significance of the question of how the microbiota takes part in cancer development, progression, and treatment. This review summarizes recent literature on the relationship between the gut microbiome and cancer immunology. The findings suggest the existence of a "symbiotic microecosystem" formed by gut microbiota, metabolome, and host immunome that is fundamental for the pathogenesis analysis and the development of therapeutic strategies for cancer.PMID:37691931 | PMC:PMC10484231 | DOI:10.3389/fimmu.2023.1235827

Inceptor facilitates acrosomal vesicle formation in spermatids and is required for male fertility

Mon, 11/09/2023 - 12:00
Front Cell Dev Biol. 2023 Aug 24;11:1240039. doi: 10.3389/fcell.2023.1240039. eCollection 2023.ABSTRACTSpermatogenesis is a crucial biological process that enables the production of functional sperm, allowing for successful reproduction. Proper germ cell differentiation and maturation require tight regulation of hormonal signals, cellular signaling pathways, and cell biological processes. The acrosome is a lysosome-related organelle at the anterior of the sperm head that contains enzymes and receptors essential for egg-sperm recognition and fusion. Even though several factors crucial for acrosome biogenesis have been discovered, the precise molecular mechanism of pro-acrosomal vesicle formation and fusion is not yet known. In this study, we investigated the role of the insulin inhibitory receptor (inceptor) in acrosome formation. Inceptor is a single-pass transmembrane protein with similarities to mannose-6-phosphate receptors (M6PR). Inceptor knockout male mice are infertile due to malformations in the acrosome and defects in the nuclear shape of spermatozoa. We show that inceptor is expressed in early spermatids and mainly localizes to vesicles between the Golgi apparatus and acrosome. Here we show that inceptor is an essential factor in the intracellular transport of trans-Golgi network-derived vesicles which deliver acrosomal cargo in maturing spermatids. The absence of inceptor results in vesicle-fusion defects, acrosomal malformation, and male infertility. These findings support our hypothesis of inceptor as a universal lysosomal or lysosome-related organelle sorting receptor expressed in several secretory tissues.PMID:37691832 | PMC:PMC10483240 | DOI:10.3389/fcell.2023.1240039

Feeding of fish oil and medium-chain triglycerides to canines impacts circulating structural and energetic lipids, endocannabinoids, and non-lipid metabolite profiles

Mon, 11/09/2023 - 12:00
Front Vet Sci. 2023 Aug 24;10:1168703. doi: 10.3389/fvets.2023.1168703. eCollection 2023.ABSTRACTINTRODUCTION: The effect of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides from fish oil (FO), and their combination (FO+MCT) on the serum metabolome of dogs (Canis familiaris) was evaluated.METHODS: Dogs (N = 64) were randomized to either a control food, one with 7% MCT, one with FO (0.18% eicosapentaenoate and 1.3% docosahexaenoate), or one with FO+MCT for 28 days following a 14-day washout period on the control food. Serum metabolites were analyzed via chromatography followed by mass spectrometry.RESULTS: Additive effects of serum metabolites were observed for a number of metabolite classes, including fatty acids, phospholipids, acylated amines including endocannabinoids, alpha-oxidized fatty acids, and methyl donors. Some effects of the addition of FO+MCT were different when the oils were combined compared with when each oil was fed separately, namely for acylcarnitines, omega-oxidized dicarboxylic acids, and amino acids. Several potentially beneficial effects on health were observed, including decreased circulating triglycerides and total cholesterol with the addition of FO (with or without MCT) and decreases in N-acyl taurines with the addition of MCT, FO, or FO+MCT.DISCUSSION: Overall, the results of this study provide a phenotypic characterization of the serum lipidomic response to dietary supplementation of long-chain n3-polyunsaturated and medium-chain saturated fats in canines.PMID:37691632 | PMC:PMC10484482 | DOI:10.3389/fvets.2023.1168703

Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency

Mon, 11/09/2023 - 12:00
Dis Model Mech. 2023 Sep 11:dmm.050114. doi: 10.1242/dmm.050114. Online ahead of print.ABSTRACTCardiomyopathy is often fatal in Friedreich Ataxia (FA). However, FA hearts maintain adequate function until advanced disease stages, suggesting initial adaptation to the loss of frataxin (FXN). Conditional cardiac knockout mouse models of FXN show transcriptional and metabolic profiles of the mitochondrial integrated stress response (ISRmt), which could play an adaptive role. However, ISRmt has not been investigated in models with disease-relevant, partial decrease of FXN. We characterized the heart transcriptomes and metabolomes of three mouse models with varying degrees of FXN depletion, YG8-800, KIKO-700, and FxnG127V. Few metabolites were changed in YG8-800 mice and did not provide a signature of cardiomyopathy or ISRmt. Instead, several metabolites were altered in FxnG127V and KIKO-700 hearts. Transcriptional changes were found in all models, but differentially expressed genes consistent with cardiomyopathy and ISRmt were only identified in FxnG127V hearts. However, these changes were surprisingly mild even at an advanced age (18-months), despite a severe decrease in FXN levels to 1% of WT. These findings indicate that the mouse heart has low reliance on FXN, highlighting the difficulty in modeling genetically relevant FA cardiomyopathy.PMID:37691621 | DOI:10.1242/dmm.050114

Unraveling the role of intra-cellular metabolites in the lactic acid production by novel <em>Bacillus amyloliquefaciens</em> using sugarcane molasses as a substratum

Mon, 11/09/2023 - 12:00
Mol Omics. 2023 Sep 11. doi: 10.1039/d3mo00141e. Online ahead of print.ABSTRACTLactic acid is a versatile, multi-functional organic monomer in various industries, creating worldwide demand. High titer lactic acid production was achieved by novel Bacillus amyloliquefaciens J2V2AA through sugarcane molasses fermentation up to 178 mg mL-1. A metabolomics approach such as combined GC-MS and LC-MS was applied to elucidate the involvement of key metabolites in lactic acid production. The results revealed the participation of 58 known intra-cellular metabolites at various pathways in lactic acid production. Twenty-eight highly up-regulated and down-regulated metabolites were analyzed, and a schematic diagram of a possible lactic acid production pathway was proposed. The produced lactic acid was analyzed through FTIR, UV-Spectrum, and HPLC analysis.PMID:37691617 | DOI:10.1039/d3mo00141e

Defects in microvillus crosslinking sensitize to colitis and inflammatory bowel disease

Mon, 11/09/2023 - 12:00
EMBO Rep. 2023 Sep 11:e57084. doi: 10.15252/embr.202357084. Online ahead of print.ABSTRACTIntestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) links the microvilli and is required for proper brush border organization. Whether microvillus crosslinking is involved in the intestinal barrier function or colitis is currently unknown. We investigate the role of microvillus crosslinking in colitis in mice with deletion of the IMAC component CDHR5. Electron microscopy shows pronounced brush border defects in CDHR5-deficient mice. The defects result in severe mucosal damage after exposure to the colitis-inducing agent DSS. DSS increases the permeability of the mucus layer and brings bacteria in direct contact with the disorganized brush border of CDHR5-deficient mice. This correlates with bacterial invasion into the epithelial cell layer which precedes epithelial apoptosis and inflammation. Single-cell RNA sequencing data of patients with ulcerative colitis reveals downregulation of CDHR5 in enterocytes of diseased areas. Our results provide experimental evidence that a combination of microvillus crosslinking defects with increased permeability of the mucus layer sensitizes to inflammatory bowel disease.PMID:37691494 | DOI:10.15252/embr.202357084

Biomarkers to guide immunomodulatory treatment: where do we stand?

Mon, 11/09/2023 - 12:00
Expert Rev Mol Diagn. 2023 Sep 10. doi: 10.1080/14737159.2023.2258063. Online ahead of print.ABSTRACTINTRODUCTION: This review summarizes current progress in the development of biomarkers to guide immunotherapy in oncology, rheumatology and critical illness.AREAS COVERED: An extensive literature search was performed about biomarkers classifying patients' immune responses to guide immunotherapy in oncology, rheumatology and critical illness. Surface markers, such as programmed death-ligand 1 (PD-L1), genetic biomarkers, such as tumor mutation load, and circulating tumor DNA are biomarkers associated with the effectiveness of immunotherapy in oncology. Genomics, metabolomics and proteomics play a crucial role in selecting the most suitable therapeutic options for rheumatologic patients. Phenotypes and endotypes are a promising approach to detect critically ill patients with hyper- or hypo-inflammation. Sepsis trials using biomarkers such as ferritin, lymphopenia, HLA-DR expression on monocytes and PD-L1 to guide immunotherapy, have been already conducted or are currently ongoing. Immunotherapy in COVID-19 pneumonia, guided by C-reactive protein and soluble urokinase plasminogen activator receptor (suPAR) has improved patient outcomes globally. More research is needed into immunotherapy in other critical conditions.EXPERT OPINION: Targeted immunotherapy has improved outcomes in oncology and rheumatology, paving the way for precision medicine in the critically ill. Transcriptomics will play a crucial role in detecting the most suitable candidates for immunomodulation.PMID:37691280 | DOI:10.1080/14737159.2023.2258063

A Deeply Quiescent Subset of CML LSC Depend on FAO Yet Avoid Deleterious ROS by Suppressing Mitochondrial Complex I

Mon, 11/09/2023 - 12:00
Curr Mol Pharmacol. 2023 Sep 6. doi: 10.2174/1874467217666230906092236. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Disease relapse and therapy resistance remain serious impediments to treating cancer. Leukemia stem cells (LSC) are therapy resistant and the cause of relapse. A state of deep quiescence appears to enable cancer stem cells (CSC) to acquire new somatic mutations essential for disease progression and therapy resistance. Both normal hematopoietic stem cells (HSC) and LSC share many common features, thereby complicating the safe elimination of LSC. A recent study demonstrated that long lived normal oocytes exist without mitochondrial complex I (MC-1), expressing it in a developmentally regulated fashion, thereby mitigating their vulnerability to ROS. Quiescent CSC rely on mitochondrial FAO, without complex I expression, thereby avoiding the generation of damaging ROS, similar to long lived normal human stem cells. A deeper understanding of the biology of therapy resistance is important for the development of optimal strategies to attain complete leukemia cures.METHODS: Here, using scRNA-sequencing and ATAC-seq on primary chronic myelogenous leukemia (CML) patient samples, combined with bioinformatics analyses, we further examine the heterogeneity of a previously characterized in vitro imatinib-selected CD34-CD38- CML LSC population. We utilized a series of functional analyses, including single-cell metabolomic and Seahorse analyses, to validate the existence of the deepest quiescent leukemia initiators (LI) subset.RESULTS: Current study revealed heterogeneity of therapy resistant LSC in CML patients and their existence of two functionally distinct states. The most deeply quiescent LI suppress the expression of MC-1, yet are highly dependent on fatty acid oxidation (FAO) for their metabolic requirements and ATAC-seq demonstrated increased chromatin accessibility in this population, all consistent with an extremely primitive, quiescent stemness transcriptional signature. Importantly, the specific CREB binding protein (CBP)/β-catenin antagonist ICG-001 initiates the differentiation of LSC, including LI, decreases chromatin accessibility with differentiation and increasing expression of MC-1, CD34, CD38 and BCR-ABL1, thereby re-sensitizing them to imatinib.CONCLUSION: We investigated the biological aspects related to LSC heterogeneity in CML patients and demonstrated the ability of specific small molecule CBP/β-catenin antagonists to safely eliminate deeply quiescent therapy resistant CSC. These observations may represent an attractive generalizable therapeutic strategy that could help develop better protocols to eradicate the quiescent LSC population.PMID:37691195 | DOI:10.2174/1874467217666230906092236

Lipidomics of coconut, almond and soybean milks - Comprehensive characterization of triacylglycerol class and comparison with bovine milk

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113147. doi: 10.1016/j.foodres.2023.113147. Epub 2023 Jun 17.ABSTRACTNowadays, plant-based milk consumption, as part of a healthy diet, is continuously increasing. In this paper, for the first time a lipidomic analysis on molecular species of triacylglycerol (TG) fraction of plant-based beverages (almond, soy, coconut) was performed by liquid chromatography quadrupole time-of-flight mass spectrometry. A total of 557 TG molecular species was measured, showing significantly different profiles between milk alternatives, compared with bovine milk. The most abundant TG molecular species were TG 18:1_18:1_18:1 and 18:1_18:1_18:2 for almond, TG 18:2_18:2_18:2 and 16:0_18:2_18:2 for soy, TG 12:0_10:0_12:0 and 12:0_12:0_14:0 for coconut. Unconventional fatty acids were detected in almond and soy. The main TG with ethereal linkage were TG-O 56:2, TG-O 56:4, and TG-O 56:5, while the main oxygenated TG was TG 54:5;1O. A total of 30 molecular species were identified as biomarkers for milk differentiation by principal component analysis, providing an interesting support for milk authentication and detection of adulteration on a larger sampling.PMID:37689910 | DOI:10.1016/j.foodres.2023.113147

Tissue-specific accumulation of DEHP and involvement of endogenous arachidonic acid in DEHP-induced spleen information and injury

Sun, 10/09/2023 - 12:00
Sci Total Environ. 2023 Sep 8:166841. doi: 10.1016/j.scitotenv.2023.166841. Online ahead of print.ABSTRACTThe plasticizer Diethylhexyl phthalate (DEHP), one of the most common contaminants, is widely detected in environmental and biological samples. However, the accumulation of DEHP in tissue and the molecular mechanisms underlying its physiological damage in the spleen of aquatic organisms have not yet been reported. In this study, gas chromatography-mass spectrometry (GC-MS), histology and multi-omics analysis were used to investigate DEHP exposure-induced alterations in transcriptomic profiles and metabolic network of zebrafish model. After exposure to DEHP, higher concentrations of DEHP were found in the intestine, liver and spleen. Anatomical and histological analyses showed that the zebrafish spleen index was significantly increased and inflammatory damage was observed. Increased splenic neutrophil counts indicate inflammation and tissue damage. Transcriptomic filtering showed that 3579 genes were significantly altered. Metabolomic analysis detected 543 differential metabolites. Multi-omics annotation results indicated that arachidonic acid and 12-Hydroperoxyicosatetraenoic acid (HPETE) are involved in the key inflammatory pathway "Inflammatory mediator regulation of TRP channels". This study demonstrated the accumulation characteristics of DEHP in aquatic zebrafish and the mechanisms of inflammation and tissue damage in the spleen which involve endogenous arachidonic acid. This will provide theoretical basis and data support for health risk assessments and tissue damage of DEHP.PMID:37690753 | DOI:10.1016/j.scitotenv.2023.166841

Dynamic fecal microenvironment properties enable predictions and understanding of peripartum blood oxidative status and non-esterified fatty acids in dairy cows

Sun, 10/09/2023 - 12:00
J Dairy Sci. 2023 Sep 8:S0022-0302(23)00619-7. doi: 10.3168/jds.2022-23066. Online ahead of print.ABSTRACTThe transition period in dairy cows is a critical stage and peripartum oxidative status, negative energy balance (NEB) and inflammation are highly prevalent. Fecal microbial metabolism is closely associated with blood oxidative status and nonesterified fatty acids (NEFA) levels. Here, we investigated dynamic changes in total oxidative status markers and NEFA in blood, fecal microbiome and metabolome of 30 dairy cows during transition (-21d, -7d, +7d, +21d relative to calving). Then the Bayesian network and 9 machine learning algorithms were applied to dismantle their relationship. Our results show that the oxidative status indicator (OSI) of -21d, -7d, +7d was higher than +21d (P < 0.001). The plasma concentration of nonesterified fatty acids (NEFA) peaked on +7d (P < 0.001). For fecal microenvironment, a decline in bacterial α diversity was observed at postpartum (P < 0.001) and in bacterial interactions at +7d (P = 0.014). Conversely, microbial metabolites involved in carbohydrate, lipid and energy metabolism increased on +7d (P < 0.05). A correlation analysis revealed that 11 and 10 microbial metabolites contributed to OSI and NEFA variations, respectively (Arc. strength >0.5). The support vector machine (SVM) radial model showed the highest average predictive accuracy (100% and 88.9% in the test and external data sets) for OSI using 1 metabolite and 3 microbiota. SVM radial model also showed the highest average diagnostic accuracy (100% and 91% in the test and external data sets) for NEFA with 2 metabolites and 3 microbiota. Our results reveal a relationship between variation in the fecal microenvironment and indicators of oxidative status, NEB and inflammation, which provide a theoretical basis for the prevention and precise regulation of peripartum oxidative status and NEB.PMID:37690725 | DOI:10.3168/jds.2022-23066

Metabolic signature biomarkers for predicting the recurrence of urological cancers

Sun, 10/09/2023 - 12:00
Clin Chim Acta. 2023 Sep 8:117553. doi: 10.1016/j.cca.2023.117553. Online ahead of print.ABSTRACTA significant number of patients diagnosed with localized urological cancers experience relapse and disease progression after surgery. Hence, molecular markers for patient risk stratification are needed to improve the current management guidelines. This article critically reviews for the first time, to our knowledge, the promise of metabolomics-based approaches to identify metabolic signatures as candidate prognostic biomarkers to predict recurrences at the time of surgery in prostate cancer (PCa), bladder cancer (BCa), and renal cell carcinoma (RCC). Dysregulations in the levels of several tumoral, circulating, and excreted metabolites have been reported in PCa patients experiencing recurrence within 1.5 to 8 years of follow-up. The combination of these metabolic biomarkers with clinical parameters (e.g., pathological T stage, Gleason score) has shown great potential to improve the predictive ability of PCa recurrence. In contrast, predictive biomarkers of recurrence in BCa and RCC have been poorly explored. Overall, this review highlights the great potential of metabolomics in discovering prognostic biomarkers for a more accurate patient risk stratification in urological cancers.PMID:37690663 | DOI:10.1016/j.cca.2023.117553

Akkermansia muciniphila: A potential target and pending issues for oncotherapy

Sun, 10/09/2023 - 12:00
Pharmacol Res. 2023 Sep 8:106916. doi: 10.1016/j.phrs.2023.106916. Online ahead of print.ABSTRACTIn the wake of the development of metagenomic, metabolomic, and metatranscriptomic approaches, the intricate interactions between the host and various microbes are now being progressively understood. Numerous studies have demonstrated evident changes in gut microbiota during the process of a variety of diseases, such as diabetes, obesity, aging, and cancers. Notably, gut microbiota is viewed as a potential source of novel therapeutics. Currently, Next-generation probiotics (NGPs) are gaining popularity as therapeutic agents that alter the gut microbiota and affect cancer development. Akkermansia muciniphila (A. muciniphila), a representative commensal bacterium, has received substantial attention over the past decade as a promising NGP. The components and metabolites of A. muciniphila can directly or indirectly affect tumorigenesis, in particular through its effects on antitumor immunosurveillance, including the stimulation of pattern recognition receptors (PRRs), which also leads to better outcomes in a variety of situations, including the prevention and curation of cancers. In this article, we systematically summarize the role of A. muciniphila in tumorigenesis (involving gastrointestinal and non-gastrointestinal cancers) and in tumor therapy. In particular, we carefully discuss some critical scientific issues that need to be solved for the future using A. muciniphila as a representative beneficial bacterium in tumor treatment, which might provide bright clues and assistance for the application of drugs targeting A. muciniphila in clinical oncotherapy.PMID:37690533 | DOI:10.1016/j.phrs.2023.106916

Adaptation of the AbsoluteIDQ p180 kit to the analysis of metabolites in the human aqueous humor

Sun, 10/09/2023 - 12:00
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Sep 8;1229:123880. doi: 10.1016/j.jchromb.2023.123880. Online ahead of print.ABSTRACTThe aim of this study was to use the commercial kit AbsoluteIDQ p180 (Biocrates) for the quantification of metabolites in aqueous humor (AH), as well as to determine the optimal volume of AH that is necessary to obtain reliable and reproducible results. Different volumes of AH (10 µl, 20 µl, and 30 µl) were tested. Of the 188 metabolites measurable with the Biocrates kit, 69 were detected in AH. Depending on the volume used, 41, 51, and 63 metabolites were measured using 10 µl, 20 µl, and 30 µl of AH, respectively. The repeatability of the measurements improved with increasing AH volume. Considering only those metabolites that were obtained with a CV < 15%, 34 metabolites at 10 µl, 41 at 20 µl, and 44 at 30 µl AH were received. On this basis, it can be concluded that the tested method can be successfully applied to analyze metabolites in the human AH. To achieve the most comprehensive detection range and highest repeatability of measurements, it is recommended to use 30 µl AH.PMID:37690387 | DOI:10.1016/j.jchromb.2023.123880

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