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

Fruit beers, beers with or without a co-fermentation step with fruits

Wed, 21/02/2024 - 12:00
Curr Opin Biotechnol. 2024 Feb 20;86:103081. doi: 10.1016/j.copbio.2024.103081. Online ahead of print.ABSTRACTBelgium is known for its traditional lambic beer productions, obtained through spontaneous fermentation and maturation in wooden barrels. Lambic beer is also used to make fruit lambic beers, such as Kriek beer. Despite fruit beer being an old beer type, dating back to the second half of the seventeenth century, no research has been performed on lambic beer-fruit co-fermentation processes. Further, these beers get competition from market-driven, sweet, (fruit-)flavored ones without the co-fermentation step. This paper will first discuss a new, general fruit beer classification, going from sour fruit beers produced through co-fermentation to sweet ones without a co-fermentation step. Second, a state-of-the-art of the scarce literature on the microbiology and metabolomics of lambic beer-fruit co-fermentation processes will be given.PMID:38382326 | DOI:10.1016/j.copbio.2024.103081

Mass spectrometry imaging-based metabolomics highlights spatial metabolic alterations in three types of liver injuries

Wed, 21/02/2024 - 12:00
J Pharm Biomed Anal. 2024 Feb 10;242:116030. doi: 10.1016/j.jpba.2024.116030. Online ahead of print.ABSTRACTLiver's distinctive function renders it highly susceptible to diverse damage sources. Characterizing the metabolic profiles and spatial signatures in different liver injuries is imperative for early diagnosis and etiology-oriented treatment. In this comparative study, we conducted whole-body spatial metabolomics on zebrafish with liver injury induced by ethanol (EtOH), acetaminophen (APAP), and thioacetamide (TAA). The two specific levels, the whole-body and liver-specific metabolic profiles, as well as their regional distributions, were systematically mapped in situ by mass spectrometry imaging, which is distinct from conventional LC-MS and GC-MS methods. We found that liver injury regions exhibited more pronounced metabolic reprogramming than the entire organism, leading to significant alterations in eight fatty acids, three phospholipids, and four low-molecular-weight metabolites. More importantly, fatty acids as well as small molecule metabolites including glutamine, glutamate, taurine and malic acid displayed contrasting changes between alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). In addition, phospholipids, including Lyso PC (16:0) and Lyso PE (18:0), demonstrated notable down-regulation in all damaged liver, whereas PC (34:1) underwent upregulation. This study not only deepens insights into distinct potential biomarkers for liver injuries, but also underscores spatial metabolomics as a powerful tool to elucidate possible pathogenic mechanisms in other metabolic diseases.PMID:38382318 | DOI:10.1016/j.jpba.2024.116030

Metabolomic analysis reveals the biological characteristics of giant congenital melanocytic nevi

Wed, 21/02/2024 - 12:00
J Pharm Biomed Anal. 2024 Feb 18;242:116060. doi: 10.1016/j.jpba.2024.116060. Online ahead of print.ABSTRACTGiant congenital melanocytic nevi (GCMN) is a congenital cutaneous developmental deformity tumor that usually occurs at birth or in the first few weeks after birth, but its pathogenesis is still unclear. In this study, nuclear magnetic resonance-based metabolomics strategy was employed to evaluate the metabolic variations in serum and urine of the GCMN patients in order to understand its underlying biochemical mechanism and provide a potential intervention idea. Twenty-nine metabolites were observed to change significantly in serum and urine metabolomes, which are mainly involved in a variety of metabolic pathways including glyoxylate and dicarboxylate metabolism, TCA cycle and metabolisms of amino acids. The substantial cores of all the disturbed metabolic pathways are related to amino acid metabolism and carbohydrate metabolism and regulate the physiological state of the GCMN patients. Our results provide the physiological basis and physiological responses of GCMN and will be helpful for better understanding the molecular mechanisms of GCMN in future research.PMID:38382316 | DOI:10.1016/j.jpba.2024.116060

UPLC-QTOF-MS based metabolomics unravels the modulatory effect of ginseng water extracts on rats with Qi-deficiency

Wed, 21/02/2024 - 12:00
J Pharm Biomed Anal. 2024 Feb 7;242:116019. doi: 10.1016/j.jpba.2024.116019. Online ahead of print.ABSTRACTGinseng is commonly used as a nutritional supplement and daily wellness product due to its ability to invigorate qi. As a result, individuals with Qi-deficiency often use ginseng as a health supplement. Ginsenosides and polysaccharides are the primary components of ginseng. However, the therapeutic effects and mechanisms of action of these components in Qi-deficiency remain unclear. This study aimed to determine the modulatory effects and mechanisms of ginseng water extract, ginsenosides, and ginseng polysaccharides in a rat model of Qi-deficiency using metabolomics and network analysis. The rat model of Qi-deficiency was established via swimming fatigue and a restricted diet. Oral administration of different ginseng water extracts for 30 days primarily alleviated oxidative stress and disrupted energy metabolism and immune response dysfunction caused by Qi-deficiency in rats. Ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for untargeted serum metabolomic analysis. Based on the analysis results, the active constituents of ginseng significantly reversed the changes in serum biomarkers related to Qi-deficiency in rats, particularly energy, amino acid, and unsaturated fatty acid metabolism. Furthermore, analysis of the metabolite-gene network suggested that the anti-Qi-deficiency effects of the ginseng components were mainly associated with toll-like receptor (TLR) signaling and inflammatory response. Additional verification revealed that treatment with the ginseng components effectively reduced the inflammatory response and activation of the myocardial TLR4/NF-κB pathway induced by Qi-deficiency, especially the ginseng water extracts. Therefore, ginseng could be an effective preventive measure against the progression of Qi-deficiency by regulating metabolic and inflammatory responses.PMID:38382315 | DOI:10.1016/j.jpba.2024.116019

Benchtop volatilomics supercharged: How machine learning based design of experiment helps optimizing untargeted GC-IMS gas phase metabolomics

Wed, 21/02/2024 - 12:00
Talanta. 2024 Feb 14;272:125788. doi: 10.1016/j.talanta.2024.125788. Online ahead of print.ABSTRACTGas chromatography-ion mobility spectrometry (GC-IMS) plays a significant role in both targeted and non-targeted analyses. However, the non-linear behavior of IMS and its complex ion chemistry pose challenges for finding optimal experimental conditions using existing methodologies. To address these issues, integrating machine learning (ML) strategies offers a promising approach. In this study, we propose a hybrid strategy, combining design of experiment (DOE) and machine learning (ML) for optimizing GC-IMS conditions in non-targeted volatilomic/flavoromic analysis, with saffron volatiles as a case study. To begin, a rotatable circumscribed central composite design (CCD) is used to define five influential GC-IMS factors of sample amount, headspace temperature, incubation time, injection volume, and split ratio. Subsequently, two ML models are utilized: multiple linear regression (MLR) as a linear model and Bayesian regularized-artificial neural network (BR-ANN) as a nonlinear model. These models are employed to predict the response variables of total peak areas (PAs) and the number of detected peaks (PNs) in GC-IMS. The findings show that there is a direct correlation between the factors in GC-IMS and the PNs, suggesting that MLR is a suitable approach for building a model in this scenario. However, the PAs exhibit nonlinear behavior, suggesting that BR-ANN is better suitable to capture this complexity. Notably, Derringer's desirability function is utilized to integrate the PAs and PNs, and in this scenario, MLR demonstrates satisfactory performance in modeling the GC-IMS factors.PMID:38382301 | DOI:10.1016/j.talanta.2024.125788

Schisandrin A alleviates renal fibrosis by inhibiting PKCβ and oxidative stress

Wed, 21/02/2024 - 12:00
Phytomedicine. 2024 Jan 17;126:155372. doi: 10.1016/j.phymed.2024.155372. Online ahead of print.ABSTRACTBACKGROUND: Renal fibrosis is a common pathway that drives the advancement of numerous kidney maladies towards end-stage kidney disease (ESKD). Suppressing renal fibrosis holds paramount clinical importance in forestalling or retarding the transition of chronic kidney diseases (CKD) to renal failure. Schisandrin A (Sch A) possesses renoprotective effect in acute kidney injury (AKI), but its effects on renal fibrosis and underlying mechanism(s) have not been studied.STUDY DESIGN: Serum biochemical analysis, histological staining, and expression levels of related proteins were used to assess the effect of PKCβ knockdown on renal fibrosis progression. Untargeted metabolomics was used to assess the effect of PKCβ knockdown on serum metabolites. Unilateral Ureteral Obstruction (UUO) model and TGF-β induced HK-2 cells and NIH-3T3 cells were used to evaluate the effect of Schisandrin A (Sch A) on renal fibrosis. PKCβ overexpressed NIH-3T3 cells were used to verify the possible mechanism of Sch A.RESULTS: PKCβ was upregulated in the UUO model. Knockdown of PKCβ mitigated the progression of renal fibrosis by ameliorating perturbations in serum metabolites and curbing oxidative stress. Sch A alleviated renal fibrosis by downregulating the expression of PKCβ in kidney. Treatment with Sch A significantly attenuated the upregulated proteins levels of FN, COL-I, PKCβ, Vimentin and α-SMA in UUO mice. Moreover, Sch A exhibited a beneficial impact on markers associated with oxidative stress, including MDA, SOD, and GSH-Px. Overexpression of PKCβ was found to counteract the renoprotective efficacy of Sch A in vitro.CONCLUSION: Sch A alleviates renal fibrosis by inhibiting PKCβ and attenuating oxidative stress.PMID:38382281 | DOI:10.1016/j.phymed.2024.155372

Artesunate improves glucose and lipid metabolism in db/db mice by regulating the metabolic profile and the MAPK/PI3K/Akt signalling pathway

Wed, 21/02/2024 - 12:00
Phytomedicine. 2024 Jan 30;126:155382. doi: 10.1016/j.phymed.2024.155382. Online ahead of print.ABSTRACTBACKGROUND: Diabetes is a metabolic disorder characterized by chronic hyperglycaemia. Chronic metabolic abnormalities and long-term hyperglycaemia may result in a wide range of acute and chronic consequences. Previous studies have demonstrated that artesunate(ART) has antidiabetic, anti-inflammatory, antiatherosclerotic, and other beneficial effects, but the specific regulatory mechanism is not completely clear.AIM: This study investigated the effects of ART on metabolic disorders in type 2 diabetes mellitus (T2DM) model db/db mice and explored the underlying mechanisms involved.METHODS: C57BL/KsJ-db/db mice were used to identify the targets and molecular mechanism of ART. Metabolomic methods were used to evaluate the efficacy of ART in improving T2DM-related metabolic disorders. Network pharmacology and transcriptomic sequencing were used to analyse the targets and pathways of ART in T2DM. Finally, molecular biology experiments were performed to verify the key targets and pathways selected by network pharmacology and transcriptomic analyses.RESULTS: After a 7-week ART intervention (160 mg/kg), the glucose and lipid metabolism levels of the db/db mice improved. Additionally, the oxidative stress indices, namely, the MDA and SOD levels, significantly improved (p<0.01). Linoleic acid and glycerophospholipid metabolism, amino acid metabolism, bile acid synthesis, and purine metabolism disorders in db/db mice were partially corrected after ART treatment. Network pharmacology analysis identified important targets of ART for the treatment of metabolic disorders in T2DM . These targets are involved in key signalling pathways, including the highest scores observed for the PI3K/Akt signalling pathway. Transcriptomic analysis revealed that ART could activate the MAPK signalling pathway and two key gene targets, HGK and GADD45. Immunoblotting revealed that ART increases p-PI3K, p-AKT, Glut2, and IRS1 protein expression and suppresses the phosphorylation of p38, ERK1/2, and JNK, returning HGK and GADD45 to their preartesunate levels.CONCLUSION: Treatment of db/db mice with 160 mg/kg ART for 7 weeks significantly reduced fasting blood glucose and lipid levels. It also improved metabolic imbalances in amino acids, lipids, purines, and bile acids, thereby improving metabolic disorders. These effects are achieved by activating the PI3K/AKT pathway and inhibiting the MAPK pathway, thus demonstrating the efficacy of the drug.PMID:38382280 | DOI:10.1016/j.phymed.2024.155382

Study on the potential mechanism of Qingxin Lianzi Yin Decoction on renoprotection in db/db mice via network pharmacology and metabolomics

Wed, 21/02/2024 - 12:00
Phytomedicine. 2023 Nov 15;126:155222. doi: 10.1016/j.phymed.2023.155222. Online ahead of print.ABSTRACTBACKGROUND: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed.PURPOSE: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies.METHODS: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-β-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results.RESULTS: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine.CONCLUSION: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.PMID:38382279 | DOI:10.1016/j.phymed.2023.155222

Integrated application of transcriptomics and metabolomics provides insight into the mechanism of Eimeria tenella resistance to maduramycin

Wed, 21/02/2024 - 12:00
Int J Parasitol Drugs Drug Resist. 2024 Feb 15;24:100526. doi: 10.1016/j.ijpddr.2024.100526. Online ahead of print.ABSTRACTAvian coccidiosis, caused by Eimeria parasites, continues to devastate the poultry industry and results in significant economic losses. Ionophore coccidiostats, such as maduramycin and monensin, are widely used for prophylaxis of coccidiosis in poultry. Nevertheless, their efficacy has been challenged by widespread drug resistance. However, the underlying mechanisms have not been revealed. Understanding the targets and resistance mechanisms to anticoccidials is critical to combat this major parasitic disease. In the present study, maduramycin-resistant (MRR) and drug-sensitive (DS) sporozoites of Eimeria tenella were purified for transcriptomic and metabolomic analysis. The transcriptome analysis revealed 5016 differentially expressed genes (DEGs) in MRR compared to DS, and KEGG pathway enrichment analysis indicated that DEGs were involved in spliceosome, carbon metabolism, glycolysis, and biosynthesis of amino acids. In the untargeted metabolomics assay, 297 differentially expressed metabolites (DEMs) were identified in MRR compared to DS, and KEGG pathway enrichment analysis indicated that these DEMs were involved in 10 pathways, including fructose and mannose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, and glutathione metabolism. Targeted metabolomic analysis revealed 14 DEMs in MRR compared to DS, and KEGG pathway analysis indicated that these DEMs were involved in 20 pathways, including fructose and mannose metabolism, glycolysis/gluconeogenesis, and carbon metabolism. Compared to DS, energy homeostasis and amino acid metabolism were differentially regulated in MRR. Our results provide gene and metabolite expression landscapes of E. tenella following maduramycin induction. This study is the first work involving integrated transcriptomic and metabolomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying drug resistance to polyether ionophores in coccidia.PMID:38382267 | DOI:10.1016/j.ijpddr.2024.100526

Unveiling the aromatic differences of low-salt Chinese horse bean-chili-paste using metabolomics and sensomics approaches

Wed, 21/02/2024 - 12:00
Food Chem. 2024 Feb 16;445:138746. doi: 10.1016/j.foodchem.2024.138746. Online ahead of print.ABSTRACTTo achieve salt reduction while ensuring flavor quality of Chinese horse bean-chili-paste (CHCP), we comprehensively explored the effect of indigenous strains Tetragenococcus halophilus and Candida versatilis on the aroma profiles of low-salt CHCP by metabolomics and sensomics analysis. A total of 129 volatiles and 34 aroma compounds were identified by GC × GC-MS and GC-O-MS, among which 29 and 20 volatiles were identified as significant difference compounds and aroma-active compounds, respectively. Inoculation with the two indigenous strains could effectively relieve the undesired acidic and irritative flavor brought by acetic acid and some aldehydes in salt-reduction samples. Meanwhile, inoculated fermentation provided more complex and richer volatiles in low-salt batches, especially for the accumulation of 3-methylbutanol, 1-octen-3-ol, benzeneacetaldehyde, phenylethyl alcohol, and 4-ethyl-phenol etc., which were confirmed as essential aroma compounds of CHCP by recombination and omission tests. The research elucidated the feasibility of bioturbation strategy to achieve salt-reducing fermentation of fermented foods.PMID:38382252 | DOI:10.1016/j.foodchem.2024.138746

Penthorum chinense Pursh leaf tea debittering mechanisms via green tea manufacturing process and its influence on NAFLD-alleviation activities

Wed, 21/02/2024 - 12:00
Food Chem. 2024 Feb 10;445:138715. doi: 10.1016/j.foodchem.2024.138715. Online ahead of print.ABSTRACTThe green-tea manufacturing process showed good effect of flavor improving, debittering and shaping in making Penthorum chinensePursh leaf (PL) tea (PLT), which serves as a polyphenol dietary supplement and beverage raw material. GC-MS results showed that its unpleasant grassy odor decreased by 42.8% due to dodecanal, geranylacetone, and (E)-2-nonenal reduction, coupled with 1-hexadecanol increasing. UPLC-ESI-TOF-MS identified 95 compounds and showed that the debittering effect of green-tea manufacturing process was attributed to decreasing of flavonols and lignans, especially quercetins, kaempferols and luteolins, and increasing of dihydrochalcones which act as sweeteners bitterness-masking agents, while astringency was weakened by reducing delphinidin-3,5-O-diglucoside chloride, kaempferol-7-O-β-d-glucopyranoside, and tannins. The increase of pinocembrins and catechins in aqueous extracts of PLT, maintained its hepatoprotective, NAFLD-alleviation, and hepatofibrosis-prevention activities similar to PL in high fat-diet C57BL/6 mice, with flavonoids, tannins, tannic acids, and some newfound chemicals, including norbergenin, gomisin K2, pseudolaric acid B, tanshinol B, as functional ingredients.PMID:38382251 | DOI:10.1016/j.foodchem.2024.138715

Combined multi-omics approach to analyze the flavor characteristics and formation mechanism of gabaron green tea

Wed, 21/02/2024 - 12:00
Food Chem. 2024 Feb 20;445:138620. doi: 10.1016/j.foodchem.2024.138620. Online ahead of print.ABSTRACTGabaron green tea (GAGT) has unique flavor and health benefits through the special anaerobic treatment. However, how this composite processing affects the aroma formation of GAGT and the regulatory mechanism was rarely reported. This study used nontargeted metabolomics and molecular sensory science to overlay screen differential metabolites and key aroma contributors. The potential regulatory mechanism of anaerobic treatment on the aroma formation of GAGT was investigated by transcriptomics and correlation analyses. Five volatiles: benzeneacetaldehyde, nonanal, geraniol, linalool, and linalool oxide III, were screened as target metabolites. Through the transcriptional-level differential genes screening and analysis, some CsERF transcription factors in the ethylene signaling pathway were proposed might participate the response to the anaerobic treatment. They might regulate the expression of related genes in the metabolic pathway of the target metabolites thus affecting the GAGT flavor. The findings of this study provide novel information on the flavor and its formation of GAGT.PMID:38382249 | DOI:10.1016/j.foodchem.2024.138620

Identification of trans-genus biomarkers for early diagnosis of intestinal schistosomiasis and progression of gut pathology in a mouse model using metabolomics

Wed, 21/02/2024 - 12:00
PLoS Negl Trop Dis. 2024 Feb 21;18(2):e0011966. doi: 10.1371/journal.pntd.0011966. eCollection 2024 Feb.ABSTRACTSchistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal granulomatous inflammation and bleeding. The current diagnostic method is inaccurate and delayed, hence, biomarker identification using metabolomics has been applied. However, previous studies only investigated infection caused by one Schistosoma spp., leaving a gap in the use of biomarkers for other species. No study focused on understanding the progression of intestinal disease. Therefore, we aimed to identify early gut biomarkers of infection with three Schistosoma spp. and progression of intestinal pathology. We infected 3 groups of mice, 3 mice each, with Schistosoma mansoni, Schistosoma japonicum or Schistosoma mekongi and collected their feces before and 1, 2, 4 and 8 weeks after infection. Metabolites in feces were extracted and identified using mass spectrometer-based metabolomics. Metabolites were annotated and analyzed with XCMS bioinformatics tool and Metaboanalyst platform. From >36,000 features in all conditions, multivariate analysis found a distinct pattern at each time point for all species. Pathway analysis reported alteration of several lipid metabolism pathways as infection progressed. Disturbance of the glycosaminoglycan degradation pathway was found with the presence of parasite eggs, indicating involvement of this pathway in disease progression. Biomarkers were discovered using a combination of variable importance for projection score cut-off and receiver operating characteristic curve analysis. Five molecules met our criteria and were present in all three species: 25-hydroxyvitamin D2, 1α-hydroxy-2β-(3-hydroxypropoxy) vitamin D3, Ganoderic acid Md, unidentified feature with m/z 455.3483, and unidentified feature with m/z 456.3516. These molecules were proposed as trans-genus biomarkers of early schistosomiasis. Our findings provide evidence for disease progression in intestinal schistosomiasis and potential biomarkers, which could be beneficial for early detection of this disease.PMID:38381759 | DOI:10.1371/journal.pntd.0011966

MSC-derived small extracellular vesicles exert cardioprotective effect through reducing VLCFAs and apoptosis in human cardiac organoid IRI model

Wed, 21/02/2024 - 12:00
Stem Cells. 2024 Feb 21:sxae015. doi: 10.1093/stmcls/sxae015. Online ahead of print.ABSTRACTCardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for 31% of all deaths globally. Myocardial ischemia-reperfusion injury (IRI), a common complication of CVDs, is a major cause of mortality and morbidity. Studies have shown efficacious use of mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) to mitigate IRI in animals, but few research has been done on human-related models. In this study, human embryonic stem cell-derived chambered cardiac organoid (CCOs) was used as a model system to study the effects of MSC-derived small extracellular vesicles (sEVs) on myocardial IRI. The results revealed that MSC-sEVs treatment reduced apoptosis and improved contraction resumption of the CCOs. Metabolomics analysis showed that this effect could be attributed to sEVs' ability to prevent the accumulation of unsaturated very long chain fatty acids (VLCFAs). This was corroborated when inhibition of fatty acid synthase (FASN), which was reported to reduce VLCFAs, produced a similar protective effect to sEVs. Overall, this study uncovered the mechanistic role of sEVs in mitigating IRI that involves preventing the accumulation of unsaturated VLCFA, decreasing cell death, and improving contraction resumption in CCOs.PMID:38381602 | DOI:10.1093/stmcls/sxae015

Electroacupuncture at ST36 modulates the intestinal microecology and may help repair the intestinal barrier in the rat model of severe acute pancreatitis

Wed, 21/02/2024 - 12:00
Microb Biotechnol. 2024 Feb;17(2):e14401. doi: 10.1111/1751-7915.14401.ABSTRACTSevere acute pancreatitis (SAP) onset and development are closely associated with intestinal barrier injury. Evidence from clinical practice and research has shown that electroacupuncture (EA) at the Zusanli (ST36) acupoint can improve intestinal barrier function and abdominal symptoms in patients with SAP; however, the specific mechanisms of action remain unclear. This study aimed to observe the changes in the intestinal microbiota and metabolites in SAP rats and to explore the effect of EA at ST36 on intestinal barrier injury in SAP rats. 16S rRNA gene sequencing combined with microbial diversity analysis, short-chain fatty acids (SCFAs)-targeted metabolomics, immunohistochemistry, immunofluorescence, western blotting, and other techniques were used to explore the mechanism of EA at bilateral ST36 acupoints on SAP-related intestinal barrier injury. Our results showed that EA at ST36 could repair intestinal barrier injury by modulating intestinal microecology, thereby reducing intestinal inflammation, restoring intestinal function, and ultimately alleviating the prognosis of SAP. Our study provides new insights into the mechanisms and treatment of intestinal barrier injury in patients with SAP from the perspectives of microbiota and SCFAs regulation.PMID:38381095 | DOI:10.1111/1751-7915.14401

Non-targeted metabolomic analysis reveals the mechanism of quality formation of citrus flower-green tea

Wed, 21/02/2024 - 12:00
J Sci Food Agric. 2024 Feb 21. doi: 10.1002/jsfa.13405. Online ahead of print.ABSTRACTBACKGROUND: Citrus flower-green tea (CT) is a scented tea processed from green tea (GT) and fresh citrus flower, which is favored by consumers due to its potential health benefits and unique citrus flavor. This study evaluated the quality of CT and revealed the mechanism of its quality formation.RESULTS: The CT had a significant citrus flavor and a good antioxidant activity, and its sensory quality was superior to that of GT. Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) analysis revealed that the scenting process resulted in a significant increase of alkenes such as β-pinene, trans-β-ocimene, α-farnesene, isoterpinolene, and γ-terpinene, as well as a significant decrease of alcohols such as α-terpineol, L-menthol, and linalool in CT in comparision with GT. Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis revealed that the levels of flavonoids (such as neohesperidin, hesperidin, tangeritin, hesperetin 5-O-glucoside, and nobiletin) and alkaloids (such as trigonelline and theobromine) in CT increased significantly after scenting process, while the levels of amino acids (such as valine and L-phenylalanine) and organic acids (such as ascorbic acid) decreased significantly.CONCLUSION: These observations showed that the scenting process promoted the absorption of aroma from citrus flowers by GT and the changes in its non-volatile metabolites, leading to the formation of citrus flavor quality in CT. This article is protected by copyright. All rights reserved.PMID:38380915 | DOI:10.1002/jsfa.13405

Sustainability implications and relevance of using omics sciences to investigate cheeses with protected designation of origin (PDO)

Wed, 21/02/2024 - 12:00
J Sci Food Agric. 2024 Feb 21. doi: 10.1002/jsfa.13403. Online ahead of print.ABSTRACTCheese, a fundamental component of the human diet and a cornerstone of the global food economy, holds significance beyond its role as a market commodity, playing a crucial part in the cultural identity of various social communities. The intricate natural aging process, known as maturation, involves a series of reactions that induce changes in physical, biochemical, microbiological, and particularly sensory characteristics, making it a complex aspect of cheese production. Recently, the adoption of omics sciences (e.g., metagenomics, metabolomics, proteomics) in PDO cheese studies has emerged as a new trend. This mini-summary aims to outline the relationship between omics studies in these food matrices and all the sustainability facets of the production chain in general, as well as discuss and recognize that the importance of these studies goes beyond comprehending the cheesebiome; it extends to fostering and ensuring the sustainability of the production chain. In this context, numerous studies in recent years have linked the identification of intrinsic characteristics of PDO cheeses through omics sciences to crucial sustainability themes such as territoriality, biodiversity, and the preservation of product authenticity. The trajectory suggests that increasingly multidisciplinary studies, spanning various omics sciences, will not only contribute to characterizing these products but also address sustainability aspects directly related to the production chain (e.g., authenticity, microbial biodiversity, functionality). This expansion underscores the multidisciplinary nature of these studies, broadening their social impact beyond the academic realm. Consequently, these pivotal studies play a crucial role in advancing discussions on PDO products and sustainability. This article is protected by copyright. All rights reserved.PMID:38380878 | DOI:10.1002/jsfa.13403

A study integrated metabolomics and network pharmacology to investigate the effects of Shicao in alleviating acute liver injury

Wed, 21/02/2024 - 12:00
J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117369. doi: 10.1016/j.jep.2023.117369. Epub 2023 Oct 28.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases.AIM OF STUDY: To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury.METHODS: A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network.RESULTS: Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao.CONCLUSION: This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.PMID:38380571 | DOI:10.1016/j.jep.2023.117369

Metabolomic age and risk of 50 chronic diseases in community-dwelling adults: A prospective cohort study

Wed, 21/02/2024 - 12:00
Aging Cell. 2024 Feb 21:e14125. doi: 10.1111/acel.14125. Online ahead of print.ABSTRACTIt is unclear how metabolomic age is associated with the risk of a wide range of chronic diseases. Our analysis included 110,692 participants (training: n = 27,673; testing: n = 27,673; validating: n = 55,346) aged 39-71 years at baseline (2006-2010) from the UK Biobank. Incident chronic diseases were identified using inpatient records, or death registers until January 2021. Predicted metabolomic age was trained and tested based on 168 metabolomics. Metabolomic age was linked to the risk of 50 diseases in the validation dataset. The median follow-up duration for individual diseases ranged from 11.2 years to 11.9 years. After controlling for false discovery rate, chronological age-adjusted age gap (CAAG) was significantly associated with the incidence of 25 out of 50 chronic diseases. After adjustment for full covariates, associations with 15 chronic diseases remained significant. Greater CAAG was associated with increased risk of eight cardiometabolic disorders (including cardiovascular diseases and diabetes), some cancers, alcohol use disorder, chronic obstructive pulmonary disease, chronic kidney disease, chronic liver disease and age-related macular degeneration. The association between CAAG and risk of peripheral vascular disease, other cardiac diseases, fracture, cataract and thyroid disorder was stronger among individuals with unhealthy diet than in those with healthy diet. The association between CAAG and risk of some conditions was stronger in younger individuals, those with metabolic disorders or low education. Metabolomic age plays an important role in the development of multiple chronic diseases. Healthy diet and high education may mitigate the risk for some chronic diseases due to metabolomic age acceleration.PMID:38380547 | DOI:10.1111/acel.14125

Transcriptomic and metabolic analysis unveils the mechanism behind leaf color development in <em>Disanthus cercidifolius</em> var. <em>longipes</em>

Wed, 21/02/2024 - 12:00
Front Mol Biosci. 2024 Feb 6;11:1343123. doi: 10.3389/fmolb.2024.1343123. eCollection 2024.ABSTRACTIntroduction: Leaf coloration in Disanthus cercidifolius var. longipes results from the interplay of various pigments undergoing complex catalytic reactions. Methods: We aimed to elucidate the mechanisms of pigment biosynthesis affecting leaf color transition in D. cercidifolius var. longipes by analyzing variations in pigment accumulation and levels of gene expression. Results: We identified 468, 577, and 215 differential metabolites in green leaves (GL), gradual-color-changing leaves (GCCL), and red leaves (RL), respectively, with 94 metabolites shared across all comparisons. Metabolite accumulation patterns were similar among GL, GCCL, and RL, with flavonoids being the main differential metabolites. Delphinidin, malvidin, and petunidin derivatives were mostly accumulated in GCCL, whereas cyanidin, pelargonidin, and peonidin derivatives accumulated in RL. Transcriptome sequencing was used to identify differentially expressed genes. The expression of anthocyanin biosynthetic pathway genes was associated with anthocyanin accumulation patterns. Discussion: Our findings reveal that the content of delphinidin, malvidin, petunidin, and carotenoids collectively determines the gradual transition of leaf color from green in spring and summer to green, purple, and orange-yellow in early autumn, whereas the content of cyanidin, peonidin, pelargonidin, and carotenoids together causes the autumnal transition to red or orange-red colors as leaves of D. cercidifolius var. longipes age.PMID:38380429 | PMC:PMC10876866 | DOI:10.3389/fmolb.2024.1343123

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