PubMed

Front Microbiol. 2023 Jun 14;14:1188455. doi: 10.3389/fmicb.2023.1188455. eCollection 2023.ABSTRACTPharmacological treatment of inflammatory bowel disease (IBD) is inefficient and difficult to discontinue appropriately, and enterobacterial interactions are expected to provide a new target for the treatment of IBD. We collected recent studies on the enterobacterial interactions among the host, enterobacteria, and their metabolite products and discuss potential therapeutic options. Intestinal flora interactions in IBD are affected in the reduced bacterial diversity, impact the immune system and are influenced by multiple factors such as host genetics and diet. Enterobacterial metabolites such as SCFAs, bile acids, and tryptophan also play important roles in enterobacterial interactions, especially in the progression of IBD. Therapeutically, a wide range of sources of probiotics and prebiotics exhibit potential therapeutic benefit in IBD through enterobacterial interactions, and some have gained wide recognition as adjuvant drugs. Different dietary patterns and foods, especially functional foods, are novel therapeutic modalities that distinguish pro-and prebiotics from traditional medications. Combined studies with food science may significantly improve the therapeutic experience of patients with IBD. In this review, we provide a brief overview of the role of enterobacteria and their metabolites in enterobacterial interactions, discuss the advantages and disadvantages of the potential therapeutic options derived from such metabolites, and postulate directions for further research.PMID:37389342 | PMC:PMC10303177 | DOI:10.3389/fmicb.2023.1188455

Front Plant Sci. 2023 Jun 14;14:1175012. doi: 10.3389/fpls.2023.1175012. eCollection 2023.ABSTRACTINTRODUCTION: Titanium dioxide nanoparticles (TiO2 NPs) are among the most widely used inorganic nanomaterials in industry, medicine and food additives. There are increasing concerns regarding their potential risks to plants and the environment. Mulberry trees are widely grown in China due to their high survival rate and ability to aid ecological recovery.METHODS: Herein, the effects of TiO2 NPs with different concentrations (100, 200, 400 and 800 mg/L) on the growth and physiology of the mulberry tree were systematically evaluated in aspects of physiology, transcriptomics and metabolomics.RESULTS: Results showed that TiO2 NPs could be absorbed by the mulberry sapling root system and be transferred to the plant shoot. This results in the destruction of mulberry sapling root and leaf tissue. Furthermore, the number of chloroplasts and their pigment contents were reduced and the homeostasis of metal ions was disrupted. The toxic effects of TiO2 NPs attenuated the mulberry sapling's stress resistance, the contents of malondialdehyde in 100 mg/L, 200 mg/L 400 mg/L and 800 mg/L treatment groups increased by 87.70%, 91.36%, 96.57% and 192.19% respectively compared with the control group. The transcriptomic data showed that TiO2 NPs treatment mainly affected the expression of genes related to energy synthesis and transport, protein metabolism, and response to stress. Meanwhile, the results of metabolomics showed that 42 metabolites produced significant differences in mulberry, of which 26 differential metabolites were up-regulated in expression and 16 differential metabolites were down-regulated, mainly including metabolic pathways such as secondary metabolite biosynthesis, citric acid cycle, and tricarboxylic acid cycle, and was not conducive to the seed germination and or growth of the mulberry sapling.DISCUSSION: This study enriches the understanding of the effects of TiO2 NPs on plants and provides a reference for the comprehensive scientific assessment of the potential risks of nanomaterials on plants.PMID:37389295 | PMC:PMC10301732 | DOI:10.3389/fpls.2023.1175012

Front Plant Sci. 2023 Jun 14;14:1187551. doi: 10.3389/fpls.2023.1187551. eCollection 2023.ABSTRACTINTRODUCTION: Apricot fruits are edible and serve as a source of medicinal compounds. Flavonols are important plant secondary metabolites that have antioxidant and antitumor effects and may promote cardiovascular health.METHODS: The flavonoid content in three stages of the 'Kuijin' and the 'Katy' was observed, followed by the combination of metabolome and transcriptome analysis to explore the metabolic basis of flavonol synthesis.RESULTS: The differences in the metabolite contents between stages (of the same cultivar) and between cultivars (at the same stage) revealed decreases in the flavonoid content as fruits developed (i.e., from 0.28 mg/g to 0.12 mg/g in 'Kuijin' and from 0.23 mg/g to 0.05 mg/g in 'Katy'). To decipher the regulation of flavonol synthesis in apricot (Prunus armeniaca L.), the metabolomes and transcriptomes of fruit pulp at three developmental stages of 'Kuijin' and the 'Katy' were analyzed. A total of 572 metabolites were detected in 'Kuijin' and the 'Katy' pulp, including 111 flavonoids. The higher flavonol content young 'Kuijin' fruits at 42 days after full bloom is mainly due to 10 types of flavonols. Three pairs of significant differences in flavonol content were identified. From these three comparison groups, three structural genes were strongly correlated with the levels of 10 types of flavonols (Pearson correlation coefficients > 0.8, p value < 0.05), including PARG09190, PARG15135, and PARG17939. The weighted gene co-expression network analysis showed that the turquoise module genes were highly correlated with flavonol contents (P < 0.01). There were 4897 genes in this module. Out of 4897 genes, 28 transcription factors are associated with 3 structural genes based on weight value. Two of the transcription factors are not only associated with PARG09190 but also with PARG15135, indicating their critical importance in the flavonols biosynthesis. The two TFs are PARG27864 and PARG10875.DISCUSSION: These findings provide new insights into the biosynthesis of flavonols and may explain the significant differences in flavonoid content between the 'Kuijin' and the 'Katy' cultivars. Moreover, it will aid in genetic improvement to enhance the nutritional and health value of apricots.PMID:37389287 | PMC:PMC10303810 | DOI:10.3389/fpls.2023.1187551

World J Gastroenterol. 2023 Jun 14;29(22):3534-3547. doi: 10.3748/wjg.v29.i22.3534.ABSTRACTBACKGROUND: Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC).AIM: To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS: According to the inclusion and exclusion criteria, 27 patients with ALC and 24 healthy controls (HCs) were selected, and plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces. Also, the correlation between metabolites and clinical features was analyzed.RESULTS: More than 300 common metabolites were identified in the plasma and feces of patients with ALC. Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways. Compared to HCs, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. Moreover, we established a P/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score.CONCLUSION: The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC. These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.PMID:37389241 | PMC:PMC10303510 | DOI:10.3748/wjg.v29.i22.3534

iScience. 2023 Jun 7;26(7):107046. doi: 10.1016/j.isci.2023.107046. eCollection 2023 Jul 21.ABSTRACTWeight loss interventions, including dietary changes, pharmacotherapy, or bariatric surgery, prevent many of the adverse consequences of obesity, and may also confer intervention-specific benefits beyond those seen with decreased weight alone. We compared the molecular effects of different interventions on liver metabolism to understand the mechanisms underlying these benefits. Male rats on a high-fat, high-sucrose diet underwent sleeve gastrectomy (SG) or intermittent fasting with caloric restriction (IF-CR), achieving equivalent weight loss. The interventions were compared to ad-libitum (AL)-fed controls. Analysis of liver and blood metabolome and transcriptome revealed distinct and sometimes contrasting metabolic effects between the two interventions. SG primarily influenced one-carbon metabolic pathways, whereas IF-CR increased de novo lipogenesis and glycogen storage. These findings suggest that the unique metabolic pathways affected by SG and IF-CR contribute to their distinct clinical benefits, with bariatric surgery potentially influencing long-lasting changes through its effect on one-carbon metabolism.PMID:37389181 | PMC:PMC10300224 | DOI:10.1016/j.isci.2023.107046

Oncoimmunology. 2023 Jun 27;12(1):2227510. doi: 10.1080/2162402X.2023.2227510. eCollection 2023.ABSTRACTToll-like receptor 3 (TLR3) agonists such as polyinosinic:polycytidylic acid (poly(I:C)) have immunostimulatory effects that can be taken advantage of to induce anticancer immune responses in preclinical models. In addition, poly(I:C) has been introduced into clinical trials to demonstrate its efficacy as an adjuvant and to enhance the immunogenicity of locally injected tumors, thus reverting resistance to PD-L1 blockade in melanoma patients. Here, we report the pharmacokinetic, pharmacodynamic, mechanistic and toxicological profile of a novel TLR3 agonist, TL-532, a chemically synthesized double-stranded RNA that is composed by blocks of poly(I:C) and poly(A:U) (polyadenylic - polyuridylic acid). In preclinical models, we show that TL-532 is bioavailable after parenteral injection, has an acceptable toxicological profile, and stimulates the production of multiple chemokines and interleukins that constitute pharmacodynamic markers of its immunostimulatory action. When given at a high dose, TL-532 monotherapy reduced the growth of bladder cancers growing on mice. In addition, in immunodeficient mice lacking formylpeptide receptor-1 (FPR1), TL-532 was able to restore the response of orthotopic subcutaneous fibrosarcoma to immunogenic chemotherapy. Altogether, these findings may encourage further development of TL-532 as an immunotherapeutic anticancer agent.PMID:37389102 | PMC:PMC10305499 | DOI:10.1080/2162402X.2023.2227510

Trends Analyt Chem. 2023 Aug;165:117117. doi: 10.1016/j.trac.2023.117117. Epub 2023 Jun 1.ABSTRACTTissues and other cell populations are highly heterogeneous at the cellular level, owing to differences in expression and modifications of proteins, polynucleotides, metabolites, and lipids. The ability to assess this heterogeneity is crucial in understanding numerous biological phenomena, including various pathologies. Traditional analyses apply bulk-cell sampling, which masks the potentially subtle differences between cells that can be important in understanding of biological processes. These limitations due to cell heterogeneity inspired significant efforts and interest toward the analysis of smaller sample sizes, down to the level of individual cells. Among the emerging techniques, the unique capabilities of capillary electrophoresis coupled with mass spectrometry (CE-MS) made it a prominent technique for proteomics and metabolomics analysis at the single-cell level. In this review, we focus on the application of CE-MS in the proteomic and metabolomic profiling of single cells and highlight the recent advances in sample preparation, separation, MS acquisition, and data analysis.PMID:37388554 | PMC:PMC10306258 | DOI:10.1016/j.trac.2023.117117

Front Pharmacol. 2023 Jun 14;14:1235626. doi: 10.3389/fphar.2023.1235626. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fphar.2022.961087.].PMID:37388450 | PMC:PMC10303910 | DOI:10.3389/fphar.2023.1235626

Cardiovasc Ther. 2023 Jun 21;2023:8774971. doi: 10.1155/2023/8774971. eCollection 2023.ABSTRACTBACKGROUND: To date, immunotherapy for patients with malignant tumors has shown a significant association with myocarditis. However, the mechanism of metabolic reprogramming changes for immunotherapy-related cardiotoxicity is still not well understood.METHODS: The CD45+ single-cell RNA sequencing (scRNA-seq) of the Pdcd1-/-Ctla4+/- and wild-type mouse heart in GSE213486 was downloaded to demonstrate the heterogeneity of immunocyte atlas in immunotherapy-related myocarditis. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) spectrum metabolomics analysis detects the metabolic network differences. The drug prediction, organelle level interaction, mitochondrial level regulatory network, and phosphorylation site prediction for key regulators have also been screened via multibioinformatics analysis methods.RESULTS: The scRNA analysis shows that the T cell is the main regulatory cell subpopulation in the pathological progress of immunotherapy-related myocarditis. Mitochondrial regulation pathway significantly participated in pseudotime trajectory- (PTT-) related differential expressed genes (DEGs) in the T cell subpopulation. Additionally, both the gene set enrichment analysis (GSEA) of PTT-related DEGs and LC-MS/MS metabolomics analysis showed that mitochondrial-regulated glycerolipid metabolism plays a central role in metabolic reprogramming changes for immunotherapy-related cardiotoxicity. Finally, the hub-regulated protease of diacylglycerol kinase zeta (Dgkz) was significantly identified and widely played various roles in glycerolipid metabolism, oxidative phosphorylation, and lipid kinase activation.CONCLUSION: Mitochondrial-regulated glycerolipid metabolism, especially the DGKZ protein, plays a key role in the metabolic reprogramming of immunotherapy-related myocarditis.PMID:37388276 | PMC:PMC10307211 | DOI:10.1155/2023/8774971

Plant Biotechnol J. 2023 Jun 30. doi: 10.1111/pbi.14112. Online ahead of print.ABSTRACTLow temperature is the main environmental factor affecting the yield, quality and geographical distribution of crops, which significantly restricts development of the fruit industry. The NAC (NAM, ATAF1/2 and CUC2) transcription factor (TF) family is involved in regulating plant cold tolerance, but the mechanisms underlying these regulatory processes remain unclear. Here, the NAC TF MdNAC104 played a positive role in modulating apple cold tolerance. Under cold stress, MdNAC104-overexpressing transgenic plants exhibited less ion leakage and lower ROS (reactive oxygen species) accumulation, but higher contents of osmoregulatory substances and activities of antioxidant enzymes. Transcriptional regulation analysis showed that MdNAC104 directly bound to the MdCBF1 and MdCBF3 promoters to promote expression. In addition, based on combined transcriptomic and metabolomic analyses, as well as promoter binding and transcriptional regulation analyses, we found that MdNAC104 stimulated the accumulation of anthocyanin under cold conditions by upregulating the expression of anthocyanin synthesis-related genes, including MdCHS-b, MdCHI-a, MdF3H-a and MdANS-b, and increased the activities of the antioxidant enzymes by promoting the expression of the antioxidant enzyme-encoding genes MdFSD2 and MdPRXR1.1. In conclusion, this study revealed the MdNAC104 regulatory mechanism of cold tolerance in apple via CBF-dependent and CBF-independent pathways.PMID:37387580 | DOI:10.1111/pbi.14112

Expert Rev Anti Infect Ther. 2023 Jun 30. doi: 10.1080/14787210.2023.2232112. Online ahead of print.ABSTRACTOBJECTIVES: Evaluation of the antifungal properties of Tamarix nilotica fractions against Candida albicans clinical isolates.METHODS: The in vitro antifungal potential was evaluated by agar well diffusion and broth microdilution methods. The antibiofilm potential was assessed by crystal violet, scanning electron microscopy (SEM), and qRT-PCR. The in vivo antifungal activity was evaluated by determining the burden in the lung tissues of infected mice, histopathological, immunohistochemical studies, and ELISA.RESULTS: Both the dichloromethane (DCM) and ethyl acetate (EtOAc) fractions had minimum inhibitory concentration (MIC) values of 64-256 and 128-1024 μg/mL, respectively. SEM examination showed that the DCM fraction decreased the biofilm formation capacity of the treated isolates. A significant decline in biofilm gene expression was observed in 33.33% of the DCM-treated isolates. A considerable decline in the CFU/g lung count in infected mice was observed, and histopathological examinations revealed that the DCM fraction maintained the lung tissue architecture. Immunohistochemical investigations indicated that the DCM fraction significantly (p < 0.05) decreased the expression of pro-inflammatory and inflammatory cytokines (TNF-α, NF-kB, COX-2, IL-6, and IL-1β) in the immunostained lung sections. The phytochemical profiling of DCM and EtOAc fractions was performed using Liquid chromatography-mass spectrometry (LC-ESI-MS/MS).CONCLUSION: T. nilotica DCM fraction could be a significant source of natural products with antifungal activity against C. albicans infections.PMID:37387417 | DOI:10.1080/14787210.2023.2232112

J Dent Res. 2023 Jun 30:220345231176522. doi: 10.1177/00220345231176522. Online ahead of print.ABSTRACTBone defect (BD) caused by trauma, infection, congenital defects, or neoplasia is a major cause of physical limitation. Distraction osteogenesis (DO) is a highly effective procedure for bone regeneration, while the concrete mechanism remains unknown. In this study, canine DO and BD models of the mandible were established. The results of micro-computed tomography and histological staining revealed that DO led to an increased mineralized volume fraction and robust new bone formation; in contrast, BD demonstrated incomplete bone union. Mesenchymal stem cells (MSCs) from DO and BD calluses were isolated and identified. Compared with BD-MSCs, DO-MSCs were found to have a stronger osteogenic capability. Single-cell RNA sequencing analysis was further performed to comprehensively define cell differences between mandibular DO and BD calluses. Twenty-six clusters of cells representing 6 major cell populations were identified, including paired related homeobox 1-expressing MSCs (PRRX1+MSCs), endothelial cells (ECs), T cells, B cells, neutrophils, and macrophages. Interestingly, 2 subpopulations in PRRX1+MSCs in the DO group were found to express the marker of neural crest cells (NCCs) and were associated with the process of epithelial-mesenchymal transition. The immunofluorescence assay was performed to further corroborate these results in vivo and in vitro, experimentally validating that continuous distraction maintained the PRRX1+MSCs in an embryonic-like state. Finally, we used CRISPR/Cas9 to knock out (KO) PRRX1 in the context of DO, which significantly blunted the capability of jawbone regeneration, resulting in a diminished NCC-like program and reduction of new bone volume. In addition, the ability of osteogenesis, cell migration, and proliferation in cultured PRRX1KO MSCs was inhibited. Taken together, this study provides a novel, comprehensive atlas of the cell fates in the context of DO regeneration, and PRRX1+MSCs act essential roles.PMID:37387366 | DOI:10.1177/00220345231176522

Stud Health Technol Inform. 2023 Jun 29;305:432-435. doi: 10.3233/SHTI230524.ABSTRACTThe aim of metabolomics research is to identify the metabolites that play a role in various biological traits and diseases. This scoping review provides an overview of the current state of metabolomics studies that focus on the Qatari population. Our findings indicate that few studies have been conducted on this population, with a focus on diabetes, dyslipidemia, and cardiovascular disease. Blood samples were the primary source of metabolite identification, and several potential biomarkers for these diseases were proposed. To the best of our knowledge, this is the first scoping review that presents an overview of metabolomics studies in Qatar.PMID:37387058 | DOI:10.3233/SHTI230524

J Agric Food Chem. 2023 Jun 29. doi: 10.1021/acs.jafc.3c02562. Online ahead of print.ABSTRACTThe interaction of pectin and gut microbiota plays an important role in maintaining animal and human health, but this interaction is not fully understood. Here, the impact of pectin supplementation on substrate dynamics and gut microbiota (in the terminal ileum and feces) was integrally investigated in a fistula pig model. Our results showed that a pectin-supplemented diet (PEC) decreased the concentrations of starch, cellulose, and butyrate in feces but not in the terminal ileum. Metagenomic sequencing revealed that PEC had a low impact on the ileal microbiota but significantly increased plant polysaccharide-degrading genera (e.g., Bacteroides, Alistipes, and Treponema) in feces. Additionally, CAZyme profiling indicated that PEC reduced GH68 and GH8 for oligosaccharide degradation in the ileal microbiome, while it enriched GH5, GH57, and GH106 for degradation of carbohydrate substrates in feces. Metabolomic analysis confirmed that PEC increased metabolites involved in carbohydrate metabolism including glucuronate and aconitate. Collectively, pectin could promote complex carbohydrate substrate degradation in the hindgut via modulating the gut microbiota.PMID:37386754 | DOI:10.1021/acs.jafc.3c02562

Eur Respir J. 2023 Jun 29:2201374. doi: 10.1183/13993003.01374-2022. Online ahead of print.ABSTRACTBACKGROUND: Virus infections drive COPD exacerbations and progression. Anti-viral immunity centers on the activation of virus-specific CD8+ T cells by viral epitopes presented on MHC class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialized intracellular protein degradation machine, which is induced by anti-viral cytokines in infected cells.METHODS: We here analysed the effects of CS on cytokine and virus-mediated induction of the immunoproteasome in vitro, ex vivo and in vivo using RNA and Western blot analyses. CD8+ T cell activation was determined in co-culture assays with CS-exposed Influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of CS on inflammatory antigen presentation in lung cells. IAV-specific CD8+ T cell numbers were determined in peripheral patients' blood using tetramer-technology.RESULTS: CS impaired the induction of the immunoproteasome by cytokine signaling and viral infection in lung cells in vitro, ex vivo and in vivo. CS also altered the peptide repertoire of antigens presented on MHC class I under inflammatory conditions. Importantly, MHC class I-mediated activation of IAV-specific CD8+ T cells was dampened by CS. COPD patients exhibited reduced numbers of circulating IAV-specific CD8+ T cells compared to healthy controls and asthmatics.CONCLUSION: Our data indicate that cigarette smoke interferes with MHC class I antigen generation and presentation and thereby contributes to impaired activation of CD8+ T cells upon virus infection. This adds important mechanistic insight on how cigarette smoke mediates increased susceptibility of smokers and COPD patients to viral infections.PMID:37385655 | DOI:10.1183/13993003.01374-2022

Int J Antimicrob Agents. 2023 Jun 27:106907. doi: 10.1016/j.ijantimicag.2023.106907. Online ahead of print.ABSTRACTSalmonella enterica (SE) is a food-borne pathogen that poses a severe threat to both poultry production and human health. Antibiotics are critical for the initial treatment of bacterial infections. However, the overuse and misuse of antibiotics can result in the rapid evolution of antibiotic-resistant bacteria, while the discovery and development of new antibiotics are declining. Therefore, understanding antibiotic resistance mechanisms and developing novel control measures are highly valued. In the present study, GC-MS-based metabolomics analysis was performed to determine the metabolic profile of the gentamicin sensitive (SE-S) and resistant Salmonella enterica (SE-R). Fructose was identified as a crucial biomarker. Further analysis demonstrated a global depressed central carbon metabolism and energy metabolism in SE-R. The decrease in the pyruvate cycle reduces the production of NADH and ATP, ultimately causing a decrease in membrane potential, which contributes to gentamicin resistance. Exogenous fructose potentiated gentamicin's effectiveness in killing SE-R by promoting the pyruvate cycle, NADH, ATP and membrane potential, thereby increasing gentamicin intake. Additionally, fructose plus gentamicin improved the survival rate of chicken infected with gentamicin-resistant Salmonella in vivo. Given that metabolite structures are conserved across species, fructose identified from bacterial could be used as a biomarker for breeding for disease-resistance phenotypes in chicken. Therefore, we propose a novel strategy for fighting against antibiotic-resistant Salmonella enterica by exploring molecules suppressed by antibiotics and provide a new approach to find targets from the pathogen's perspective for chicken disease resistance breeding.PMID:37385564 | DOI:10.1016/j.ijantimicag.2023.106907

Exp Eye Res. 2023 Jun 27:109562. doi: 10.1016/j.exer.2023.109562. Online ahead of print.ABSTRACTCells communicate with each other using vesicles of varying sizes, including a specific repertoire known as exosomes. We isolated aqueous humor (AH)-derived vesicles using two different methods: ultracentrifugation and an exosome isolation kit. We confirmed a unique vesicle size distribution in the AH derived from control and primary open-angle glaucoma (POAG) patients using various techniques, including Nanotracker, dynamic light scattering, atomic force imaging, and electron microscopy. Bonafide vesicle and/or exosome markers were present by dot blot in both control and POAG AH-derived vesicles. Marker levels differed between POAG and control samples, while non-vesicle negative markers were absent in both. Quantitative labeled (iTRAQ) proteomics showed a reduced presence of a specific protein, STT3B, in POAG compared to controls, which was further confirmed using dot blot, Western blot, and ELISA assays. Along the lines of previous findings with AH profiles, we found vast differences in the total phospholipid composition of AH vesicles in POAG compared to controls. Electron microscopy further showed that the addition of mixed phospholipids alters the average size of vesicles in POAG. We found that the cumulative particle size of type I collagen decreased in the presence of Cathepsin D, which normal AH vesicles were able to protect against, but POAG AH vesicles did not. AH alone had no effect on collagen particles. We observed a protective effect on collagen particles with an increase in artificial vesicle sizes, consistent with the protective effects observed with larger control AH vesicles but not with the smaller-sized POAG AH vesicles. Our experiments suggest that AH vesicles in the control group provide greater protection for collagen beams compared to POAG, and their increased vesicle sizes are likely contributing factors to this protection.PMID:37385533 | DOI:10.1016/j.exer.2023.109562

Chemosphere. 2023 Jun 27:139302. doi: 10.1016/j.chemosphere.2023.139302. Online ahead of print.ABSTRACTSorption regulates the dispersion of pesticides from cropped areas to surrounding water bodies as well as their persistence. Assessing the risk of water contamination and evaluating the efficiency of mitigation measures, requires fine-resolution sorption data and a good knowledge of its drivers. This study aimed to assess the potential of a new approach combining chemometric and soil metabolomics to estimate the adsorption and desorption coefficients of a range of pesticides. It also aims to identify and characterise key components of soil organic matter (SOM) driving the sorption of these pesticides. We constituted a dataset of 43 soils from Tunisia, France and Guadeloupe (West Indies), covering extensive ranges of texture, organic carbon and pH. We performed untargeted soil metabolomics by liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). We measured the adsorption and desorption coefficients of three pesticides namely glyphosate, 2,4-D and difenoconazole for these soils. We developed Partial Least Square Regression (PLSR) models for the prediction of the sorption coefficients from the RT-m/z matrix and conducted further ANOVA analyses to identify, annotate and characterise the most significant constituents of SOM in the PLSR models. The curated metabolomics matrix yielded 1213 metabolic markers. The prediction performance of the PLSR models was generally high for the adsorption coefficients Kdads (0.3 < R2 < 0.8) and for the desorption coefficients Kfdes (0.6 < R2 < 0.8) but low for ndes (0.03 < R2 < 0.3). The most significant features in the predictive models were annotated with a confidence level of 2 or 3. The molecular descriptors of these putative compounds suggest that the pool of SOM compounds driving glyphosate sorption is reduced compared to 2,4-D and difenoconazole, and these compounds are generally more polar. This approach can provide estimates of the adsorption and desorption coefficients of pesticides, including polar pesticide, for contrasted pedoclimates.PMID:37385484 | DOI:10.1016/j.chemosphere.2023.139302

Phytochemistry. 2023 Jun 27:113777. doi: 10.1016/j.phytochem.2023.113777. Online ahead of print.ABSTRACTThe undifferentiated cambial meristematic cell (CMC) has been recognized as a value-added production platform for plant natural products in comparison to the dedifferentiated plant cell line (DDC). In a time-based approach at 0, 24, 48, and 72 h, the present study aimed at investigating the phytochemical metabolome of methyl jasmonate (MeJA)-elicited CMC cultures derived from sweet basil (Ocimum basilicum L.), including primary and secondary metabolites analyzed using GC/TOF-MS post-silylation and RP-UPLC-C18-FT-MS/MS, respectively, as well as the analysis of aroma composition using headspace SPME-GC-MS. The results revealed a stress response in primary metabolism manifested by an increase in amino and organic acids reaching their maximum levels after 48 (1.3-fold) and 72 (1.7-fold) h, respectively. In addition, phenolic acids (e.g., sagerinic acid, rosmarinic acid, and 3-O-methylrosmarinic acid) followed by flavonoid aglycones (e.g., salvigenin and 5,6,4'-trihydroxy-7,3'-dimethoxyflavone) were the most abundant with prominent increases at 48 (1.2-fold) and 72 (2.1-fold) h, respectively. The aroma was intensified by the elicitation along the time, especially after 48 and 72 h. Furthermore, multivariate data analyses, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) confirmed elicitation effect, especially post 48 and 72 h. The study further assessed the effect of MeJA elicitation on the antioxidant and polyphenolic content. The cultures at 48 h demonstrated a significant (p < 0.05) antioxidant activity concurrently with correlation with total polyphenolic content using Pearson's correlation. Our study provides new insights to the elicitation impact on primary and secondary metabolism, in addition to aroma profile, to orchestrate the stress response and in relation to antioxidant effect.PMID:37385363 | DOI:10.1016/j.phytochem.2023.113777

Food Chem Toxicol. 2023 Jun 27:113908. doi: 10.1016/j.fct.2023.113908. Online ahead of print.ABSTRACTTriclocarban (TCC) is an antibacterial component widely used in personal care products with potential toxicity possessing public health issues. Unfortunately, enterotoxicity mechanisms of TCC exposure remain largely unknown. Using a combination of 16S rRNA gene sequencing, metabolomics, histopathological and biological examinations, this study systematically explored the deteriorating effects of TCC exposure on a dextran sulfate sodium (DSS)-induced colitis mouse model. We found that TCC exposure at different doses significantly aggravated colitis phenotypes including shortened colon length and altered colonic histopathology. Mechanically, TCC exposure further disrupted intestinal barrier function, manifested by significant downregulation of the number of goblet cells, mucus layer thickness and expression of junction proteins (MUC-2, ZO-1, E-cadherin and Occludin). The gut microbiota composition and its metabolites such as short-chain fatty acids (SCFAs) and tryptophan metabolites were also markedly altered in DSS-induced colitis mice. Consequently, TCC exposure markedly exacerbated colonic inflammatory status of DSS-treated mice by activating NF-κB pathway. These findings provided new evidence that TCC could be an environmental hazards for development of IBD or even colon cancer.PMID:37385329 | DOI:10.1016/j.fct.2023.113908