PubMed

Phytother Res. 2022 Nov 25. doi: 10.1002/ptr.7673. Online ahead of print.ABSTRACTEuphorbia pekinensis (EP) is a commonly used Chinese medicine treating edema with potential hepatorenal toxicity. However, its toxic mechanism and prevention are remained to be explored. Oleanolic acid (OA) is a triterpene acid with potential hepatorenal protective activities. We investigated the protective effect and potential mechanism of OA on EP-induced hepatorenal toxicity. In this study, rats were given total diterpenes from EP (TDEP, 16 mg/kg) combined with OA (10, 20, 40 mg/kg) by gavage for 4 weeks. The results showed that TDEP administration could lead to a 3-4-fold increasement in hepatorenal biochemical parameters with histopathological injuries, while OA treatment could ameliorate them in a dose-dependent manner. At microbial and metabolic levels, intestinal flora and host metabolism were perturbed after TDEP administration. The disturbance of bile acid metabolism was the most significant metabolic pathway, with secondary bile acids increasing while conjugated bile acids decreased. OA treatment can improve the disorder of intestinal flora and metabolic bile acid spectrum. Further correlation analysis screened out that Escherichia-Shigella, Phascolarctobacterium, Acetatifactor, and Akkermansia were closely related to the bile acid metabolic disorder. In conclusion, oleanolic acid could prevent hepatorenal toxicity induced by EP by regulating bile acids metabolic disorder via intestinal flora improvement.PMID:36426741 | DOI:10.1002/ptr.7673

J Exp Biol. 2022 Nov 25:jeb.244795. doi: 10.1242/jeb.244795. Online ahead of print.ABSTRACTOrganisms can faster and more efficiently modify and increase their thermal tolerance after a brief exposure to sublethal thermal stress. This response is called "heat-hardening" as it leads to the generation of phenotypes with increased heat tolerance. The aim of the study was to investigate the impact of heat-hardening on the metabolomic profile of M. galloprovincialis in order to identify the undergoing adjustments of biochemical pathways that might benefit mussels' thermal tolerance. Thus, mussels were exposed sequentially to two different phases (heat-hardening and acclimation phases). To gain further insights into the possible mechanisms underlying the metabolic response of the heat-hardened M. galloprovincialis, metabolomics analysis was complemented by the estimation of mRNA expression of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate kinase (PK) and alternative oxidase (AOX) implicated in the metabolic pathways of gluconeogenesis, glycolysis and redox homeostasis, respectively. Heat-hardened mussels showed evidence of higher activity of tricarboxylic acid (TCA) cycle and diversification of upregulated metabolic pathways, possibly as a mechanism to increase ATP production and extend survival under heat stress. Moreover, formate and taurine accumulation provide an antioxidant and cytoprotective role in mussels during hypoxia and thermal stress. Overall, the metabolic responses in non- and heat-hardened mussels underline the upper thermal limits of M. galloprovincialis, set at 26°C, and are in accordance with the OCLTT concept. The ability of heat-hardened mussels for a rapid gain and slow loss of heat tolerance may be an advantageous strategy for coping with the intermittent, and often extreme temperatures.PMID:36426666 | DOI:10.1242/jeb.244795

J Sci Food Agric. 2022 Nov 25. doi: 10.1002/jsfa.12355. Online ahead of print.ABSTRACTBACKGROUND: Soybean (Glycine max) is high in proteins and isoflavones that offer many benefits to human health, while the fermentation process suggested enhancing the nutrients of the soybeans. Organic foods are perceived as better than non-organic in terms of health benefits, yet little is known about the difference in the phytochemical contents that discriminate the quality of organic from non-organic soybeans. In this study, the chemical profiles of non-organic (G, T, U, UB) and organic (C, COF, A, R, B, Z) soybeans (Glycine max [L.] Merr.) and their metabolite changes after fermentation with Rhizopus oligosporus were investigated.RESULTS: A clear separation was only observed between non-organic G and organic Z which were then selected for further investigation in the fermentation of soybeans (GF and ZF). All four groups (G, Z, GF, ZF) were analyzed using NMR along with LC-MS/MS, wherein a total of 41 and 47 metabolites were identified respectively, with 12 in common. A clear variation (|log1.5 FC| > 2 and p < 0.05) was observed between Z and ZF, whereby most of the sugars and isoflavone glycosides are found only in Z, while more amino acids and organic acids are found in ZF. Additional four metabolites clustered as C-glycosylflavonoids were discovered from MS/MS-based molecular networking.CONCLUSION: Chemical profiles of non-organic and organic soybeans exhibited no significant difference. However, the metabolites profile of the unfermented soybean that is higher in sugars shifted to higher amino acids and organic acids after fermentation, thereby potentially enhancing their nutritional value. This article is protected by copyright. All rights reserved.PMID:36426592 | DOI:10.1002/jsfa.12355

Eur J Ophthalmol. 2022 Nov 25:11206721221140948. doi: 10.1177/11206721221140948. Online ahead of print.ABSTRACTPURPOSE: This review focuses on utility of artificial intelligence (AI) in analysis of biofluid markers in glaucoma. We detail the accuracy and validity of AI in the exploration of biomarkers to provide insight into glaucoma pathogenesis.METHODS: A comprehensive search was conducted across five electronic databases including Embase, Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science. Studies pertaining to biofluid marker analysis using AI or bioinformatics in glaucoma were included. Identified studies were critically appraised and assessed for risk of bias using the Joanna Briggs Institute Critical Appraisal tools.RESULTS: A total of 10,258 studies were screened and 39 studies met the inclusion criteria, including 23 cross-sectional studies (59%), nine prospective cohort studies (23%), six retrospective cohort studies (15%), and one case-control study (3%). Primary open angle glaucoma (POAG) was the most commonly studied subtype (55% of included studies). Twenty-four studies examined disease characteristics, 10 explored treatment decisions, and 5 provided diagnostic clarification. While studies examined at entire metabolomic or proteomic profiles to determine changes in POAG, there was heterogeneity in the data with over 175 unique, differentially expressed biomarkers reported. Discriminant analysis and artificial neural network predictive models displayed strong differentiating ability between glaucoma patients and controls, although these tools were untested in a clinical context.CONCLUSION: The use of AI models could inform glaucoma diagnosis with high sensitivity and specificity. While insight into differentially expressed biomarkers is valuable in pathogenic exploration, no clear pathogenic mechanism in glaucoma has emerged.PMID:36426575 | DOI:10.1177/11206721221140948

Allergy Asthma Immunol Res. 2022 Nov;14(6):713-729. doi: 10.4168/aair.2022.14.6.713.ABSTRACTPURPOSE: Studies have shown that Mycoplasma pneumoniae (Mp) infection can aggravate symptoms in asthmatics. However, the mechanism by which Mp infection exacerbates asthma remains unclear. Metabolomics can help identify the mechanism of Mp aggravating asthma in children, thereby providing more a potential target for improving clinical treatment programs. In this article, we analyzed the metabolic level of patients to explain how Mp aggravates asthma in children.METHODS: We divided the subjects into the asthma, Mp infection, asthma combined with Mp infection and healthy groups. Patients' peripheral blood was collected for metabolic and interaction analysis. Cytokine levels were measured via serum and exhaled breath condensate (EBC).RESULTS: A total of 150 participating subjects were divided into four groups after exclusion. We found out that there were different metabolic pathways between the healthy and disease groups. The major pathways of both asthma and asthma combined with Mp infection were valine, leucine and isoleucine biosynthesis; malate-aspartate shuttle was the main differential pathway for Mp infection. Moreover, even though three disease groups involved 81 metabolites at the same time, compared with asthma combined with Mp infection, 2 single disease groups still involved different amino acid pathways (phenylalanine, tyrosine and tryptophan biosynthesis; valine, leucine and isoleucine biosynthesis). Interaction analysis showed that Mp infection in asthmatic patients not only activated cytokines, but also activated Toll-like receptors (TLRs) 2 and 6. Finally, the levels of interleukin (IL)-4, IL-8, IL-13 and tumor necrosis factor-α in EBC with asthma combined with Mp infection were significantly higher than the 2 single disease groups.CONCLUSIONS: Mp infection in asthmatic children can cause changes in the levels of various amino acids in the body, which were enriched in the pathways such as valine, leucine and isoleucine biosynthesis. Palmitic acid can activate TLR2, and iloprost reduces IL-10 levels, ultimately leading to the increased airway inflammation.PMID:36426399 | DOI:10.4168/aair.2022.14.6.713

Front Plant Sci. 2022 Nov 8;13:970496. doi: 10.3389/fpls.2022.970496. eCollection 2022.ABSTRACTCold and drought stress are the two most severe abiotic stresses in alpine regions. Poa crymophila is widely grown in the Qinghai-Tibet Plateau with strong tolerance. Here, by profiling gene expression patterns and metabolomics-associated transcriptomics co-expression network, the acclimation of Poa crymophila to the two stresses was characterized. (1) The genes and metabolites with stress tolerance were induced by cold and drought, while those related with growth were inhibited, and most of them were restored faster after stresses disappeared. In particular, the genes for the photosynthesis system had strong resilience. (2) Additionally, cold and drought activated hypoxia and UV-B adaptation genes, indicating long-term life on the plateau could produce special adaptations. (3) Phenolamines, polyamines, and amino acids, especially N',N″,N'″-p-coumaroyl-cinnamoyl-caffeoyl spermidine, putrescine, and arginine, play key roles in harsh environments. Flexible response and quick recovery are strategies for adaptation to drought and cold in P. crymophila, accounting for its robust tolerance and resilience. In this study, we presented a comprehensive stress response profile of P. crymophila and provided many candidate genes or metabolites for future forage improvement.PMID:36426156 | PMC:PMC9681527 | DOI:10.3389/fpls.2022.970496

Front Plant Sci. 2022 Nov 8;13:1009956. doi: 10.3389/fpls.2022.1009956. eCollection 2022.ABSTRACTSoil biosolarization (SBS) is an alternative technique for soil pest control to standard techniques such as soil fumigation and soil solarization (SS). By using both solar heating and fermentation of organic amendments, faster and more effective control of soilborne pathogens can be achieved. A circular economy may be created by using the residues of a given crop as organic amendments to biosolarize fields that produce that crop, which is termed circular soil biosolarization (CSBS). In this study, CSBS was employed by biosolarizing soil with amended tomato pomace (TP) residues and examining its impact on tomato cropping under conditions of abiotic stresses, specifically high salinity and nitrogen deficiency. The results showed that in the absence of abiotic stress, CSBS can benefit plant physiological performance, growth and yield relative to SS. Moreover, CSBS significantly mitigated the impacts of abiotic stress conditions. The results also showed that CSBS impacted the soil microbiome and plant metabolome. Mycoplana and Kaistobacter genera were found to be positively correlated with benefits to tomato plants health under abiotic stress conditions. Conversely, the relative abundance of the orders RB41, MND1, and the family Ellin6075 and were negatively correlated with tomato plants health. Moreover, several metabolites were significantly affected in plants grown in SS- and CSBS-treated soils under abiotic stress conditions. The metabolite xylonic acid isomer was found to be significantly negatively correlated with tomato plants health performance across all treatments. These findings improve understanding of the interactions between CSBS, soil ecology, and crop physiology under abiotic stress conditions.PMID:36426148 | PMC:PMC9679285 | DOI:10.3389/fpls.2022.1009956

Front Plant Sci. 2022 Nov 8;13:1057226. doi: 10.3389/fpls.2022.1057226. eCollection 2022.ABSTRACTThe apple is an economically important fruit, and fruit russeting is not conducive to its appearance. Although studies have examined fruit russeting, its mechanism remains unclear. Two apple strains of the F1 hybrid population derived from 'Fuji' and 'Golden Delicious' were used in this study. We found that the skin of russet apples was rough and fissured, while that of non-russet apples was smooth and waxy. Chemical staining, LC- and GC-MS showed that both lignin and suberin were increased in russet apple skin. Meanwhile, genes involved in lignin and suberin synthetic pathways were upregulated in russet apple skin. Additionally, we found many differentially expressed genes (DEGs1) involved in hormone biosynthesis and signaling and stress responses in the two apple strains. We found that WRKY13 may influence russeting by regulating lignin synthesis. Our study identified several candidate metabolites and genes, which will provide a good foundation for further research.PMID:36426145 | PMC:PMC9678910 | DOI:10.3389/fpls.2022.1057226

Front Pharmacol. 2022 Nov 8;13:1048728. doi: 10.3389/fphar.2022.1048728. eCollection 2022.ABSTRACTValproic acid (VPA) is widely used as a major drug in the treatment of epilepsy. Despite the undisputed pharmacological importance and effectiveness of VPA, its potential hepatotoxicity is still a major concern. Being a simple fatty acid, the hepatotoxicity induced by VPA has long been considered to be due primarily to its interference with fatty acid β-oxidation (β-FAO). The aim of this study was to investigate the biomarkers for VPA-induced abnormal liver function in epileptic children and to determine potential mechanisms of its liver injury. Targeted metabolomics analysis of acylcarnitines (ACs) was performed in children's serum. Metabolomic analysis revealed that VPA -induced abnormal liver function resulted in the accumulation of serum long-chain acylcarnitines (LCACs), and the reduced expression of β-FAO relevant genes (Carnitine palmitoyltrans-ferase (CPT)1, CPT2 and Long-chain acyl-CoA dehydrogenase (LCAD)), indicating the disruption of β-FAO. As direct peroxisome proliferator-activated receptor a (PPARα)- regulated genes, CPT1A, CPT2 and LCAD were up-regulated after treatment with PPARα agonist, fenofibrate (Feno), indicating the improvement of β-FAO. Feno significantly ameliorated the accumulation of various lipids in the plasma of VPA-induced hepatotoxic mice by activating PPARα, significantly reduced the plasma ACs concentration, and attenuated VPA-induced hepatic steatosis. Enhanced oxidative stress and induced by VPA exposure were significantly recovered using Feno treatment. In conclusion, this study indicates VPA-induced β-FAO disruption might lead to liver injury, and a significant Feno protective effect against VPA -induced hepatotoxicity through reversing fatty acid metabolism.PMID:36425583 | PMC:PMC9681037 | DOI:10.3389/fphar.2022.1048728

RSC Adv. 2022 Nov 16;12(51):32844-32852. doi: 10.1039/d2ra04600h. eCollection 2022 Nov 15.ABSTRACTThe COVID-19 pandemic caused a huge health crisis all over the globe. SARS-CoV-2 is the virus responsible for the disease and it is highly contagious leaving millions of confirmed infected cases and a dangerous death toll. Carica papaya is a tropical plant known for its antiviral activity since it possesses different classes of compounds that are believed to combat various viral classes. In this study, the extracts prepared from C. papaya leaves cultivated in Egypt were evaluated for their anti-SARS-CoV-2 activity using crystal violet assay and for their cytotoxicity through MTT assay. The total methanolic extract, n-hexane, ethyl acetate, and n-butanol fractions of papaya leaves were used in the study and the results revealed that the n-hexane fraction has a high anti-SARS-CoV-2 activity with an IC50 value = 1.98 μg mL-1. Moreover, it also showed a high selectivity index value = 104.7. Dereplication of the secondary metabolites in the crude methanolic extract of C. papaya leaves revealed the presence of different classes of compounds including sterols, terpenes, fatty acid, alkaloids and flavonoids that are known to possess antiviral activities against various classes of viruses. The current study was assisted by molecular docking, molecular dynamics simulation and MM-PBSA calculations for the annotated compounds against 6 SARS-CoV-2 target proteins. The results of these in silico-based investigations showed high to moderate binding on the targeted proteins. This postulation may instigate further research studies concerning the compounds responsible for this high anti-SARS-CoV-2 activity of the n-hexane fraction of C. papaya leaves.PMID:36425179 | PMC:PMC9667237 | DOI:10.1039/d2ra04600h

Front Nutr. 2022 Nov 8;9:1035788. doi: 10.3389/fnut.2022.1035788. eCollection 2022.ABSTRACTThis study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. The content of total flavonoids and polysaccharides reached 78.65 ± 0.82 μg/mL and 9358.08 ± 122.96 μg/mL, respectively. In addition, ABTS+, DPPH⋅, and ⋅OH clearance rates reached 95.09, 88.85, and 85.36% at 24 h under optimized conditions, respectively. The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. Simultaneously, 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates were observed, respectively. Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials.PMID:36424929 | PMC:PMC9679022 | DOI:10.3389/fnut.2022.1035788

Eur Heart J. 2022 Nov 25:ehac616. doi: 10.1093/eurheartj/ehac616. Online ahead of print.NO ABSTRACTPMID:36424762 | DOI:10.1093/eurheartj/ehac616

Eur Heart J. 2022 Nov 25:ehac446. doi: 10.1093/eurheartj/ehac446. Online ahead of print.ABSTRACTAIMS: Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood.METHODS AND RESULTS: In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008], with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study.CONCLUSION: Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.PMID:36424694 | DOI:10.1093/eurheartj/ehac446

Sci Rep. 2022 Nov 23;12(1):20168. doi: 10.1038/s41598-022-24382-4.ABSTRACTEnterococci are a common cause of urinary tract infections. The severity of enterococcal infections is associated with their ability to form biofilms. Morus leaves are known as a natural antibacterial, however, their antibiofilm activity against Enterococcus remains unveiled. This study aimed to evaluate the ability of four polyphenol-rich Morus leaves extracts (Morus nigra, M. rubra, M. macroura, and M. alba) to inhibit biofilm formed by enterococcal clinical isolates in relation to their metabolic profiling. Results revealed that 48% of the isolates formed strong biofilm, 28% formed moderate biofilm, 20% formed weak biofilm, and only 4% did not form a biofilm. The strong biofilm-forming isolates were E. faecalis, and hence were chosen for this study. The antibiofilm activity of the four polyphenol-rich Morus leaves extracts revealed that the M. nigra extract exhibited the highest percentage of biofilm inhibition followed by M. rubra then M. macroura and the least inhibition was detected in M. alba, and these results were in accordance with the phenolic and flavonoid contents of each extract. UPLC-ESI-MS/MS identified 61 polyphenolic compounds in the four extracts. Further, multivariate analysis confirmed clear segregation of M. nigra from the other species suggesting disparity in its metabolome, with accumulation of flavonoids, anthocyanidins, phenolic acids and coumarin derivatives. Quercetin and kaempferol glycosides were found to be positively and significantly correlated to the antibiofilm activity. In conclusion, M. nigra ethanolic extracts showed the highest phenolic content and antibiofilm activity and they could be developed as a complementary treatment for the development of antimicrobial agents.PMID:36424446 | DOI:10.1038/s41598-022-24382-4

Sci Rep. 2022 Nov 23;12(1):20161. doi: 10.1038/s41598-022-24687-4.ABSTRACTBioreactors are one of the most important, basic pieces of equipment in the biopharmaceutical industry. Understanding the effects of mechanical damage and other factors on the physiological state of cells during cell matrix culture is the basis for continuously achieving greater efficiency and higher product quality. In this study, Vero cells were used as a model and apoptosis, senescence, transcriptomics, proteomics, and metabolomics were carried out for analysis at the cellular and molecular levels. The results showed that compared with cells cultured in the simulated natural state, the cells cultured in the basket bioreactor displayed no obvious senescence. Additionally, the proportion of early apoptotic cells increased, but the proportions of damaged, late apoptotic and dead cells did not change significantly. The transcription levels of aminoacyl-tRNA synthetase and cyclin D1 and the expression levels of DNA replication licensing factor, methenyltetrahydrofolate cyclohydrolase, arachidonic acid and other metabolites of cells cultured in the basket bioreactor were significantly increased. These results suggest that DNA replication, protein translation and the metabolic activities in cells cultured in basket bioreactors are more active, which is more conducive to cell amplification and target product production. In this study, the growth and physiological state of cells in a basket bioreactor were characterized at the molecular level for the first time. Additionally, a tool to evaluate the physiological state of cells in a bioreactor was established, which can be used to guide the development and optimization of cell matrix culture conditions in industrial production and improve the production efficiency of the target products.PMID:36424406 | DOI:10.1038/s41598-022-24687-4

Hum Immunol. 2022 Nov 21:S0198-8859(22)00232-4. doi: 10.1016/j.humimm.2022.11.004. Online ahead of print.ABSTRACTAlthough decades of the reductionist approach achieved great milestones in optimizing the immunosuppression therapy, traditional clinical parameters still fail in predicting both acute and chronic (mainly) rejection events leading to higher rates across all solid organ transplants. To clarify the underlying immune-related cellular and molecular mechanisms, current biomedical research is increasingly focusing on "transplantomics" which relies on a huge quantity of big data deriving from genomics, transcriptomics, epigenomics, proteomics, and metabolomics platforms. The AlloMap (gene expression) and the AlloSure (donor-derived cell-free DNA) tests represent two successful examples of how omics and liquid biopsy can really improve the precision medicine of heart and kidney transplantation. One of the major challenges in translating big data in clinically useful biomarkers is the integration and interpretation of the different layers of omics datasets. Network Medicine offers advanced bioinformatic-molecular strategies which were widely used to integrate large omics datasets and clinical information in end-stage patients to prioritize potential biomarkers and drug targets. The application of network-oriented approaches to clarify the complex nature of graft rejection is still in its infancy. Here, we briefly discuss the real-life clinical applications derived from omics datasets as well as novel opportunities for establishing predictive tests in solid organ transplantation. Also, we provide an original "graft rejection interactome" and propose network-oriented strategies which can be useful to improve precision medicine of solid organ transplantation.PMID:36424231 | DOI:10.1016/j.humimm.2022.11.004

Environ Pollut. 2022 Nov 21:120701. doi: 10.1016/j.envpol.2022.120701. Online ahead of print.ABSTRACTStudies exploring the association of tetrabromobisphenol A (TBBPA) with breast cancer and related mechanisms are limited. To investigate the relationship between TBBPA levels in breast adipose and breast cancer, we carried out case-control research. As well as further examine the mediating role of adipose metabolites between TBBPA and breast cancer using the metabolomics approach. In this study, the concentration of TBBPA was determined utilizing ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after a solid phase extraction (SPE) pretreatment. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was employed to analyze adipose metabolomics. Evaluation of metabolites linked to TBBPA exposure and breast cancer was performed utilizing mediation analysis. With an estimated OR (95%CI) of 1.153 (1.023, 1.299), TBBPA was firmly linked with breast cancer. We also used propensity score matching analysis and sensitivity analysis to reduce the effect of confounding factors on the results. Metabolomics of adipose suggested significant perturbation in the linoleic acid metabolism pathway. In addition, for PC (16:0/16:0) as phospholipids, a mediation effect on the associations of TBBPA exposure with breast cancer risks was observed (estimated mediation percentage: 56.58%). Understanding the relationship between TBBPA exposure and the risk of breast cancer may be facilitated by the findings, which point to potential mediation metabolites.PMID:36423888 | DOI:10.1016/j.envpol.2022.120701

Pharmacol Res. 2022 Nov 21:106570. doi: 10.1016/j.phrs.2022.106570. Online ahead of print.ABSTRACTHypercholesterolemia is a major driver of atherosclerosis, thus contributing to high morbidity and mortality worldwide. Gut microbiota have been identified as modulator of blood lipids including cholesterol levels. Few studies have already linked certain bacteria and microbial mechanisms to host cholesterol. However, in particular mouse models revealed conflicting results depending on genetics and experimental protocol. To gain further insights into the relationship between intestinal bacteria and host cholesterol metabolism, we first performed fecal 16S rRNA targeted metagenomic sequencing in a human cohort (n = 24) naïve for cholesterol lowering drugs. Here, we show alterations in the gut microbiota composition of hypercholesterolemic patients with depletion of Bifidobacteria, expansion of Clostridia and increased Firmicutes/Bacteroidetes ratio. To test whether pharmacological intervention in gut microbiota impacts host serum levels of cholesterol, we treated hypercholesterolemic Apolipoprotein E knockout with oral largely non-absorbable antibiotics. Antibiotics increased serum cholesterol, but only when mice were fed normal chow diet and cholesterol was measured in the random fed state. These elevations in cholesterol already occurred few days after treatment initiation and were reversible after stopping antibiotics with re-acquisition of intestinal bacteria. Gene expression analyses pointed to increased intestinal cholesterol uptake mediated by antibiotics in the fed state. Non-targeted serum metabolomics suggested that diminished plant sterol levels and reduced bile acid cycling were involved microbial mechanisms. In conclusion, our work further enlightens the link between gut microbiota and host cholesterol metabolism. Pharmacological disruption of the gut flora by antibiotics was able to exacerbate serum cholesterol and may impact cardiovascular disease.PMID:36423788 | DOI:10.1016/j.phrs.2022.106570

Bioresour Technol. 2022 Nov 21:128370. doi: 10.1016/j.biortech.2022.128370. Online ahead of print.ABSTRACTAstaxanthin is used extensively in the nutraceutical, aquaculture, and cosmetic industries. The current market necessitates higher astaxanthin production from Phaffia rhodozyma (P. rhodozyma) due to its higher cost compared to chemical synthesis. In this study, a bubble discharge reactor was developed to generate plasma-activated water (PAW) to produce PAW-made yeast malt (YM) medium. Due to oxidative stress induced by PAW, strains cultured in 15 and 30 min-treated PAW-made medium produced 7.9±1.2% and 12.6±1.4% more carotenoids with 15.5±3.3% and 22.1±1.3% more astaxanthin, respectively. Reactive oxygen species (ROS) assay results showed that ROS generated by plasma-water interactions elevated intracellular ROS levels. Proteomic analysis revealed increased expression of proteins involved in the cellular response to oxidative stress as well as carotenoid biosynthesis, both of which contribute to higher yields of astaxanthin. Overall, this study supports the potential of PAW to increase astaxanthin yields for industrial-scale production.PMID:36423765 | DOI:10.1016/j.biortech.2022.128370

J Pharm Biomed Anal. 2022 Nov 14;224:115162. doi: 10.1016/j.jpba.2022.115162. Online ahead of print.ABSTRACTThis work reports on targeted UHPLC-tandem mass spectrometry methods for the chiral separation of anteiso-methyl branched fatty acids (aiFAs). The methods involve precolumn derivatization with 1-naphthylamine and chiral separation on Chiralpak IG-U. anteiso-Methyl branched fatty acids with up to eight carbons can be separated. A method was used for the assignment of the absolute configuration of an aiFA present as fatty acyl residue of the teicoplanin mixture, namely teicoplanin RS3. Furthermore, the excellent methylene selectivity and improved selectivity for constitutional isomers of the polysaccharide columns was exploited for the elucidation and structural confirmation of previously unknown fatty acyl residues in teicoplanin. This shows the versatility and practical applicability of polysaccharide columns as orthogonal stationary phases to reversed-phase for structural elucidation of natural compounds. The developed methods are useful tools for related subdisciplines such as targeted metabolomics and lipidomics.PMID:36423498 | DOI:10.1016/j.jpba.2022.115162