PubMed

Sci Total Environ. 2022 Nov 22:160387. doi: 10.1016/j.scitotenv.2022.160387. Online ahead of print.ABSTRACTMicroplastic contamination of freshwater ecosystems has become an increasing environmental concern. To advance the hazard assessment of microplastics, we conducted a microcosm experiment in which we exposed a simplified aquatic ecosystem consisting of moss and caddisflies to microplastics (polyethylene, polystyrene and polypropylene) and pharmaceuticals and personal care products (1H-benzotriazole, bisphenol A, caffeine, gemfibrozil, ketoprofen, methylparaben, estriol, diphenhydramine, tris (1-chloro-2-propyl) phosphate) over the course of 60 days. We monitored the flux of microplastics within the microcosm, as well as the metabolic and total protein variation of organisms. This study offers evidence highlighting the capacity of moss to act as a sink for free-floating microplastics in freshwater environments. Moss is also shown to serve as a source and pathway for microplastic particles to enter aquatic food webs via caddisflies feeding off of the moss. Although most ingested microparticles were eliminated between caddisflies life stages; however, a small fraction of microplastics was transferred from aquatic to terrestrial ecosystem by emergence. While moss exhibited a mild response to microplastic stress, caddisflies ingesting microplastics showed stress comparable to that caused by exposure to pharmaceuticals. The molecular responses that the stressors triggered were tentatively identified and related to phenotypic responses such as the delayed development manifested through the delayed emergence of caddisflies exposed to stress. Overall, our study provides valuable insights into the adverse effects of microplastics on aquatic species, compares the impacts of microplastics on freshwater biota to those of pharmaceuticals and endocrine disrupting compounds, and demonstrates the role aquatic organisms have in redistributing microplastics between aquatic and terrestrial ecosystems.PMID:36427730 | DOI:10.1016/j.scitotenv.2022.160387

Water Res. 2022 Nov 17;228(Pt A):119377. doi: 10.1016/j.watres.2022.119377. Online ahead of print.ABSTRACTAdaptation to substrate fluctuations is a life actuality of microbes in global municipal wastewater treatment plants (WWTPs). Yet there remains a lack of definite information on how influent changes with different alternation frequencies shape the stability of anammox consortia and the metabolic regulations they feedback. According to human rhythmic activity, day-fluctuant fed (every 6 h, alternating between 50 and 100 mg NH4+-N/L) substantially diminished the robustness of nitrogen removal efficiency (NRE; 84.1 ± 7.0%, left-skewed distribution [R2 = 0.87]) and shock-resistance ability (>30% effluent variability). Unexpectedly, the anammox ecosystem under week-fluctuant mode (every 6 d) displayed adapted growth (NRE 86.6 ± 3.1%, normal distribution [R2 = 0.97]), higher extracellular polymeric substances (EPS) yields, and superior tolerance (juggling the shortest recovery time and highest NRE, tightest protein secondary structure facing long-term load shocks) than steady-state (75 mg NH4+-N/L). 16S sequencing showed that the influent disturbance led to increased levels of bacterial diversity, however, a similar microbiota composition between week-fluctuant and steady systems was detected. Notably, K strategist Candidatus Kuenenia was more sensitive to substrate fluctuations, with the lower relative abundance at day-fluctuant (23.4 ± 5.1%) and week-fluctuant (39.5 ± 4.3%) than at steady-state community (47.5 ± 4.2%). Conversely, Candidatus Jettenia had higher relative abundance at day-fluctuant (i.e., 1.3 ± 0.1%) compared to that at week-fluctuant (0.2 ± 0.04%) and steady-state (0.05 ± 0.03%). Importantly, untargeted metabolomics revealed that week-fluctuant grown anammox microbiota increased protein synthesis and transporter expression while decreasing expression of catabolic pathways (citric acid cycle and bypass) as a strategy for efficient substrate uptake and utilization, which clearly different to day-fluctuant and steady-state survival ways. Overall, we predictively reported an "anabolic adaptation growth state" for the anammox consortia and put forward the associated reinforcement control strategy.PMID:36427463 | DOI:10.1016/j.watres.2022.119377

Sci Immunol. 2022 Nov 25;7(77):eabl9467. doi: 10.1126/sciimmunol.abl9467. Epub 2022 Nov 25.ABSTRACTActivated lymphocytes adapt their metabolism to meet the energetic and biosynthetic demands imposed by rapid growth and proliferation. Common gamma chain (cγ) family cytokines are central to these processes, but the role of downstream signal transducer and activator of transcription 5 (STAT5) signaling, which is engaged by all cγ members, is poorly understood. Using genome-, transcriptome-, and metabolome-wide analyses, we demonstrate that STAT5 is a master regulator of energy and amino acid metabolism in CD4+ T helper cells. Mechanistically, STAT5 localizes to an array of enhancers and promoters for genes encoding essential enzymes and transporters, where it facilitates p300 recruitment and epigenetic remodeling. We also find that STAT5 licenses the activity of two other key metabolic regulators, the mTOR signaling pathway and the MYC transcription factor. Building on the latter, we present evidence for transcriptome-wide cooperation between STAT5 and MYC in both normal and transformed T cells. Together, our data provide a molecular framework for transcriptional programing of T cell metabolism downstream of cγ cytokines and highlight the JAK-STAT pathway in mediating cellular growth and proliferation.PMID:36427325 | DOI:10.1126/sciimmunol.abl9467

Hum Reprod. 2022 Nov 25:deac254. doi: 10.1093/humrep/deac254. Online ahead of print.ABSTRACTSTUDY QUESTION: Can a combination of metabolomic signature and machine learning (ML) models distinguish nonclassic 21-hydroxylase deficiency (NC21OHD) from polycystic ovary syndrome (PCOS) without adrenocorticotrophic hormone (ACTH) testing?SUMMARY ANSWER: A single sampling methodology may be an alternative to the dynamic ACTH test in order to exclude the diagnosis of NC21OHD in the presence of a clinical hyperandrogenic presentation at any time of the menstrual cycle.WHAT IS KNOWN ALREADY: The clinical presentation of patients with NC21OHD is similar with that for other disorders of androgen excess. Currently, cosyntropin stimulation remains the gold standard diagnosis of NC21OHD.STUDY DESIGN, SIZE, DURATION: The study was designed using a bicentric recruitment: an internal training set included 19 women with NC21OHD and 19 controls used for developing the model; a test set included 17 NC21OHD, 72 controls and 266 PCOS patients used to evaluate the performance of the diagnostic strategy thanks to an ML approach.PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifteen steroid species were measured in serum by liquid chromatography-mass spectrometry (LC-MS/MS). This set of 15 steroids (defined as 'steroidome') used to map the steroid biosynthesis pathway was the input for our models.MAIN RESULTS AND THE ROLE OF CHANCE: From a single sample, modeling involving metabolic pathway mapping by profiling 15 circulating steroids allowed us to identify perfectly NC21OHD from a confounding PCOS population. The constructed model using baseline LC-MS/MS-acquired steroid fingerprinting successfully excluded all 17 NC21OHDs (sensitivity and specificity of 100%) from 266 PCOS from an external testing cohort of originally 549 women, without the use of ACTH testing. Blood sampling timing during the menstrual cycle phase did not impact the efficiency of our model.LIMITATIONS, REASONS FOR CAUTION: The main limitations were the use of a restricted and fully prospective cohort as well as an analytical issue, as not all laboratories are equipped with mass spectrometers able to routinely measure this panel of 15 steroids. Moreover, the robustness of our model needs to be established with a larger prospective study for definitive validation in clinical practice.WIDER IMPLICATIONS OF THE FINDINGS: This tool makes it possible to propose a new semiology for the management of hyperandrogenism. The model presents better diagnostic performances compared to the current reference strategy. The management of patients may be facilitated by limiting the use of ACTH tests. Finally, the modeling process allows a classification of steroid contributions to rationalize the biomarker approach and highlight some underlying pathophysiological mechanisms.STUDY FUNDING/COMPETING INTEREST(S): This study was supported by 'Agence Française de Lutte contre le dopage' and DIM Région Ile de France. This study was supported by the French institutional PHRC 2010-AOR10032 funding source and APHP. All authors declare no competing financial interests.TRIAL REGISTRATION NUMBER: N/A.PMID:36427016 | DOI:10.1093/humrep/deac254

ACS Appl Bio Mater. 2022 Nov 25. doi: 10.1021/acsabm.2c00857. Online ahead of print.ABSTRACTUnder healthy physiological conditions, living organisms possess a variety of antioxidant mechanisms to scavenge overproduced reactive oxygen species (ROS). However, under pathological circumstances, endogenous antioxidant systems may not be adequate to eliminate the excessive amount of oxidants, and thus, a continuous exogenous antioxidant income is required. In this regard, sumac (Rhus coriaria) extract is a good candidate for therapeutic applications, because of its high content of antioxidant polyphenolic compounds. In this work, sumac extract-loaded nanosheets (sumac-nanosheet) have been exploited for loading and controlled release of sumac extract, envisioning topical drug delivery applications. Sumac extract has been obtained through the solvent extraction method, and polymeric nanosheets have been thereafter prepared through the spin coating-assisted layer-by-layer deposition of polycaprolactone (PCL), sumac extract, and poly(d,l-lactic acid) (PDLLA). The collected data show a rich content of the sumac extract in terms of polyphenolic compounds, as well as its strong antioxidant properties. Moreover, for the first time in the literature, we demonstrated the possibility of efficiently loading such extract in polymeric nanosheets and the suitability of this nanoplatform as a reactive oxygen species scavenger in human dermal fibroblasts treated with a pro-oxidant insult.PMID:36426992 | DOI:10.1021/acsabm.2c00857

Mol Omics. 2022 Nov 25. doi: 10.1039/d2mo00260d. Online ahead of print.ABSTRACTAtherosclerosis is the principal cause of vascular diseases and one of the leading causes of worldwide death. Even though several insights into its natural course, risk factors and interventions have been identified, it is still an ongoing global pandemic. Since the structure and biochemical composition of the plaques show high heterogeneity, a comprehensive understanding of the intraplaque composition, its microenvironment, and the mechanisms of the progression and instability across different vascular beds at their progression stages is crucial for better risk stratification and treatment modalities. Even though several cell-based studies, animal studies, and extensive multicentric population studies have been conducted concerning cardiovascular diseases for assessing the risk factors and plaque biology, the studies on human clinical samples are very limited. New novel approaches utilize samples from percutaneous coronary interventions, which could possibly gain more access to clinical samples at different stages of the diseases without complex invasive resections. As an emerging technological platform in disease discovery research, mass spectrometry-based omics technologies offer capabilities for a comprehensive understanding of the mechanisms linked to several vascular diseases. Here, we discuss the cellular and molecular processes of atherosclerosis, different mass spectrometry-based omics approaches, and the studies mostly done on clinical samples of atheroma plaque using mass spectrometry-based proteomics, metabolomics and lipidomics approaches.PMID:36426765 | DOI:10.1039/d2mo00260d

Anal Chem. 2022 Nov 25. doi: 10.1021/acs.analchem.2c03986. Online ahead of print.ABSTRACTOne of the technical challenges in the field of metabolomics is the development of a single-run method to detect the full complement of polar metabolites in biological samples. However, an ideal method to meet this demand has not yet been developed. Herein, we proposed a simple methodology that enables the comprehensive and simultaneous analysis of polar metabolites using unified-hydrophilic-interaction/anion-exchange liquid chromatography mass spectrometry (unified-HILIC/AEX/MS) with a polymer-based mixed amines column composed of methacrylate-based polymer particles with primary, secondary, tertiary, and quaternary amines as functional groups. The optimized unified-HILIC/AEX/MS method is composed of two consecutive chromatographic separations, HILIC-dominant separation for cationic, uncharged, and zwitterionic polar metabolites [retention times (RTs) = 0-12.8 min] and AEX-dominant separation for polar anionic metabolites (RTs = 12.8-26.5 min), by varying the ratio of acetonitrile to 40 mM ammonium bicarbonate solution (pH 9.8). A total of 400 polar metabolites were analyzed simultaneously through a combination of highly efficient separation using unified-HILIC/AEX and remarkably sensitive detection using multiple reaction monitoring-based triple quadrupole mass spectrometry (unified-HILIC/AEX/MS/MS). A nontargeted metabolomic approach using unified-HILIC/AEX high-resolution mass spectrometry (unified-HILIC/AEX/HRMS) also provided more comprehensive information on polar metabolites (3242 metabolic features) in HeLa cell extracts than the conventional HILIC/HRMS method (2068 metabolic features). Our established unified-HILIC/AEX/MS/MS and unified-HILIC/AEX/HRMS methods have several advantages over conventional techniques, including polar metabolome coverage, throughput, and accurate quantitative performance, and represent potentially useful tools for in-depth studies on metabolism and biomarker discovery.PMID:36426757 | DOI:10.1021/acs.analchem.2c03986

J Proteome Res. 2022 Nov 25. doi: 10.1021/acs.jproteome.2c00473. Online ahead of print.ABSTRACTBiomarkers are of central importance for assessing the health state and to guide medical interventions and their efficacy; still, they are lacking for most diseases. Mass spectrometry (MS)-based proteomics is a powerful technology for biomarker discovery but requires sophisticated bioinformatics to identify robust patterns. Machine learning (ML) has become a promising tool for this purpose. However, it is sometimes applied in an opaque manner and generally requires specialized knowledge. To enable easy access to ML for biomarker discovery without any programming or bioinformatics skills, we developed "OmicLearn" (http://OmicLearn.org), an open-source browser-based ML tool using the latest advances in the Python ML ecosystem. Data matrices from omics experiments are easily uploaded to an online or a locally installed web server. OmicLearn enables rapid exploration of the suitability of various ML algorithms for the experimental data sets. It fosters open science via transparent assessment of state-of-the-art algorithms in a standardized format for proteomics and other omics sciences.PMID:36426751 | DOI:10.1021/acs.jproteome.2c00473

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