PubMed

Food Res Int. 2023 Aug;170:112934. doi: 10.1016/j.foodres.2023.112934. Epub 2023 May 3.ABSTRACTDuring storage, Aspergillus carbonarius (A. carbonarius) can easily infect grape berries, resulting in a pronounced decline in nutritional value and substantial economic loss for the grape industry. Characterised by broad-spectrum antibacterial activity, eugenol is proven to significantly inhibit A. carbonarius and ochratoxin A (OTA) in vitro. In this study, the potential mechanism of eugenol against A. carbonarius in grapes ('Kyoho') was evaluated using integrative transcriptomic and metabolomics analyses. After eugenol treatment at 50 mM, the inhibition of OTA was reduced by 100%, despite a 56.2% inhibition of A. carbonarius. In the meantime, mycelial growth was completely inhibited by 100 mM eugenol in grape berries. The application of eugenol to grapes stimulated the activity of several enzymes involved in disease resistance, namely catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), chitinase (CHI), β-1,3-glucanase (GLU), cinnamate-4-hydroxylase (C4H), phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL) and glutathione (GSH) content. In addition, the contents of abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) in eugenol-treated grapes were higher after A. carbonarius inoculation. Combined transcriptomic and metabolomic analysis revealed that in phenylpropane biosynthesis, there were a variety of differentially expressed metabolites (DEMs) and differentially expressed genes (DEGs), and the plant hormone signalling pathway changed significantly. Among these, the levels of 47 polyphenol metabolites significantly increased in eugenol-treated grape berries compared to noneugenol-treated berries. Meanwhile, we investigated the transcript levels of 39 genes in 6 phytohormones signalling in response to eugenol-treated grape berries followed by A. carbonarius inoculation. These results suggest that eugenol positively improved the disease resistance of grapes and might be potentially beneficial for the prevention and treatment of A. carbonarius-caused disease.PMID:37316002 | DOI:10.1016/j.foodres.2023.112934

Metabolism. 2023 Jun 12:155628. doi: 10.1016/j.metabol.2023.155628. Online ahead of print.ABSTRACTBACKGROUND: The Metabolic reprogramming of tumor cells plays a vital role in the progression of hepatocellular carcinoma. Organic cation/carnitine transporter 2 (OCTN2), a sodium-ion dependent carnitine transporter and a sodium-ion independent tetraethylammonium (TEA) transporter, has been reported to contribute tumor malignancies and metabolic dysregulation in renal and esophageal carcinoma. However, the role of lipid metabolism deregulation mediated by OCTN2 in HCC cells has not been clarified.METHODS: Bioinformatics analyses and immunohistochemistry assay were employed to identify OCTN2 expression in HCC tissues. The correlation between OCTN2 expression and prognosis was elucidated through K-M survival analysis. The expression and function of OCTN2 were examined via the assays of western blotting, sphere formation, cell proliferation, migration and invasion. The mechanism of OCTN2-mediated HCC malignancies was investigated through RNA-seq and metabolomic analyses. Furthermore, xenograft tumor models based on HCC cells with different OCTN2 expression levels were conducted to analyze the tumorigenic and targetable role of OCTN2 in vivo.RESULTS: We found that gradually focused OCTN2 was significantly upregulated in HCC and tightly associated with poor prognosis. Additionally, OCTN2 upregulation promoted HCC cells proliferation and migration in vitro and augmented the growth and metastasis of HCC. Moreover, OCTN2 promoted the cancer stem-like properties of HCC by increasing fatty acid oxidation and oxidative phosphorylation. Mechanistically, PGC-1α signaling participated in the HCC cancer stem-like properties mediated by OCTN2 overexpression, which is confirmed by in vitro and in vivo analyses. Furthermore, OCTN2 upregulation may be transcriptionally activated by YY1 in HCC. Particularly, treatment with mildronate, an inhibitor of OCTN2, showed a therapeutic influence on HCC in vitro and in vivo.CONCLUSIONS: Our findings demonstrate that OCTN2 plays a critical metabolic role in HCC cancer stemness maintenance and HCC progression, providing evidence for OCTN2 as a promising target for HCC therapy.PMID:37315888 | DOI:10.1016/j.metabol.2023.155628

Pharmacol Res. 2023 Jun 12:106817. doi: 10.1016/j.phrs.2023.106817. Online ahead of print.ABSTRACTA potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC50 values of 4.14 ± 0.35μM, 26.53 ± 3.12μM and 11.62 ± 1.44μM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.PMID:37315824 | DOI:10.1016/j.phrs.2023.106817

J Biol Chem. 2023 Jun 12:104919. doi: 10.1016/j.jbc.2023.104919. Online ahead of print.ABSTRACTCoenzymes are important for all classes of enzymatic reactions and essential for cellular metabolism. Most coenzymes are synthesized from dedicated precursors, also referred to as vitamins, which prototrophic bacteria can either produce themselves from simpler substrates or take up from the environment. The extent to which prototrophs use supplied vitamins and whether externally available vitamins affect the size of intracellular coenzyme pools and control endogenous vitamin synthesis is currently largely unknown. Here, we studied coenzyme pool sizes and vitamin incorporation into coenzymes during growth on different carbon source and vitamin supplementation regimes using metabolomics approaches. We found that the model bacterium Escherichia coli incorporated pyridoxal, niacin, and pantothenate into pyridoxal 5'-phosphate, NAD, and coenzyme A (CoA), respectively. In contrast, riboflavin was not taken up and was produced exclusively endogenously. Coenzyme pools were mostly homeostatic and not affected by externally supplied precursors. Remarkably, we found that pantothenate is not incorporated into CoA as such but is first degraded to pantoate and β-alanine and then rebuilt. This pattern was conserved in various bacterial isolates, suggesting a preference for β-alanine over pantothenate utilization in CoA synthesis. Finally, we found that the endogenous synthesis of coenzyme precursors remains active when vitamins are supplied, which is consistent with described expression data of genes for enzymes involved in coenzyme biosynthesis under these conditions. Continued production of endogenous coenzymes may ensure rapid synthesis of the mature coenzyme under changing environmental conditions, protect against coenzyme limitation, and explain vitamin availability in naturally oligotrophic environments.PMID:37315792 | DOI:10.1016/j.jbc.2023.104919

Clin Chim Acta. 2023 Jun 12:117445. doi: 10.1016/j.cca.2023.117445. Online ahead of print.ABSTRACTOver the last decade, increasing research has focused on urinary exosomes (UEs) in biological fluids and their relationship with physiological and pathological processes. UEs are membranous vesicles with a size of 40-100 nm, containing a number of bioactive molecules such as proteins, lipids, mRNAs, and miRNAs. These vesicles are an inexpensive non-invasive source that can be used in clinical settings to differentiate healthy patients from diseased patients, thereby serving as potential biomarkers for the early identification of disease. Recent studies have reported the isolation of small molecules called exosomal metabolites from individuals' urine with different diseases. These metabolites could utilize for a variety of purposes, such as the discovery of biomarkers, investigation of mechanisms related to disease development, and importantly prediction of cardiovascular diseases (CVDs) risk factors, including thrombosis, inflammation, oxidative stress, hyperlipidemia as well as homocysteine. It has been indicated that alteration in urinary metabolites of N1-methylnicotinamide, 4-aminohippuric acid, and citric acid can be valuable in predicting cardiovascular risk factors, providing a novel approach to evaluating the pathological status of CVDs. Since the UEs metabolome has been clearly and precisely so far unexplored in CVDs, the present study has specifically addressed the role of the mentioned metabolites in the prediction of CVDs risk factors.PMID:37315726 | DOI:10.1016/j.cca.2023.117445

Transl Res. 2023 Jun 12:S1931-5244(23)00103-2. doi: 10.1016/j.trsl.2023.06.001. Online ahead of print.ABSTRACTChronic heart failure (CHF) as a long-term disease is highly prevalent in elder people worldwide. Early diagnosis and treatments are crucial for preventing the development of CHF. Herein, we aimed to identify novel diagnostic biomarker, therapeutic target and drug for CHF. Untargeted metabolomic analysis has been used to characterize the different metabolomic profile between CHF patients and healthy people. Meanwhile, the targeted metabolomic study demonstrated the elevation of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) in the serum of CHF patients and coronary artery ligation-induced CHF mice. Subsequently, we firstly observed that elevation of CMPF impaired cardiac function and aggravated myocardial injury by enhancing fatty acid oxidation (FAO). Interestingly, inhibition of responsible transporters organic anion transporter 1/3 (OAT1/3) has been found to decrease the CMPF level, and suppress FAO-related key protein expressions including peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferative activated receptor-α (PGC1-α), carnitine palmitoyl transferase 1 (CPT1), and malonyl CoA decarboxylase (MCD) in coronary artery ligation-induced CHF mice. Meanwhile, the inhibitor of OAT1/3 presented an excellent improvement in cardiac function and histological injury. Based on the above findings, molecular docking was adopted to screen the potential therapeutic drug targeting OAT1/3, and ruscogenin (RUS) exhibited a great binding affinity with OAT1 and OAT3. Next, it was verified that RUS could remarkedly decrease the expression of OAT1/3 and CMPF levels in heart tissue of CHF mice, as well as suppress the expression of FAO-related proteins. What's more, RUS can effectively improve cardiac function, myocardial fibrosis and morphological damage. Collectively, this study provided a potential metabolic marker CMPF and novel target OAT1/3 for CHF, which were demonstrated to be involved in FAO. And RUS was identified as a potential anti-FAO drug for CHF by regulating OAT1/3. Background Chronic heart failure (CHF) as a long-term disease is highly prevalent in elder people worldwide. Early diagnosis and treatments are crucial for preventing the development of CHF. Hence, there is an urgent need to identify novel biomarkers and therapeutic targets.PMID:37315712 | DOI:10.1016/j.trsl.2023.06.001

J Ethnopharmacol. 2023 Jun 12:116695. doi: 10.1016/j.jep.2023.116695. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The present study aims to evaluate the efficacy of Venenum Bufonis (VBF), a traditional Chinese medicine derived from the dried secretions of the Chinese toad, in treating colorectal cancer (CRC). The comprehensive roles of VBF in CRC through systems biology and metabolomics approaches have been rarely investigated.AIMS OF THE STUDY: The study sought to uncover the potential underlying mechanisms of VBF's anti-cancer effects by investigating the impact of VBF on cellular metabolic balance.MATERIALS AND METHODS: An integrative approach combining biological network analysis, molecular docking and multi-dose metabolomics was used to predict the effects and mechanisms of VBF in CRC treatment. The prediction was verified by cell viability assay, EdU assay and flow cytometry.RESULTS: The results of the study indicate that VBF presents anti-CRC effects and impacts cellular metabolic balance through its impact on cell cycle-regulating proteins, such as MTOR, CDK1, and TOP2A. The results of the multi-dose metabolomics analysis suggest a dose-dependent reduction of metabolites related to DNA synthesis after VBF treatment, while the EdU and flow cytometry results indicate that VBF inhibits cell proliferation and arrests the cell cycle at the S and G2/M phases.CONCLUSIONS: These findings suggest that VBF disrupts purine and pyrimidine pathways in CRC cancer cells, leading to cell cycle arrest. This proposed workflow integrating molecular docking, multi-dose metabolomics, and biological validation, which contented EdU assay, cell cycle assay, provides a valuable framework for future similar studies.PMID:37315651 | DOI:10.1016/j.jep.2023.116695

Sci Total Environ. 2023 Jun 12:164761. doi: 10.1016/j.scitotenv.2023.164761. Online ahead of print.ABSTRACTEnvironmental arsenic (As) exposure has been associated with gestational diabetes mellitus (GDM) risk. Our recent study found that GDM was positively associated with urinary As3+ level while negatively correlated to As5+. However, the mechanisms underlying the association between arsenic species and GDM remain largely unknown. In the present study, through the measurement of urinary arsenic species and metabolome analysis in 399 pregnant women, we aimed to identify the metabolic biomarkers that may link arsenic exposure to GDM based on a novel systems epidemiology strategy termed meet-in-metabolite-analysis (MIMA). The metabolomics analysis revealed that 20 and 16 urinary metabolites were relevant to arsenic exposure and GDM, respectively. Among them, 12 metabolites were identified to be both arsenic- and GDM-related, which are mainly involved in purine metabolism, one‑carbon metabolism (OCM) and glycometabolism. Moreover, it was further showed that the regulation of thiosulfate (AOR: 2.52; 95 % CI: 1.33, 4.77) and phosphoroselenoic acid (AOR: 2.35; 95 % CI: 1.31, 4.22) could significantly contribute to the negative association between As5+ and GDM. Considering the biological functions of these metabolites, it is suggested that As5+ may reduce GDM risk by disturbing OCM in the pregnant women. These data will provide novel insights into the mechanism of action of environmental arsenic exposure on GDM incidence from the aspect of metabolism disorder.PMID:37315596 | DOI:10.1016/j.scitotenv.2023.164761

Ecotoxicol Environ Saf. 2023 Jun 12;262:115128. doi: 10.1016/j.ecoenv.2023.115128. Online ahead of print.ABSTRACTRare earth elements (REEs) have been widely used in traditional and high-tech fields, and high doses of REEs are considered a risk to the ecosystem. Although the influence of arbuscular mycorrhizal fungi (AMF) in promoting host resistance to heavy metal (HM) stress has been well documented, the molecular mechanism by which AMF symbiosis enhances plant tolerance to REEs is still unclear. A pot experiment was conducted to investigate the molecular mechanism by which the AMF Claroideoglomus etunicatum promotes maize (Zea mays) seedling tolerance to lanthanum (La) stress (100 mg·kg-1 La). C. etunicatum symbiosis significantly improved maize seedling growth, P and La uptake and photosynthesis. Transcriptome, proteome, and metabolome analyses performed alone and together revealed that differentially expressed genes (DEGs) related to auxin /indole-3-acetic acid (AUX/IAA) and the DEGs and differentially expressed proteins (DEPs) related to ATP-binding cassette (ABC) transporters, natural resistance-associated macrophage proteins (Nramp6), vacuoles and vesicles were upregulated. In contrast, photosynthesis-related DEGs and DEPs were downregulated, and 1-phosphatidyl-1D-myo-inositol 3-phosphate (PI(3)P) was more abundant under C. etunicatum symbiosis. C. etunicatum symbiosis can promote plant growth by increasing P uptake, regulating plant hormone signal transduction, photosynthesis and glycerophospholipid metabolism pathways and enhancing La transport and compartmentalization in vacuoles and vesicles. The results provide new insights into the promotion of plant REE tolerance by AMF symbiosis and the possibility of utilizing AMF-maize interactions in REE phytoremediation and recycling.PMID:37315361 | DOI:10.1016/j.ecoenv.2023.115128

Sci Adv. 2023 Jun 16;9(24):eadh4299. doi: 10.1126/sciadv.adh4299. Epub 2023 Jun 14.ABSTRACTNature has evolved eight different pathways for the capture and conversion of CO2, including the Calvin-Benson-Bassham cycle of photosynthesis. Yet, these pathways underlie constrains and only represent a fraction of the thousands of theoretically possible solutions. To overcome the limitations of natural evolution, we introduce the HydrOxyPropionyl-CoA/Acrylyl-CoA (HOPAC) cycle, a new-to-nature CO2-fixation pathway that was designed through metabolic retrosynthesis around the reductive carboxylation of acrylyl-CoA, a highly efficient principle of CO2 fixation. We realized the HOPAC cycle in a step-wise fashion and used rational engineering approaches and machine learning-guided workflows to further optimize its output by more than one order of magnitude. Version 4.0 of the HOPAC cycle encompasses 11 enzymes from six different organisms, converting ~3.0 mM CO2 into glycolate within 2 hours. Our work moves the hypothetical HOPAC cycle from a theoretical design into an established in vitro system that forms the basis for different potential applications.PMID:37315145 | DOI:10.1126/sciadv.adh4299

Anal Chem. 2023 Jun 14. doi: 10.1021/acs.analchem.3c00764. Online ahead of print.ABSTRACTPeak-detection algorithms currently used to process untargeted metabolomics data were designed to maximize sensitivity at the sacrifice of selectively. Peak lists returned by conventional software tools therefore contain a high density of artifacts that do not represent real chemical analytes, which, in turn, hinder downstream analyses. Although some innovative approaches to remove artifacts have recently been introduced, they involve extensive user intervention due to the diversity of peak shapes present within and across metabolomics data sets. To address this bottleneck in metabolomics data processing, we developed a semisupervised deep learning-based approach, PeakDetective, for classification of detected peaks as artifacts or true peaks. Our approach utilizes two techniques for artifact removal. First, an unsupervised autoencoder is used to extract a low-dimensional, latent representation of each peak. Second, a classifier is trained with active learning to discriminate between artifacts and true peaks. Through active learning, the classifier is trained with less than 100 user-labeled peaks in a matter of minutes. Given the speed of its training, PeakDetective can be rapidly tailored to specific LC/MS methods and sample types to maximize performance on each type of data set. In addition to curation, the trained models can also be utilized for peak detection to immediately detect peaks with both high sensitivity and selectivity. We validated PeakDetective on five diverse LC/MS data sets, where PeakDetective showed greater accuracy compared to current approaches. When applied to a SARS-CoV-2 data set, PeakDetective enabled more statistically significant metabolites to be detected. PeakDetective is open source and available as a Python package at https://github.com/pattilab/PeakDetective.PMID:37314824 | DOI:10.1021/acs.analchem.3c00764

Probiotics Antimicrob Proteins. 2023 Jun 14. doi: 10.1007/s12602-023-10101-6. Online ahead of print.ABSTRACTProbiotics are used to prevent antibiotic-associated diarrhea (AAD) via the restoration of the gut microbiota. However, the precise effects of Akkermansia muciniphila (Akk), which is a promising probiotics, on AAD are unknown. Here, AAD models were established via the administration of lincomycin and ampicillin with or without pasteurized Akk or Amuc_1100 treatment. A diffusion test revealed that Akk was susceptible to the majority of the antibiotics, such as ampicillin. These effects were confirmed by the reduced Akk abundance in AAD model mice. Pasteurized Akk or Amuc_1100 significantly decreased the diarrhea status score and colon injury of AAD model mice. Additionally, these treatments significantly decreased the relative abundance of Citrobacter at genus level and reshaped the metabolic function of gut microbiota. Notably, pasteurized Akk or Amuc_1100 significantly changed the serum metabolome of AAD model mice. In addition, pasteurized Akk or Amuc_1100 suppressed intestinal inflammation by upregulating the expression of GPR109A and SLC5A8 and downregulating the expression of TNFα, IFNγ, IL1β, and IL6. Furthermore, they enhanced water and electrolyte absorption by upregulating AQP4, SLC26A3, and NHE3. Pasteurized Akk or Amuc_1100 also restored intestinal barrier function by ameliorating the downregulation of ZO-1, OCLN, CLDN4, and Muc2 in AAD model mice. In summary, optimizing intestinal health with pasteurized Akk or Amuc_1100 may serve as an approach for preventing AAD.PMID:37314693 | DOI:10.1007/s12602-023-10101-6

Anal Chem. 2023 Jun 14. doi: 10.1021/acs.analchem.3c01072. Online ahead of print.ABSTRACTUntargeted mass spectrometry is a robust tool for biology, but it usually requires a large amount of time on data analysis, especially for system biology. A framework called Multiple-Chemical nebula (MCnebula) was developed herein to facilitate the LC-MS data analysis process by focusing on critical chemical classes and visualization in multiple dimensions. This framework consists of three vital steps as follows: (1) abundance-based classes (ABC) selection algorithm, (2) critical chemical classes to classify "features" (corresponding to compounds), and (3) visualization as multiple Child-Nebulae (network graph) with annotation, chemical classification, and structure. Notably, MCnebula can be used to explore the classification and structural characteristic of unknown compounds beyond the limit of the spectral library. Moreover, it is intuitive and convenient for pathway analysis and biomarker discovery because of its function of ABC selection and visualization. MCnebula was implemented in the R language. A series of tools in R packages were provided to facilitate downstream analysis in an MCnebula-featured way, including feature selection, homology tracing of top features, pathway enrichment analysis, heat map clustering analysis, spectral visualization analysis, chemical information query, and output analysis reports. The broad utility of MCnebula was illustrated by a human-derived serum data set for metabolomics analysis. The results indicated that "Acyl carnitines" were screened out by tracing structural classes of biomarkers, which was consistent with the reference. A plant-derived data set was investigated to achieve a rapid annotation and discovery of compounds in E. ulmoides.PMID:37314081 | DOI:10.1021/acs.analchem.3c01072

Am J Sports Med. 2023 Jun 14:3635465231177890. doi: 10.1177/03635465231177890. Online ahead of print.ABSTRACTBACKGROUND: An Achilles tendon rupture (ATR) is a frequent injury and results in the activation of tendon cells and collagen expression, but it is unknown to what extent turnover of the tendon matrix is altered before or after a rupture.PURPOSE/HYPOTHESIS: The purpose of this study was to characterize tendon tissue turnover before and immediately after an acute rupture in patients. It was hypothesized that a rupture would result in pronounced collagen synthesis in the early phase (first 2 weeks) after the injury.STUDY DESIGN: Cross-sectional study; Level of evidence, 3.METHODS: The study included patients (N = 18) eligible for surgery after an ATR. At the time of inclusion, the patients ingested deuterium oxide (2H2O) orally, and on the day of surgery (within 14 days of the injury), they received a 3-hour flood-primed infusion of an 15N-proline tracer. During surgery, the patients had 1 biopsy specimen taken from the ruptured part of the Achilles tendon and 1 that was 3 to 5 cm proximal to the rupture as a control. The biopsy specimens were analyzed for carbon-14 (14C) levels in the tissue to calculate long-term turnover (years), incorporation of 2H-alanine (from 2H2O) into the tissue to calculate the fractional synthesis rate (FSR) of proteins in the short term (days), and incorporation of 15N-proline into the tissue to calculate the acute FSR (hours).RESULTS: Both the rupture and the control samples showed consistently lower levels of 14C compared with the predicted level of 14C in a healthy tendon, which indicated increased tendon turnover in a fraction (48% newly synthesized) of the Achilles tendon already for a prolonged period before the rupture. Over the first days after the rupture, the synthesis rate for collagen was relatively constant, and the average synthesis rate on the day of surgery (2-14 days after the rupture) was 0.025% per hour, irrespective of the length of time after a rupture and the site of sampling (rupture vs control). No differences were found in the FSR between the rupture and control samples in the days after the rupture.CONCLUSION: Higher than normal tissue turnover in the Achilles tendon before a rupture indicated that changes in the tendon tissue preceded the injury. In addition, we observed no increase in tendon collagen tissue turnover in the first 2 weeks after an ATR. This favors the view that an increase in the formation of new tendon collagen is not an immediate phenomenon during the regeneration of ruptured tendons in patients.REGISTRATION: NCT03931486 (ClinicalTrials.gov identifier).PMID:37313851 | DOI:10.1177/03635465231177890

Ann Neurosci. 2023 Jan;30(1):11-19. doi: 10.1177/09727531221117634. Epub 2022 Aug 27.ABSTRACTBACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder that mainly affects the aged population. Transcranial magnetic field (MF) stimulation has shown to provide temporary motor recovery in neurological disorders.PURPOSE: The aim of this study was to understand the cellular and molecular mechanism of low-intensity MF stimulation (17.96 µT; 50Hz; 2 h/day, four weeks) in a rat model of severe PD.METHODS: A clinically relevant, bilateral striatal 6-hydroxydopamine (6-OHDA) lesioned rat model of severe PD was employed to test the efficacy of low-intensity MF stimulation in the management of motor symptoms. The mechanism of action of MF was dissected by assessing the microglial activation, tissue ultrastructure, and cerebrospinal fluid (CSF) metabolomics using microdialysis.RESULTS: We observed a significant improvement in the postural balance and gait after MF exposure with a significant reduction in the number of activated microglia. There was an improvement in striatal dopaminergic innervation and glutamate levels but it did not reach a level of statistical significance.CONCLUSION: MF stimulation helped ameliorate the motor deficits and reduced inflammation but was unable to provide a significant change in terms of dopaminergic innervation and metabolic profile in the severe 6-OHDA PD rat model.PMID:37313335 | PMC:PMC10259148 | DOI:10.1177/09727531221117634

Mol Breed. 2023 Mar 2;43(3):16. doi: 10.1007/s11032-023-01361-9. eCollection 2023 Mar.ABSTRACTBreeding crop varieties with high yield and ideal plant architecture is a desirable goal of agricultural science. The success of "Green Revolution" in cereal crops provides opportunities to incorporate phytohormones in crop breeding. Auxin is a critical phytohormone to determine nearly all the aspects of plant development. Despite the current knowledge regarding auxin biosynthesis, auxin transport and auxin signaling have been well characterized in model Arabidopsis (Arabidopsis thaliana) plants, how auxin regulates crop architecture is far from being understood, and the introduction of auxin biology in crop breeding stays in the theoretical stage. Here, we give an overview on molecular mechanisms of auxin biology in Arabidopsis, and mainly summarize auxin contributions for crop plant development. Furthermore, we propose potential opportunities to integrate auxin biology in soybean (Glycine max) breeding.PMID:37313296 | PMC:PMC10248601 | DOI:10.1007/s11032-023-01361-9

Front Plant Sci. 2023 May 29;14:1208218. doi: 10.3389/fpls.2023.1208218. eCollection 2023.NO ABSTRACTPMID:37313256 | PMC:PMC10258335 | DOI:10.3389/fpls.2023.1208218

Heliyon. 2023 May 27;9(6):e16774. doi: 10.1016/j.heliyon.2023.e16774. eCollection 2023 Jun.ABSTRACTPomegranate (Punica granatum L.) fruits are a historical agricultural product of the Mediterranean basin that became increasingly popular in the latest years for being rich in antioxidants and other micronutrients, and are extensively commercialized as fruits, juice, jams and, in some Eastern countries, as a fermented alcoholic beverage. In this work, four different pomegranate wines specifically designed using combinations of two cultivars (Jolly Red and Smith) and two yeast starters with markedly different characteristics (Saccharomyces cerevisiae Clos and Saccharomyces cerevisiae ex-bayanus EC1118) were analyzed. The chemical characterization of the wines together with the originating unfermented juices was performed by 1H NMR spectroscopy metabolomic analysis. The full spectra were used for unsupervised and supervised statistical multivariate analysis (MVA), namely Principal Component Analysis (PCA), Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), and sparse PCA (SPCA). The MVA of the wines showed a clear discrimination between the cultivars, and a smaller, yet significant, discrimination between the yeasts used. In particular, a higher content of citrate and gallate was observed for the Smith cv. and, on the contrary, a statistically significant higher content of fructose, malate, glycerol, 2,3 butanediol, trigonelline, aromatic amino acids and 4-hydrophenylacetate was observed in Jolly Red pomegranate wines samples. Significant interaction among the pomegranate cultivar and the fermenting yeast was also observed. Sensorial analysis was performed by a panel of testing experts. MVA of tasting data showed that the cultivar significantly affected the organoleptic parameters considered, while the yeast had a minor impact. Correlation analysis between NMR-detected metabolites and organoleptic descriptors identified several potential sensorially-active molecules as those significantly impacting the characteristics of the pomegranate wines.PMID:37313136 | PMC:PMC10258421 | DOI:10.1016/j.heliyon.2023.e16774

Digit Health. 2023 May 31;9:20552076231179007. doi: 10.1177/20552076231179007. eCollection 2023 Jan-Dec.ABSTRACTBACKGROUND: Diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to the lack of specific symptoms and screening methods. Only less than 10% of PDAC patients are candidates for surgery at the time of diagnosis. Thus, there is a great global unmet need for valuable biomarkers that could improve the opportunity to detect PDAC at the resectable stage. This study aimed to develop a potential biomarker model for the detection of resectable PDAC by tissue and serum metabolomics.METHODS: Ultra-high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) was performed for metabolome quantification in 98 serum samples (49 PDAC patients and 49 healthy controls (HCs)) and 20 pairs of matched pancreatic cancer tissues (PCTs) and adjacent noncancerous tissues (ANTs) from PDAC patients. Univariate and multivariate analyses were used to profile the differential metabolites between PDAC and HC.RESULTS: A total of 12 differential metabolites were present in both serum and tissue samples of PDAC. Among them, a total of eight differential metabolites showed the same expressional levels, including four upregulated and four downregulated metabolites. Finally, a panel of three metabolites including 16-hydroxypalmitic acid, phenylalanine, and norleucine was constructed by logistic regression analysis. Notably, the panel was capable of distinguishing resectable PDAC from HC with an AUC value of 0.942. Additionally, a multimarker model based on the 3-metabolites-based panel and CA19-9 showed a better performance than the metabolites panel or CA19-9 alone (AUC: 0.968 vs. 0.942, 0.850).CONCLUSIONS: Taken together, the resectable early-stage PDAC has unique metabolic features in serum and tissue samples. The defined panel of three metabolites has the potential value for early screening of PDAC at the resectable stage.PMID:37312938 | PMC:PMC10259126 | DOI:10.1177/20552076231179007

Mol Breed. 2023 Apr 21;43(5):33. doi: 10.1007/s11032-023-01380-6. eCollection 2023 May.ABSTRACTSoybean is one of the most versatile crops for oil production, human diets, and feedstocks. The vegetative biomass of soybean is an important determinant of seed yield and is crucial for the forage usages. However, the genetic control of soybean biomass is not well explained. In this work, we used a soybean germplasm population, including 231 improved cultivars, 207 landraces, and 121 wild soybeans, to investigate the genetic basis of biomass accumulation of soybean plants at the V6 stage. We found that biomass-related traits, including NDW (nodule dry weight), RDW (root dry weight), SDW (shoot dry weight), and TDW (total dry weight), were domesticated during soybean evolution. In total, 10 loci, encompassing 47 putative candidate genes, were detected for all biomass-related traits by a genome-wide association study. Among these loci, seven domestication sweeps and six improvement sweeps were identified. Glyma.05G047900, a purple acid phosphatase, was a strong candidate gene to improve biomass for future soybean breeding. This study provided new insights into the genetic basis of biomass accumulation during soybean evolution.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11032-023-01380-6.PMID:37312748 | PMC:PMC10248709 | DOI:10.1007/s11032-023-01380-6