PubMed

Front Microbiol. 2023 Feb 2;14:1117644. doi: 10.3389/fmicb.2023.1117644. eCollection 2023.ABSTRACTBACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. Dysbiosis of gut microbiome has been identified as one of the key environmental factors contributing to NAFLD. As an essential nutrition, Vitamin D (VD) plays an important role in regulating gut microbiota based on its receptor (Vitamin D Receptor, VDR) which is highly expressed in the gastrointestinal tract.METHODS: Rats were fed with HFD (high-fat diet) for 12 weeks. And the rats were treated with VD two times a week by intraperitoneal injection for 12 weeks. H&E staining combined with plasma biochemical index was performed to characterize pathological changes and function of the liver. Fecal microbiota 16S rRNA gene sequencing and metabolomics were taken to reveal the altered gut microbiota and metabolites.RESULT: The VD alleviates the HFD-induced lipid accumulation in the liver as well as decreases the levels of amlodipine besylate (ALT) and amlodipine aspartate (AST). VD supplement decreased the ratio of phylum Firmicutes/Bacteroidetes (F/B) but increased alpha diversity. In addition, the VD treatment improved the HFD-induced gut microbiota by increasing the Prevotella and Porphyromonadaceae and decreasing Mucispirillum, Acetatifactor, Desulfovibrio, and Oscillospira abundance. Furthermore, the capability of tyrosine metabolism, tryptophan metabolism, arginine biosynthesis, and sphingolipid metabolism was enhanced after VD treatment. Consistently, Prevotella positively correlated with tryptophan metabolism and sphingolipid metabolism. Importantly, the Prevotella abundance was positively associated with serotonin, melatonin, tryptamine, L-arginine, and 3-dehydrosphinganine which synthesize from tryptophan, tyrosine, arginosuccinate, and serine, respectively.CONCLUSION: VD treatment inhibited HFD-induced NAFLD accompany by dysbiosis gut microbiota and metabolites, suggesting that VD supplement could be a potential intervention used for NAFLD treatment by targeting the specific microbiota.PMID:36819064 | PMC:PMC9932697 | DOI:10.3389/fmicb.2023.1117644

Front Microbiol. 2023 Feb 1;14:1077106. doi: 10.3389/fmicb.2023.1077106. eCollection 2023.ABSTRACTThe rise and extensive spread of antimicrobial resistance (AMR) has become a growing concern, and a threat to the environment and human health globally. The majority of current AMR identification methods used in clinical setting are based on traditional microbiology culture-dependent techniques which are time-consuming or expensive to be implemented, thus appropriate antibiotic stewardship is provided retrospectively which means the first line of treatment is to hope that a broad-spectrum antibiotic works. Hence, culture-independent and single-cell technologies are needed to allow for rapid detection and identification of antimicrobial-resistant bacteria and to support a more targeted and effective antibiotic therapy preventing further development and spread of AMR. In this study, for the first time, a non-destructive phenotyping method of optical photothermal infrared (O-PTIR) spectroscopy, coupled with deuterium isotope probing (DIP) and multivariate statistical analysis was employed as a metabolic fingerprinting approach to detect AMR in Uropathogenic Escherichia coli (UPEC) at both single-cell and population levels. Principal component-discriminant function analysis (PC-DFA) of FT-IR and O-PTIR spectral data showed clear clustering patterns as a result of distinctive spectral shifts (C-D signature peaks) originating from deuterium incorporation into bacterial cells, allowing for rapid detection and classification of sensitive and resistant isolates at the single-cell level. Furthermore, the single-frequency images obtained using the C-D signature peak at 2,163 cm-1 clearly displayed the reduced ability of the trimethoprim-sensitive strain for incorporating deuterium when exposed to this antibiotic, compared to the untreated condition. Hence, the results of this study indicated that O-PTIR can be employed as an efficient tool for the rapid detection of AMR at the single-cell level.PMID:36819022 | PMC:PMC9929359 | DOI:10.3389/fmicb.2023.1077106

Front Microbiol. 2023 Feb 1;14:1079353. doi: 10.3389/fmicb.2023.1079353. eCollection 2023.ABSTRACTMorels (Morchella) are one of the most popular edible fungi in the world, especially known for their rich nutrition and delicious taste. Earlier research indicates that the production of fruiting bodies can be affected by the growth of mycelium. To investigate the molecular mechanisms underlying mycelium growth in Morchella importuna, we performed transcriptome analysis and metabolomics analysis of three growth stages of the hypha of M. importuna. As a result, 24 differentially expressed genes, such as transketolase (tktA), glucose-6-phosphate dehydrogenase (G6PDH), fructose-diphosphate aldolase (Fba), and ribose-5-phosphate isomerase (rpiA), as well as 15 differentially accumulated metabolites, including succinate and oxaloacetate, were identified and considered as the key genes and metabolites to mycelium growth in M. importuna. In addition, guanosine 3',5'-cyclic monophosphate (cGMP), guanosine-5'-monophosphate (GMP), and several small peptides were found to differentially accumulate in different growth stages. Furthermore, five pathways, namely, starch and sucrose metabolism, pentose and glucuronate interconversions, fructose and mannose metabolism, tyrosine metabolism, and purine nucleotides, enriched by most DEGs, existed in the three compared groups and were also recognized as important pathways for the development of mycelium in morels. The comprehensive transcriptomics and metabolomics data generated in our study provided valuable information for understanding the mycelium growth of M. importuna, and these data also unveiled the key genes, metabolites, and pathways involved in mycelium growth. This research provides a great theoretical basis for the stable production and breeding of morels.PMID:36819010 | PMC:PMC9929000 | DOI:10.3389/fmicb.2023.1079353

Front Plant Sci. 2023 Feb 1;14:1125194. doi: 10.3389/fpls.2023.1125194. eCollection 2023.ABSTRACTPowdery mildew is a fungal disease devastating to wheat, causing significant quality and yield loss. Flavonoids are important secondary plant metabolites that confer resistance to biotic and abiotic stress. However, whether they play a role in powdery mildew resistance in wheat has yet to be explored. In the present study, we combined transcriptome and metabolome analyses to compare differentially expressed genes (DEGs) and differentially accumulated flavonoids identified in plants with and without powdery mildew inoculation. Transcriptome analysis identified 4,329 DEGs in susceptible wheat cv. Jimai229, and 8,493 in resistant cv. HHG46. The DEGs were functionally enriched using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, revealing the flavonoid synthesis pathway as the most significant in both cultivars. This was consistent with the upregulation of flavonoid synthesis pathway genes observed by quantitative PCR. Metabolome analysis indicated flavone and flavonol biosynthesis pathways as the most significantly enriched following powdery mildew inoculation. An accumulation of total flavonoids content was also found to be induced by powdery mildew infection. Exogenous flavonoids treatment of inoculated plants led to less severe infection, with fewer and smaller powdery mildew spots on the wheat leaves. This reduction is speculated to be regulated through malondialdehyde content and the activities of peroxidase and catalase. Our study provides a fundamental theory for further exploration of the potential of flavonoids as biological prevention and control agents against powdery mildew in wheat.PMID:36818890 | PMC:PMC9929363 | DOI:10.3389/fpls.2023.1125194

Front Plant Sci. 2023 Feb 2;14:1106857. doi: 10.3389/fpls.2023.1106857. eCollection 2023.ABSTRACTINTRODUCTION: Drought is the largest abiotic factor impacting agriculture. Plants are challenged by both natural and artificial stressors because they are immobile. To produce drought-resistant plants, we need to know how plants react to drought. A largescale proteome study of leaf and root tissue found drought-responsive proteins. Tomato as a vegetable is grown worldwide. Agricultural biotechnology focuses on creating drought-resistant cultivars. This is important because tomato drought is so widespread. Breeders have worked to improve tomato quality, production, and stress resistance. Conventional breeding approaches have only increased drought tolerance because of drought's complexity. Many studies have examined how tomatoes handle drought. With genomics, transcriptomics, proteomics, metabolomics, and modern sequencing technologies, it's easier to find drought-responsive genes.METHOD: Biotechnology and in silico studies has helped demonstrate the function of drought-sensitive genes and generate drought-resistant plant types. The latest tomato genome editing technology is another. WRKY genes are plant transcription factors. They help plants grow and respond to both natural and artificial stimuli. To make plants that can handle stress, we need to know how WRKY-proteins, which are transcription factors, work with other proteins and ligands in plant cells by molecular docking and modeling study.RESULT: Abscisic acid, a plant hormone generated in stressed roots, was used here to make plants drought-resistant. Abscisic acid binds WRKY with binding affinity -7.4kcal/mol and inhibitory concentration (Ki) 0.12 microM.DISCUSSION: This study aims to modulate the transcription factor so plants can handle drought and stress better. Therefore, polyphenols found to make Solanum lycopersicum more drought-tolerant.PMID:36818888 | PMC:PMC9933497 | DOI:10.3389/fpls.2023.1106857

Front Plant Sci. 2023 Feb 3;14:1117868. doi: 10.3389/fpls.2023.1117868. eCollection 2023.ABSTRACTINTRODUCTION: Salinity critically affects the growth and development of alfalfa (Medicago sativa), making it necessary to understand the molecular mechanism of alfalfa's adaptation to salt stress.METHODS: In this study, alfalfa roots were subjected to salt stress and transcriptomics and metabolomics analyses were performed.RESULTS: The results showed that flavonoid synthesis, hormone synthesis, and transduction pathways may be involved in the alfalfa salt stress adaptation reaction, and that they are related. Combined analysis of differential genes and differential metabolites found that dihydroquercetin and beta-ring hydroxylase (LUT5), ABA responsive element binding factor 2 (ABF2), protein phosphatase PP2C (PP2C) and abscisic acid (ABA) receptor PYL2 (PYL), luteolinidin was significantly correlated with PP2C and phytochrome-interacting factor 4 (PIF4) and (+)-7-isomethyl jasmonate were significantly correlated with flavonol synthase (FLS) gene. (+)-7-isomethyl jasmonate and homoeriodictyol chalcone were significantly correlated with peroxidase (POD). POD was significantly up-regulated under NaCl stress for 6 and 24 h. Moreover, flavonoids, gibberellin (GA), jasmonic acid (JA) and ABA were suggested to play an important role in alfalfa's response to salt stress. Further, GA,ABA, and JA may be involved in the regulation of flavonoids to improve alfalfa's salt tolerance, and JA may be a key signal to promote the synthesis of flavonoids.DISCUSSION: This study revealed the possible molecular mechanism of alfalfa adaptation to salt stress, and identified a number of salt-tolerance candidate genes from the synthesis and signal transduction pathways of flavonoids and plant hormones, providing new insights into the regulatory network of alfalfa response to salt stress.PMID:36818861 | PMC:PMC9936617 | DOI:10.3389/fpls.2023.1117868

Front Mol Neurosci. 2023 Feb 3;16:1089871. doi: 10.3389/fnmol.2023.1089871. eCollection 2023.ABSTRACTINTRODUCTION: Previous studies have suggested that the dysregulation of purine metabolism may be associated with autism spectrum disorder (ASD). Here, we adopted metabolomics and transcriptomics to verify and explore the underlying molecular mechanism of purine metabolism dysfunction in ASD and identify potential biomarkers within the purine metabolism pathway.METHODS: Ultra-high-performance liquid chromatography-mass spectrometry was used to obtain the plasma metabolic profiles of 12 patients with ASD and 12 typically developing (TD) children. RNA sequencing was used to screen differentially expressed genes related to the purine metabolic pathway and purine receptor-coding genes in 24 children with ASD and 21 healthy controls. Finally, serum uric acid levels were compared in 80 patients with ASD and 174 TD children to validate the omics results.RESULTS: A total of 66 identified metabolites showed significant between-group differences. Network analysis showed that purine metabolism was the most strongly enriched. Uric acid was one of the most highlighted nodes within the network. The transcriptomic study revealed significant differential expression of three purine metabolism-related genes (adenosine deaminase, adenylosuccinate lyase, and bifunctional enzyme neoformans 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase) (p < 0.01) and five purinergic receptor genes (P2X7, P2Y2, P2Y6, P2Y8, and P2Y10) (p < 0.05). In the validation sample, there was a significant difference in serum uric acid levels between the two groups (p < 0.001), and the area under the curve for uric acid was 0.812 (sensitivity, 82.5%; specificity, 63.8%).DISCUSSION: Patients with ASD had dysfunctional purine metabolic pathways, and blood uric acid may be a potential biomarker for ASD.PMID:36818658 | PMC:PMC9935591 | DOI:10.3389/fnmol.2023.1089871

Drug Des Devel Ther. 2023 Feb 11;17:439-457. doi: 10.2147/DDDT.S388932. eCollection 2023.ABSTRACTPURPOSE: Rubia cordifolia L. (RC) is a classic herbal medicine for the treatment of rheumatoid arthritis (RA) and has been used since ancient times. The ethanol extract of Rubia cordifolia L. (RCE) showed obvious anti-RA effects in our previous study. However, further potential mechanisms require more exploration. We aimed to investigate the mechanism of RCE for the treatment of RA by integrating metabolomics and network pharmacology in this study.METHODS: An adjuvant-induced arthritis (AIA) rat model was established, and we evaluated the therapeutic effects of RCE. Metabolomics of serum and urine was used to identify the differential metabolites. Network pharmacology was applied to determine the key metabolites and potential targets. Finally, the potential targets and compounds of RCE were verified by molecular docking.RESULTS: The results indicated that RCE suppressed foot swelling and alleviated joint damage and also had anti-inflammatory properties by inhibiting the expressions of tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, prostaglandin E2 (PGE2), and P65. Ten and seven differential metabolites were found in the serum and urine, respectively, of rats. Six key targets, ie, phospholipase A2 group IIA (PLA2G2A), phospholipase A2 group X (PLA2G10), cytidine deaminase (CDA), uridine-cytidine kinase 2 (UCK2), charcot-leyden crystal galectin (CLC), and 5',3'-nucleotidase, mitochondrial (NT5M), were discovered by network pharmacology and metabolite analysis and were found to be related to glycerophospholipid metabolism and pyrimidine metabolism. Molecular docking confirmed that the favorable compounds showed affinities with the key targets, including alizarin, 6-hydroxyrubiadin, ruberythric acid, and munjistin.CONCLUSION: This study revealed the underlying mechanisms of RCE and provided evidence that will allow researchers to further investigate the functions and components of RCE against RA.PMID:36818604 | PMC:PMC9930591 | DOI:10.2147/DDDT.S388932

Front Immunol. 2023 Feb 2;13:1111723. doi: 10.3389/fimmu.2022.1111723. eCollection 2022.ABSTRACTBACKGROUND: Infants with bronchiolitis are at high risk for developing childhood asthma. While genome-wide association studies suggest common genetic susceptibilities between these conditions, the mechanisms underlying the link remain unclear.OBJECTIVE: Through integrated genetics-metabolomics analysis in this high-risk population, we sought to identify genetically driven metabolites associated with asthma development and genetic loci associated with both these metabolites and asthma susceptibility.METHODS: In a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we profiled the nasopharyngeal metabolome and genotyped the whole genome at hospitalization. We identified asthma-related metabolites from 283 measured compounds and conducted metabolite quantitative trait loci (mtQTL) analyses. We further examined the mtQTL associations by testing shared genetic loci for metabolites and asthma using colocalization analysis and the concordance between the loci and known asthma-susceptibility genes.RESULTS: In 744 infants hospitalized with bronchiolitis, 28 metabolites (e.g., docosapentaenoate [DPA], 1,2-dioleoyl-sn-glycero-3-phosphoglycerol, sphingomyelin) were associated with asthma risk. A total of 349 loci were associated with these metabolites-161 for non-Hispanic white, 120 for non-Hispanic black, and 68 for Hispanics. Of these, there was evidence for 30 shared loci between 16 metabolites and asthma risk (colocalization posterior probability ≥0.5). The significant SNPs within loci were aligned with known asthma-susceptibility genes (e.g., ADORA1, MUC16).CONCLUSION: The integrated genetics-metabolomics analysis identified genetically driven metabolites during infancy that are associated with asthma development and genetic loci associated with both these metabolites and asthma susceptibility. Identifying these metabolites and genetic loci should advance research into the functional mechanisms of the infant bronchiolitis-childhood asthma link.PMID:36818476 | PMC:PMC9936313 | DOI:10.3389/fimmu.2022.1111723

iScience. 2022 Dec 29;26(2):105903. doi: 10.1016/j.isci.2022.105903. eCollection 2023 Feb 17.ABSTRACTPotatoes consist of flavonoids that provide health benefits for human consumers. To learn more about how potato tuber flavonoid accumulation and flesh pigmentation are controlled, we analyzed the transcriptomic and metabolomic profile of potato tubers from three colored potato clones at three developmental phases using an integrated approach. From the 72 flavonoids identified in pigmented flesh, differential abundance was noted for anthocyanins, flavonols, and flavones. Weighted gene co-expression network analysis further allowed modules and candidate genes that positively or negatively regulate flavonoid biosynthesis to be identified. Furthermore, an R2R3-MYB repressor StMYB3 and an R3-MYB repressor StMYBATV involved in the modulation of anthocyanin biosynthesis during tuber development were identified. Both StMYB3 and StMYBATV could interact with the cofactor StbHLH1 and repress anthocyanin biosynthesis. Our results indicate a feedback regulatory mechanism of a coordinated MYB activator-repressor network on fine-tuning of potato tuber pigmentation during tuber development.PMID:36818280 | PMC:PMC9932491 | DOI:10.1016/j.isci.2022.105903

Comput Struct Biotechnol J. 2023 Jan 31;21:1236-1248. doi: 10.1016/j.csbj.2023.01.041. eCollection 2023.ABSTRACTIsovaleric acidemia (IVA), due to isovaleryl-CoA dehydrogenase (IVD) deficiency, results in the accumulation of isovaleryl-CoA, isovaleric acid and secondary metabolites. The increase in these metabolites decreases mitochondrial energy production and increases oxidative stress. This contributes to the neuropathological features of IVA. A general assumption in the literature exists that glycine N-acyltransferase (GLYAT) plays a role in alleviating the symptoms experienced by IVA patients through the formation of N-isovalerylglycine. GLYAT forms part of the phase II glycine conjugation pathway in the liver and detoxifies excess acyl-CoA's namely benzoyl-CoA. However, very few studies support GLYAT as the enzyme that conjugates isovaleryl-CoA to glycine. Furthermore, GLYATL1, a paralogue of GLYAT, conjugates phenylacetyl-CoA to glutamine. Therefore, GLYATL1 might also be a candidate for the formation of N-isovalerylglycine. Based on the findings from the literature review, we proposed that GLYAT or GLYATL1 can form N-isovalerylglycine in IVA patients. To test this hypothesis, we performed an in-silico analysis to determine which enzyme is more likely to conjugate isovaleryl-CoA with glycine using AutoDock Vina. Thereafter, we performed in vitro validation using purified enzyme preparations. The in-silico and in vitro findings suggested that both enzymes could form N-isovaleryglycine albeit at lower affinities than their preferred substrates. Furthermore, an increase in glycine concentration does not result in an increase in N-isovalerylglycine formation. The results from the critical literature appraisal, in-silico, and in vitro validation, suggest the importance of further investigating the reaction kinetics and binding behaviors between these substrates and enzymes in understanding the pathophysiology of IVA.PMID:36817957 | PMC:PMC9932296 | DOI:10.1016/j.csbj.2023.01.041

Comput Struct Biotechnol J. 2023 Jan 31;21:1372-1382. doi: 10.1016/j.csbj.2023.01.043. eCollection 2023.ABSTRACTCancer progression is linked to gene-environment interactions that alter cellular homeostasis. The use of biomarkers as early indicators of disease manifestation and progression can substantially improve diagnosis and treatment. Large omics datasets generated by high-throughput profiling technologies, such as microarrays, RNA sequencing, whole-genome shotgun sequencing, nuclear magnetic resonance, and mass spectrometry, have enabled data-driven biomarker discoveries. The identification of differentially expressed traits as molecular markers has traditionally relied on statistical techniques that are often limited to linear parametric modeling. The heterogeneity, epigenetic changes, and high degree of polymorphism observed in oncogenes demand biomarker-assisted personalized medication schemes. Deep learning (DL), a major subunit of machine learning (ML), has been increasingly utilized in recent years to investigate various diseases. The combination of ML/DL approaches for performance optimization across multi-omics datasets produces robust ensemble-learning prediction models, which are becoming useful in precision medicine. This review focuses on the recent development of ML/DL methods to provide integrative solutions in discovering cancer-related biomarkers, and their utilization in precision medicine.PMID:36817954 | PMC:PMC9929204 | DOI:10.1016/j.csbj.2023.01.043

Front Public Health. 2023 Feb 1;11:1103022. doi: 10.3389/fpubh.2023.1103022. eCollection 2023.ABSTRACTBACKGROUND: Excessive doses of electromagnetic radiation pose a negative impact on the central nervous system and lead to mental disorders. Molecular hydrogen can scavenge intracellular hydroxyl radicals, acting as an antioxidant, anti-apoptotic and anti-inflammatory agent. We seek to assess the capability of molecular hydrogen to ameliorate brain damage induced by electromagnetic radiation.METHODS: NEMP (nuclear electromagnetic pulse), a subset of electromagnetic pulse with high voltage value that could cause severe brain injury, was applied to this study. Male wild-type rats were divided into four groups: the control group, the H2 (Molecular hydrogen) group, the NEMP group and the NEMP+H2 group. Rats in the H2 group and the NEMP+H2 group were fed with saturated hydrogen-rich water from 3 days before NEMP exposure (electromagnetic field intensity 400 kV/m, rising edge 20 ns and pulse width 200 ns) to the day of sacrifice. One day after exposure, animal behavior experiments were performed, and samples for transcriptomics and metabolomics analysis were collected. Seven days after exposure, histopathological experiments were conducted.RESULTS: The data from the elevated plus maze and the open field test showed that NEMP exposure elicited anxiety-like behavior in rats, which could be alleviated by H2 treatment. Histopathological results manifested that NEMP exposure-induced injuries of the neurons in the hippocampus and amygdala could be attenuated by H2 treatment. Transcriptomic results revealed that NEMP exposure had a profound effect on microtubule structure in the brain. And the combined analysis of transcriptomics and metabolomics showed that H2 has a significant impact on the neuroactive ligand-receptor interaction, synaptic vesicle cycle and synapse etc. Moreover, it was indicated that the glutathione metabolic pathway played a vital role in the NEMP exposure-induced damage and the protective activity of H2.CONCLUSIONS: H2 is identified as a potent agent against NEMP exposure-induced brain damage and has the potential to be a promising electromagnetic radiation protectant.PMID:36817910 | PMC:PMC9929151 | DOI:10.3389/fpubh.2023.1103022

Front Cell Infect Microbiol. 2023 Feb 2;12:1017165. doi: 10.3389/fcimb.2022.1017165. eCollection 2022.ABSTRACTCyprinid herpesvirus 2 (CyHV-2) infects gibel carp (Carassius auratus gibelio) and causes severe losses. Microbiota in animal guts involves nutrition intake, development, immunity, and disease resistance. However, the relationship between gibel carp gut microbiota and CyHV-2 infection is not well known. Herein, we analyzed the gut microbiota composition and metabolite profiles in CyHV-2-infected and -uninfected fish using high-throughput sequencing and gas chromatography/mass spectrometry. Results showed that CyHV-2 infection significantly changed gut microbiota and metabolite profiles (p < 0.05). High-throughput sequencing demonstrated that the relative abundance of Aeromonas in the midgut increased dramatically while Cetobacterium decreased. Time-course analysis showed that the number of Aeromonas in the midgut of infected fish increased more than 1,000 times within 5 days post infection. Metabolome analysis illustrated that CyHV-2 infection significantly altered 24 metabolites in the midgut of gibel carp, annotating to the anomaly of digestion and metabolisms of amino acids, carbohydrates, and lipids, such as tryptophan (Trp) metabolism. The Mantel test demonstrated that gut microbiota and metabolite profiles were well related (r = 0.89). Furthermore, Trp metabolism responded to CyHV-2 infection closely was taken as one example to prove the correlation among CyHV-2 infection, metabolites and microbiota in the midgut, and host immunity. Results showed that modulating Trp metabolism could affect the relative abundance of Aeromonas in the midgut of fish, transcription of antiviral cytokines, and CyHV-2 infection. Therefore, we can conclude that CyHV-2 infection significantly perturbed the gut microbiome, disrupted its' metabolic functions, and caused the proliferation of the opportunistic pathogen Aeromonas. This study also suggests that modulation of the gut microbiome will open a therapeutic opportunity to control CyHV-2 infection in gibel carp.PMID:36817692 | PMC:PMC9933507 | DOI:10.3389/fcimb.2022.1017165

Front Endocrinol (Lausanne). 2023 Feb 1;14:1131256. doi: 10.3389/fendo.2023.1131256. eCollection 2023.ABSTRACTWell-controlled metabolism is the prerequisite for optimal oocyte development. To date, numerous studies have focused mainly on the utilization of exogenous substrates by oocytes, whereas the underlying mechanism of intrinsic regulation during meiotic maturation is less characterized. Herein, we performed an integrated analysis of parallel metabolomics and transcriptomics by isolating porcine oocytes at three time points, cooperatively depicting the global picture of the metabolic patterns during maturation. In particular, we identified the novel metabolic features during porcine oocyte meiosis, such as the fall in bile acids, the active one-carbon metabolism and a progressive decline in nucleotide metabolism. Collectively, the current study not only provides a comprehensive multiple omics data resource, but also may facilitate the discovery of molecular biomarkers that could be used to predict and improve oocyte quality.PMID:36817597 | PMC:PMC9929430 | DOI:10.3389/fendo.2023.1131256

Brain Behav Immun Health. 2023 Jan 31;28:100599. doi: 10.1016/j.bbih.2023.100599. eCollection 2023 Mar.ABSTRACTBaicalein (BE) has both antioxidant and anti-inflammatory effects. It has also been reported able to improve cerebral blood circulation in brain ischemic injury. However, its chronic efficacy and metabolomics in Alzheimer's disease (AD) remain unknown. In this study, BE at 80 mg/kg was administrated through the oral route in J20 AD transgenic mice aged from aged 4 months to aged 10 months. Metabolic- and neurobehavioural phenotyping was done before and after 6 months' treatment to evaluate the drug efficacy and the relevant mechanisms. Meanwhile, molecular docking was used to study the binding affinity of BE and poly (ADP-ribose) polymerase-1 (PARP-1) which is related to neuronal injury. The open field test showed that BE could suppress hyperactivity in J20 mice and increase the frequency of the target quadrant crossing in the Morris Water Maze test. More importantly, BE restored cerebral blood flow back to the normal level after the chronic treatment. A 1H NMR-based metabolomics study showed that BE treatment could restore the tricarboxylic acid cycle in plasma. And such a treatment could suppress oxidative stress, inhibit neuroinflammation, alleviate mitochondrial dysfunction, improve neurotransmission, and restore amino homeostasis via starch and sucrose metabolism and glycolipid metabolism in the cortex and hippocampus, which could affect the behavioural and cerebral blood flow. These findings showed that BE is a potential therapeutic agent for AD.PMID:36817510 | PMC:PMC9931920 | DOI:10.1016/j.bbih.2023.100599

ARYA Atheroscler. 2022 Jul;18(4):1-10. doi: 10.22122/arya.2022.26215.ABSTRACTMetabolic syndrome (MetS) is one of the most important health issues around the world and a major risk factor for both type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The etiology of MetS is determined by the interaction between genetic and environmental factors. Effective prevention and treatment of MetS notably decreases the risk of its complications such as diabetes, obesity, hypertension, and dyslipidemia. According to recent genome-wide association studies, multiple genes are involved in the incidence and development of MetS. The presence of particular genes which are responsible for obesity and lipid metabolism, affecting insulin sensitivity and blood pressure, as well as genes associated with inflammation, can increase the risk of MetS. These molecular markers, together with clinical data and findings from proteomic, metabolomic, pharmacokinetic, and other methods, would clarify the etiology and pathophysiology of MetS and facilitate the development of personalized approaches to the management of MetS. The application of personalized medicinebased on susceptibility identified genomes would help physicians recommend healthier lifestyles and prescribe medications to improve various aspects of health in patients with MetS. In recent years, personalized medicine by genetic testing has helped physicians determine genetic predisposition to MetS, prevent the disease by behavioral, lifestyle-related, or therapeutic interventions, and detect, diagnose, treat, and manage the disease. Clinically, personalized medicine is providing effective strategies for the prevention and treatment of MetS by reducing the time, cost, and failure rate of pharmaceutical clinical trials. It is also eliminating trial-and-error inefficiencies that inflate health care costs and undermine patient care.PMID:36817343 | PMC:PMC9937665 | DOI:10.22122/arya.2022.26215

Front Pharmacol. 2023 Feb 3;14:1135791. doi: 10.3389/fphar.2023.1135791. eCollection 2023.NO ABSTRACTPMID:36817158 | PMC:PMC9937692 | DOI:10.3389/fphar.2023.1135791

Front Oncol. 2023 Feb 3;13:986788. doi: 10.3389/fonc.2023.986788. eCollection 2023.ABSTRACTINTRODUCTION: Amino-acid positron emission tomography (PET) is a validated metabolic imaging approach for the diagnostic work-up of gliomas. This study aimed to evaluate sex-specific radiomic characteristics of L-[S-methyl-11Cmethionine (MET)-PET images of glioma patients in consideration of the prognostically relevant biomarker isocitrate dehydrogenase (IDH) mutation status.METHODS: MET-PET of 35 astrocytic gliomas (13 females, mean age 41 ± 13 yrs. and 22 males, mean age 46 ± 17 yrs.) and known IDH mutation status were included. All patients underwent radiomic analysis following imaging biomarker standardization initiative (IBSI)-conform guidelines both from standardized uptake value (SUV) and tumor-to-background ratio (TBR) PET values. Aligned Monte Carlo (MC) 100-fold split was utilized for SUV and TBR dataset pairs for both sex and IDH-specific analysis. Borderline and outlier scores were calculated for both sex and IDH-specific MC folds. Feature ranking was performed by R-squared ranking and Mann-Whitney U-test together with Bonferroni correction. Correlation of SUV and TBR radiomics in relation to IDH mutational status in male and female patients were also investigated.RESULTS: There were no significant features in either SUV or TBR radiomics to distinguish female and male patients. In contrast, intensity histogram coefficient of variation (ih.cov) and intensity skewness (stat.skew) were identified as significant to predict IDH +/-. In addition, IDH+ females had significant ih.cov deviation (0.031) and mean stat.skew (-0.327) differences compared to IDH+ male patients (0.068 and -0.123, respectively) with two-times higher standard deviations of the normal brain background MET uptake as well.DISCUSSION: We demonstrated that female and male glioma patients have significantly different radiomic profiles in MET PET imaging data. Future IDH prediction models shall not be built on mixed female-male cohorts, but shall rely on sex-specific cohorts and radiomic imaging biomarkers.PMID:36816966 | PMC:PMC9936222 | DOI:10.3389/fonc.2023.986788

Food Technol Biotechnol. 2022 Dec;60(4):469-487. doi: 10.17113/ftb.60.04.22.7561.ABSTRACTRESEARCH BACKGROUND: Sparassis latifolia polysaccharides can regulate lipids and cholesterol in serum and liver. However, little is known about the regulation mechanism of the polysaccharides on cholesterol metabolism and especially the causal relationship with gut microbiota regulation. This study will provide a theoretical basis for the cholesterol-lowering mechanism of S. latifolia polysaccharides and further development of functional foods.EXPERIMENTAL APPROACH: In this study, we investigated how the regulation mechanism of Sparassis latifolia polysaccharides affects intestinal cholesterol metabolism in high-fat and high-cholesterol diet-fed rats. Briefly, enzymatic colorimetric microplate assay was used to determine the concentration of faecal bile acid. Gas chromatography-mass spectrometry was used to detect the content of cholesterol and alcohol in faeces. Haematoxylin and eosin staining method was applied to observe the changes in the structure of the small intestine tissue. The related gene expressions in jejunum and ileum were detected by real-time fluorescent quantitative polymerase chain reaction. The related protein expressions in jejunum were studied by using Western blot. High-throughput sequencing was used to detect the intestinal flora changes of the caecal contents. Gas chromatography-mass spectrometry was applied to detect the concentration of short-chain fatty acids in the caecal content.RESULTS AND CONCLUSIONS: The results showed that Sparassis latifolia polysaccharides could improve the intestinal morphological structure and physiological indices in rats fed high-fat and high-cholesterol diet. Moreover, it could improve intestinal cholesterol metabolism disorder induced by high-fat and high-cholesterol diets via the reduction of the expression of HMGCR, NPC1L1, ACAT2, MTP, ASBT and IBABP mRNA or protein, increasing ABCG8 mRNA expression. In addition, it could also increase the relative abundance of Bacteroides, Butyricicoccus, Parabacteroides, Parasutteerella and Alloprevotella and the short-chain fatty acid concentration, to comprehensively regulate the intestinal cholesterol metabolism. The metabolomics analysis found that Sparassis latifolia polysaccharides could affect lipid, carbohydrate and other related metabolites. Some biomarkers associated with cholesterol metabolism correlated significantly with the abundance of specific intestinal microbiota.NOVELTY AND SCIENTIFIC CONTRIBUTION: These findings indicate that Sparassis latifolia polysaccharides could attenuate intestinal cholesterol metabolism disorder, correlating with modulating gut microbiota and improving host metabolism. They provide theoretical support for the development of Sparassis latifolia as a new food resource.PMID:36816874 | PMC:PMC9901340 | DOI:10.17113/ftb.60.04.22.7561