PubMed

Front Neurol. 2023 Mar 9;14:1090631. doi: 10.3389/fneur.2023.1090631. eCollection 2023.ABSTRACTINTRODUCTION: Multiple sclerosis (MS), a non-contagious and chronic disease of the central nervous system, is an unpredictable and indirectly inherited disease affecting different people in different ways. Using Omics platforms genomics, transcriptomics, proteomics, epigenomics, interactomics, and metabolomics database, it is now possible to construct sound systems biology models to extract full knowledge of the MS and recognize the pathway to uncover the personalized therapeutic tools.METHODS: In this study, we used several Bayesian Networks in order to find the transcriptional gene regulation networks that drive MS disease. We used a set of BN algorithms using the R add-on package bnlearn. The BN results underwent further downstream analysis and were validated using a wide range of Cytoscape algorithms, web based computational tools and qPCR amplification of blood samples from 56 MS patients and 44 healthy controls. The results were semantically integrated to improve understanding of the complex molecular architecture underlying MS, distinguishing distinct metabolic pathways and providing a valuable foundation for the discovery of involved genes and possibly new treatments.RESULTS: Results show that the LASP1, TUBA1C, and S100A6 genes were most likely playing a biological role in MS development. Results from qPCR showed a significant increase (P < 0.05) in LASP1 and S100A6 gene expression levels in MS patients compared to that in controls. However, a significant down regulation of TUBA1C gene was observed in the same comparison.CONCLUSION: This study provides potential diagnostic and therapeutic biomarkers for enhanced understanding of gene regulation underlying MS.PMID:36970516 | PMC:PMC10035600 | DOI:10.3389/fneur.2023.1090631

J Tradit Complement Med. 2022 Sep 27;13(2):170-182. doi: 10.1016/j.jtcme.2022.09.001. eCollection 2023 Mar.ABSTRACTBACKGROUND AND AIM: Qingfei Jiedu Granules (QFJD) are a new Traditional Chinese Medicine (TCM) which has been clinically used against coronavirus pneumonia in China. In this study, the therapeutic effect and the underlying mechanisms of QFJD against influenza were investigated.EXPERIMENTAL PROCEDURE: Pneumonia mice were induced by influenza A virus. Survival rate, weight loss, lung index and lung pathology were measured to evaluate the therapeutic effect of QFJD. The expression of inflammatory factors and lymphocytes was used to assess anti-inflammatory and immunomodulatory effect of QFJD. Gut microbiome analysis was performed to decipher the potential effect of QFJD on intestinal microbiota. Metabolomics approach was conducted to explore the overall metabolic regulation of QFJD.RESULT AND CONCLUSION: QFJD shows a significant therapeutic effect on the treatment of influenza and the expression of many pro-inflammatory cytokines were obviously inhibited. QFJD also markedly modulates the level of T and B lymphocytes. The high-dose QFJD has shown similar therapeutic efficiency compared to positive drugs. QFJD profoundly enriched Verrucomicrobia and maintained the balance between Bacteroides and Firmicutes. QFJD associated with 12 signaling pathways in metabolomics study, 9 of which were the same as the model group and were closely related to citrate cycle and amino acid metabolism.To sum up, QFJD is a novel and promising drug against influenza. It can regulate inflammation, immunity, metabolism, and gut microbiota to fight influenza. Verrucomicrobia shows great potential to improve influenza infection and may be an important target.PMID:36970461 | PMC:PMC10037062 | DOI:10.1016/j.jtcme.2022.09.001

J Tradit Complement Med. 2023 Feb 28;13(2):207-217. doi: 10.1016/j.jtcme.2023.02.011. eCollection 2023 Mar.ABSTRACTTriphala is a mixture of tree fruits obtained from Terminalia chebula, Terminalia bellerica, and Phyllanthus emblica. It is one of the Ayurveda medicinal recipes used to treat health diseases such as obesity. The chemical composition analysis of Triphala extracts obtained from an equal portion of three fruits was performed. The contents of total phenolic compounds (62.87 ± 0.21 mg gallic acid equivalent/mL), total flavonoids (0.24 ± 0.01 mg catechin equivalent/mL), hydrolyzable tannins (177.27 ± 10.09 mg gallotannin equivalent/mL), and condensed tannins (0.62 ± 0.11 mg catechin equivalent/mL) were observed in Triphala extracts. The 1 mg/mL of Triphala extracts was applied to batch culture fermentation which contained the feces from voluntarily obese female adults (body mass index of 35.0-40.0 kg/m2) for 24 h. The extraction of DNA and metabolites was each conducted on the samples obtained from batch culture fermentation within and without Triphala extracts treatment. The 16S rRNA gene sequencing and untargeted metabolomic analysis were carried out. There was no statistically significant difference between Triphala extracts and control treatments on the changes in microbial profiles (p-value <0.05). While the metabolomic analysis showed statistically significant differences of 305 up-regulated and 23 down-regulated metabolites in the treatment of Triphala extracts when compared with the control (p-value <0.05 and fold-change ≥2) belonging to 60 pathways. The pathway analysis revealed that Triphala extracts play an important role in the activation of phenylalanine, tyrosine and tryptophan biosynthesis. In this study, phenylalanine and tyrosine were identified metabolites which involve in the regulation of energy metabolism. The treatment of Triphala extracts possesses the induction of phenylalanine, tyrosine and tryptophan biosynthesis in fecal batch culture fermentation of obese adults and therefore it can be suggested as a probable herbal medicinal recipe for obesity treatment.PMID:36970454 | PMC:PMC10037071 | DOI:10.1016/j.jtcme.2023.02.011

Front Cardiovasc Med. 2023 Mar 10;10:1037357. doi: 10.3389/fcvm.2023.1037357. eCollection 2023.ABSTRACTPulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a severely progressive condition with uncertain physiological course. Hence, it has become increasingly relevant to clarify the specific mechanisms of molecular modification, which is crucial to identify more treatment strategies. With the rapid development of high-throughput sequencing, omics technology gives access to massive experimental data and advanced techniques for systems biology, permitting comprehensive assessment of disease occurrence and progression. In recent years, significant progress has been made in the study of PAH-CHD and omics. To provide a comprehensive description and promote further in-depth investigation of PAH-CHD, this review attempts to summarize the latest developments in genomics, transcriptomics, epigenomics, proteomics, metabolomics, and multi-omics integration.PMID:36970344 | PMC:PMC10036813 | DOI:10.3389/fcvm.2023.1037357

Front Cardiovasc Med. 2023 Mar 10;10:1147438. doi: 10.3389/fcvm.2023.1147438. eCollection 2023.ABSTRACTBACKGROUND: Heart failure (HF) is a syndrome with global clinical and socioeconomic burden worldwide owing to its poor prognosis. Jiashen Prescription (JSP), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating HF. Previously, we have reported that underlying mechanisms of JSP by an untargeted metabolomics approach, but the contribution of gut microbiota and metabolic interaction to the cardioprotective efficacy of JSP remains to be elucidated.MATERIALS AND METHODS: Firstly, the rat model of heart failure was established by the permanent ligation of the left anterior descending coronary artery. The efficacy evaluation of JSP in treating HF rats was per-formed by left ventricular ejection fraction (LVEF). Then, 16S rRNA gene sequencing and LC/MS-based metabolomic analysis were utilized to explore the characteristics of cecal-contents microecology and plasma metabolic profile, respectively. After that, the correlation between intestinal micro-ecological characteristics and plasma metabolic characteristics was analyzed to explore the potential mechanism of the JSP treatment in HF.RESULTS: JSP could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat LVEF. Results of intestinal flora analysis revealed that JSP not only adjusted gut microbiota disturbances by enriching species diversity, reducing the abundance of pathogenic bacteria (such as Allobaculum, Brevinema), as well as increasing the abundance of beneficial bacteria (such as Lactobacillus, Lachnospiraceae_NK4A136_group), but also improved metabolic disorders by reversing metabolite plasma levels to normality. Through the conjoint analysis of 8 metabolites and the OTUs relative abundance data in the 16srRNA sequencing results by WGCNA method, 215 floras significantly related to the eight compounds were identified. The results of the correlation analysis demonstrated a significant association between intestinal microbiota and plasma metabolic profile, especially the significant correlation of Ruminococcaceae_UCG-014 and Protoporphyrin IX, Ruminococcaceae_UCG-005, Christensenellaceae_R-7_group and nicotinamide, dihydrofolic acid.CONCLUSION: The present study illustrated the underlying mechanism of JSP to treat heart failure by affecting intestinal flora and plasma metabolites, provide a potential therapeutic strategy against heart failure.PMID:36970332 | PMC:PMC10036802 | DOI:10.3389/fcvm.2023.1147438

Food Saf (Tokyo). 2023 Feb 11;11(1):1-20. doi: 10.14252/foodsafetyfscj.D-22-00010. eCollection 2023 Mar.ABSTRACT"Transgrafting" is a grafting procedure whereby a transgenic plant body is grafted to a non-transgenic plant body. It is a novel plant breeding technology that allows non-transgenic plants to obtain benefits usually conferred to transgenic plants. Many plants regulate flowering by perceiving the day-length cycle via expression of FLOWERING LOCUS T (FT) in the leaves. The resulting FT protein is translocated to the shoot apical meristem via the phloem. In potato plants, FT is involved in the promotion of tuber formation. Here we investigated the effects of a genetically modified (GM) scion on the edible parts of the non-GM rootstock by using potato plants transformed with StSP6A, a novel potato homolog of the FT gene. Scions prepared from GM or control (wild-type) potato plants were grafted to non-GM potato rootstocks; these were designated as TN and NN plants, respectively. After tuber harvest, we observed no significant differences in potato yield between TN and NN plants. Transcriptomic analysis revealed that only one gene-with unknown function-was differentially expressed between TN and NN plants. Subsequent proteomic analysis indicated that several members of protease inhibitor families, known as anti-nutritional factors in potato, were slightly more abundant in TN plants. Metabolomic analysis revealed a slight increase in metabolite abundance in NN plants, but we observed no difference in the accumulation of steroid glycoalkaloids, toxic metabolites found in potato. Finally, we found that TN and NN plants did not differ in nutrient composition. Taken together, these results indicate that FT expression in scions had a limited effect on the metabolism of non-transgenic potato tubers.PMID:36970308 | PMC:PMC10034357 | DOI:10.14252/foodsafetyfscj.D-22-00010

Oncoimmunology. 2023 Mar 21;12(1):2189823. doi: 10.1080/2162402X.2023.2189823. eCollection 2023.ABSTRACTFormyl peptide receptor-1 (FPR1) is a pathogen recognition receptor involved in the detection of bacteria, in the control of inflammation, as well as in cancer immunosurveillance. A single nucleotide polymorphism in FPR1, rs867228, provokes a loss-of-function phenotype. In a bioinformatic study performed on The Cancer Genome Atlas (TCGA), we observed that homo-or heterozygosity for rs867228 in FPR1 (which affects approximately one-third of the population across continents) accelerates age at diagnosis of specific carcinomas including luminal B breast cancer by 4.9 years. To validate this finding, we genotyped 215 patients with metastatic luminal B mammary carcinomas from the SNPs To Risk of Metastasis (SToRM) cohort. The first diagnosis of luminal B breast cancer occurred at an age of 49.2 years for individuals bearing the dysfunctional TT or TG alleles (n = 73) and 55.5 years for patients the functional GG alleles (n = 141), meaning that rs867228 accelerated the age of diagnosis by 6.3 years (p=0.0077, Mann & Whitney). These results confirm our original observation in an independent validation cohort. We speculate that it may be useful to include the detection of rs867228 in breast cancer screening campaigns for selectively increasing the frequency and stringency of examinations starting at a relatively young age.PMID:36970071 | PMC:PMC10038022 | DOI:10.1080/2162402X.2023.2189823

Front Pharmacol. 2023 Mar 9;14:1087654. doi: 10.3389/fphar.2023.1087654. eCollection 2023.ABSTRACTBackground: Curcumae Radix (CW) is traditionally used to treat primary dysmenorrea (PD). However, the mechanisms of action of CW in the treatment of PD have not yet been comprehensively resolved. Objective: To investigate the therapeutic effects of CW on PD and its possible mechanisms of action. Methods: An isolated uterine spastic contraction model induced by oxytocin was constructed in an in vitro pharmacodynamic assay. An animal model of PD induced by combined estradiol benzoate and adrenaline hydrochloride-assisted stimulation was established. After oral administration of CW, a histopathological examination was performed and biochemical factor levels were measured to evaluate the therapeutic effect of CW on PD. The chemical compositions of the drug-containing serum and its metabolites were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Network pharmacology and serum untargeted metabolomics were used to predict the mechanism of CW treatment for PD, and the predicted results were validated by RT-qPCR, WB, and targeted fatty acid (FA) metabolism. Results: In vitro, CW can relax an isolated uterus by reducing uterine motility. In vivo, the results showed that CW attenuated histopathological damage in the uterus and regulated PGF2α, PGE2, β-EP, 5-HT, and Ca2+ levels in PD rats. A total of 66 compounds and their metabolites were identified in the drug-containing serum, and the metabolic pathways of these components mainly included hydrogenation and oxidation. Mechanistic studies showed that CW downregulated the expression of key genes in the 5-HTR/Ca2+/MAPK pathway, such as 5-HTR2A, IP3R, PKC, cALM, and ERK. Similarly, CW downregulated the expression of key proteins in the 5-HTR/Ca2+/MAPK pathway, such as p-ERK/ERK. Indirectly, it ameliorates the abnormal FA metabolism downstream of this signaling pathway in PD rats, especially the metabolism of arachidonic acid (AA). Conclusion: The development of PD may be associated with the inhibition of the 5-HTR/Ca2+/MAPK signaling pathway and FA metabolic pathways, providing a basis for the subsequent exploitation of CW.PMID:36969877 | PMC:PMC10034069 | DOI:10.3389/fphar.2023.1087654

Front Pharmacol. 2023 Mar 9;14:1134429. doi: 10.3389/fphar.2023.1134429. eCollection 2023.ABSTRACTIntroduction: Cordyceps militaris, which has many potential medicinal properties, has rarely been reported to alleviate type 2 diabetes mellitus (T2DM). Methods: The effects of C. militaris extracts (CE) and cordycepin (CCS) on high-fat diet and streptozotocin (STZ) induced T2DM mice were analysed by gut microbiome and metabolomics methods in this study. Results: The results demonstrated that glucose and lipid metabolism parameters, oxidative stress biomarkers and inflammation cytokines were down-regulated in the CCS and CE groups. A comparative analysis of the fecal samples from mice in the model and experimental groups showed that experimental groups resulted in a higher abundance of Firmicutes/Bacteroidetes. Conclusion: This study provides evidence that C. militaris can be used as a food supplement to relieve T2DM, which provides a promising prospect for new functional food in it.PMID:36969858 | PMC:PMC10033974 | DOI:10.3389/fphar.2023.1134429

Front Nutr. 2023 Mar 9;10:1161698. doi: 10.3389/fnut.2023.1161698. eCollection 2023.ABSTRACTINTRODUCTION: Obesity is a common nutritional disorder characterized by an excessive fat accumulation. In view of the critical role of gut microbiota in the development of obesity and metabolic diseases, novel dietary therapies have been developed to manage obesity by targeting the gut microbiome. In this study, we investigated anti-obesity effects of bamboo shoot dietary fiber (BSDF) and the potential mechanisms.METHODS: After 12 weeks of intervention with BSDF in high-fat mice, we detected obesity-related phenotypic indicators, and made transcriptomic analysis of liver tissue. Then we analyzed the changes of gut microbiota using 16S rRNA gene sequencing, explored the effect of BSDF on gut microbiota metabolites, and finally verified the importance of gut microbiota through antibiotic animal model.RESULTS AND DISCUSSION: We found that BSDF was effective in reducing lipid accumulation in liver and adipose tissue and alleviating dyslipidemia and insulin resistance. Liver transcriptome analysis results showed that BSDF could improve lipid metabolism and liver injury by modulating peroxisome proliferator-activated receptor (PPAR) and fatty acid metabolic pathways. The 16S rRNA gene sequencing analysis of gut microbiota composition showed that BSDF significantly enriched beneficial bacteria such as Bifidobacterium, Akkermansia, Dubosiella, and Alloprevotella. Analysis of fecal metabolomics and gut microbiota metabolites revealed that BSDF increased the levels of several short-chain fatty acids and enriched bile acids, which may be important for improving lipid metabolism. Notably, the obesity-related metabolic disorders were abrogated after the abrogation of gut microbiota, suggesting that gut microbiota is a key factor in the beneficial effects of BSDF.CONCLUSION: Our study suggests that BSDF as a prebiotic supplement has the potential to improve obesity by improving gut microbiota and modulating host PPAR and fatty acid metabolic pathways.PMID:36969828 | PMC:PMC10035599 | DOI:10.3389/fnut.2023.1161698

Front Nutr. 2023 Mar 9;10:1127729. doi: 10.3389/fnut.2023.1127729. eCollection 2023.ABSTRACTBACKGROUND: There is a need to better understand the relationship between the diet, the gut microbiota and mental health. Metabolites produced when the human gut microbiota metabolize amino acids may enter the bloodstream and have systemic effects. We hypothesize that fermentation of amino acids by a resistant protein-primed gut microbiota could yield potentially toxic metabolites and disturb the availability of neurotransmitter precursors to the brain. However, these mechanisms are challenging to investigate via typical in vitro and clinical methods.METHODS: We developed a novel workflow using 14C radiolabeling to investigate complex nutrient-disease relationships. The first three steps of the workflow are reported here. α-Linolenic acid (ALA) was used as a model nutrient to confirm the efficacy of the workflow, and tyrosine (Tyr) was the test nutrient. 14C-Tyr was administered to male weanling pigs fed a high resistant protein diet, which primed the gut microbiota for fermenting protein. The hypotheses were; (1) that expected biodistribution of 14C-ALA would be observed, and (2) that radioactivity from 14C-Tyr, representing Tyr and other amino acids released from resistant protein following gut microbial fermentation, would be bioavailable to the brain.RESULTS: Radioactivity from the 14C-ALA was detected in tissues reflecting normal utilization of this essential fatty acid. Radioactivity from the 14C-Tyr was detected in the brain (0.15% of original dose).CONCLUSION: Metabolites of gut-fermented protein and specifically amino acid precursors to neurotransmitters such as tyrosine, are potentially able to affect brain function. By extension, resistant proteins in the diet reaching the gut microbiota, also have potential to release metabolites that can potentially affect brain function. The high specificity of detection of 14C radioactivity demonstrates that the proposed workflow can similarly be applied to understand other key diet and health paradigms.PMID:36969812 | PMC:PMC10033698 | DOI:10.3389/fnut.2023.1127729

Biofilm. 2023 Mar 12;5:100112. doi: 10.1016/j.bioflm.2023.100112. eCollection 2023 Dec.ABSTRACTCandida albicans is the most prevalent and notorious of the Candida species involved in bloodstream infections, which is characterised by its capacity to form robust biofilms. Biofilm formation is an important clinical entity shown to be highly variable among clinical isolates. There are various environmental and physiological factors, including nutrient availability which influence the phenotype of Candida species. However, mechanisms underpinning adaptive biofilm heterogeneity have not yet been fully explored. Within this study we have profiled previously characterised and phenotypically distinct C. albicans bloodstream isolates. We assessed the dynamic susceptibility of these differing populations to antifungal treatments using population analysis profiling in addition to assessing biofilm formation and morphological changes. High throughput methodologies of RNA-Seq and LC-MS were employed to map and integrate the transcriptional and metabolic reprogramming undertaken by heterogenous C. albicans isolates in response to biofilm and hyphal inducing serum. We found a significant relationship between biofilm heterogeneity and azole resistance (P < 0.05). In addition, we observed that in response to serum our low biofilm forming (LBF) C. albicans exhibited a significant increase in biofilm formation and hyphal elongation. The transcriptional reprogramming of LBF strains compared to high biofilm forming (HBF) was distinct, indicating a high level of plasticity and variation in stress responses by heterogenous strains. The metabolic responses, although variable between LBF and HBF, shared many of the same responses to serum. Notably, a high upregulation of the arachidonic acid cascade, part of the COX pathway, was observed and this pathway was found to induce biofilm formation in LBF 3-fold. C. albicans is a highly heterogenous bloodstream pathogen with clinical isolates varying in antifungal tolerance and biofilm formation. In addition to this, C. albicans is capable of highly complex and variable regulation of transcription and metabolic pathways and heterogeneity across isolates further increases the complexity of these pathways. Here we have shown with a dual and integrated approach, the importance of studying a diverse panel of C. albicans isolates, which has the potential to reveal distinct pathways that can harnessed for drug discovery.PMID:36969800 | PMC:PMC10034394 | DOI:10.1016/j.bioflm.2023.100112

Front Physiol. 2023 Mar 9;14:1122026. doi: 10.3389/fphys.2023.1122026. eCollection 2023.ABSTRACTHigh altitude pulmonary edema (HAPE) is a serious threat to the physical and mental health of people who quickly enter high plateaus, deserves more attention and in-depth research. In our study, through the detection of various physiological indexes and other phenotypes in a HAPE rat model, the HAPE group showed a significant decrease in oxygen partial pressure and oxygen saturation, and a significant increase in pulmonary artery pressure and lung tissue water content. The lung histomorphology showed characteristics such as pulmonary interstitial thickening and inflammatory cell infiltration. We applied quasi-targeted metabolomics to compare and analyze the components of metabolites in arterial-veinous blood in control rats and HAPE rats. Using kyoto Encyclopedia of Genes Genomes (KEGG) enrichment analysis and two machine algorithms, we speculate that after hypoxic stress and comparing arterial blood and venous blood products in rats, the metabolites were richer, indicating that normal physiological activities, such as metabolism and pulmonary circulationhad a greater impact after hypoxic stress; D-mannoseDOWN, oxidized glutathioneDOWN, glutathione disulfideDOWN, and dehydrocholic acidDOWN in arterial blood play key roles in predicting the occurrence of HAPE; in venous blood, L-leucineDOWN, L-thyroxineDOWN, and cis-4-hydroxy- D-prolineDOWN may have key roles, which can be considered biomarkers of HAPE. This result provides a new perspective for the further diagnosis and treatment of plateau disease and lays a strong foundation for further research.PMID:36969595 | PMC:PMC10034721 | DOI:10.3389/fphys.2023.1122026

Front Immunol. 2023 Mar 8;14:1163419. doi: 10.3389/fimmu.2023.1163419. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fimmu.2022.950441.].PMID:36969229 | PMC:PMC10031041 | DOI:10.3389/fimmu.2023.1163419

Front Immunol. 2023 Mar 9;14:1131447. doi: 10.3389/fimmu.2023.1131447. eCollection 2023.ABSTRACTThe impacts of metabolomic changes (reduced short-chain-fatty acids; SCFAs) in uremic condition is not fully understood. Once daily Candida gavage with or without probiotics (different times of administration) for 1 week prior to bilateral nephrectomy (Bil Nep) in 8-week-old C57BL6 mice as the possible models more resemble human conditions were performed. Candida-administered Bil Nep mice demonstrated more severe conditions than Bil Nep alone as indicated by mortality (n = 10/group) and other 48 h parameters (n = 6-8/group), including serum cytokines, leaky gut (FITC-dextran assay, endotoxemia, serum beta-glucan, and loss of Zona-occludens-1), and dysbiosis (increased Enterobacteriaceae with decreased diversity in microbiome analysis) (n = 3/group for fecal microbiome) without the difference in uremia (serum creatinine). With nuclear magnetic resonance metabolome analysis (n = 3-5/group), Bil Nep reduced fecal butyric (and propionic) acid and blood 3-hydroxy butyrate compared with sham and Candida-Bil Nep altered metabolomic patterns compared with Bil Nep alone. Then, Lacticaseibacillus rhamnosus dfa1 (SCFA-producing Lacticaseibacilli) (n = 8/group) attenuated the model severity (mortality, leaky gut, serum cytokines, and increased fecal butyrate) of Bil Nep mice (n = 6/group) (regardless of Candida). In enterocytes (Caco-2 cells), butyrate attenuated injury induced by indoxyl sulfate (a gut-derived uremic toxin) as indicated by transepithelial electrical resistance, supernatant IL-8, NFκB expression, and cell energy status (mitochondria and glycolysis activities by extracellular flux analysis). In conclusion, the reduced butyrate by uremia was not enhanced by Candida administration; however, the presence of Candida in the gut induced a leaky gut that was attenuated by SCFA-producing probiotics. Our data support the use of probiotics in uremia.PMID:36969207 | PMC:PMC10034098 | DOI:10.3389/fimmu.2023.1131447

Front Immunol. 2023 Mar 9;14:1134369. doi: 10.3389/fimmu.2023.1134369. eCollection 2023.ABSTRACTBACKGROUND: Peptic ulcer disease (PUD) is a multi-cause illness with an unknown role for gastric flora and metabolism in its pathogenesis. In order to further understand the pathogenesis of gastric flora and metabolism in PUD, this study used histological techniques to analyze the microbiome and metabolome of gastric biopsy tissue. In this paper, our work described the complex interactions of phenotype-microbial-metabolite-metabolic pathways in PUD patients at different pathological stages.METHODS: Gastric biopsy tissue samples from 32 patients with chronic non-atrophic gastritis, 24 patients with mucosal erosions, and 8 patients with ulcers were collected for the microbiome. UPLC-MS metabolomics was also used to detect gastric tissue samples. These datasets were analyzed individually and integrated using various bioinformatics methods.RESULTS: Our work found reduced diversity of gastric flora in patients with PUD. PUD patients at different pathological stages presented their own unique flora, and there were significant differences in flora phenotypes. Coprococcus_2, Phenylobacterium, Candidatus_Hepatoplasma, and other bacteria were found in the flora of people with chronic non-atrophic gastritis (HC). The representative flora of mucosal erosion (ME) had uncultured_bacterium_c_Subgroup_6, Sphingomonadaceae, Xanthobacteraceae, and uncultured_bacterium_f_Xanthobacteraceae. In comparison, the characteristic flora of the PUD group was the most numerous and complex, including Ruminococcus_2, Agathobacter, Alistipes, Helicobacter, Bacteroides and Faecalibacterium. Metabolomics identified and annotated 66 differential metabolites and 12 significantly different metabolic pathways. The comprehensive analysis correlated microorganisms with metabolites at different pathological stages and initially explored the complex interactions of phenotype-microbial-metabolite-metabolic pathways in PUD patients at different pathological stages.CONCLUSION: Our research results provided substantial evidence to support some data on the analysis of the microbial community and its metabolism in the stomach, and they demonstrated many specific interactions between the gastric microbiome and the metabolome. Our study can help reveal the pathogenesis of PUD and indicate plausible disease-specific mechanisms for future studies from a new perspective.PMID:36969184 | PMC:PMC10034094 | DOI:10.3389/fimmu.2023.1134369

Front Vet Sci. 2023 Mar 10;10:1132373. doi: 10.3389/fvets.2023.1132373. eCollection 2023.ABSTRACTFactors affecting sperm freezability in goat seminal plasma were investigated. Based on the total motility of thawed sperm, goats were divided into a high-freezability (HF) group with >60% total motility (n = 8) and a low-freezability (LF) group with <45% total motility (n = 8). Sperm and seminal plasma from the HF and LF groups were separated, HF seminal plasma was mixed with LF spermatozoa, LF seminal plasma was mixed with HF sperm, and the products were subjected to a freeze-thaw procedure. Semen from individual goats exhibited differences in freezability. HF semen had higher sperm motility parameters and plasma membrane and acrosome integrity after thawing; this difference could be related to the composition of seminal plasma. Seminal plasma from the HF and LF groups was evaluated using metabolomic analysis, and multivariate statistical analysis revealed a clear separation of metabolic patterns in the seminal plasma of goats with different freezability classifications. Forty-one differential metabolites were identified using the following screening conditions: variable importance in the projection > 1 and 0.05 < P-value < 0.1. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed significant enrichment of central carbon metabolism in cancer, protein digestion and absorption, aminoacyl-tRNA, and other pathways and significant differences in the abundance of seven differential metabolites, including L-glutamine, L-aspartate, L-arginine, phenylpyruvate, benzoic acid, ketoisocaproic acid, and choline between seminal plasma from the HF and LF groups (P-value < 0.05). These significantly differentially-expressed metabolites may be potential biomarkers for sperm freezability. L-glutamine, L-aspartate, and L-arginine may directly affect sperm freezability. Benzoic acid, ketoisocaproic acid, and choline may regulate sperm freezability by participating in anabolic processes involving phenylalanine, leucine, and phosphatidylcholine in sperm.PMID:36968471 | PMC:PMC10036599 | DOI:10.3389/fvets.2023.1132373

Front Plant Sci. 2023 Mar 8;14:1132024. doi: 10.3389/fpls.2023.1132024. eCollection 2023.ABSTRACTINTRODUCTION: Oil palm is the world's highest yielding oil crop and its palm oil has high nutritional value, making it an oilseed plant with important economic value and application prospects. After picking, oil palm fruits exposed to air will gradually become soft and accelerate the process of fatty acid rancidity, which will not only affect their flavor and nutritional value, but also produce substances harmful to the human body. As a result, studying the dynamic change pattern of free fatty acids and important fatty acid metabolism-related regulatory genes during oil palm fatty acid rancidity can provide a theoretical basis for improving palm oil quality and extending its shelf life.METHODS: The fruit of two shell types of oil palm, Pisifera (MP) and Tenera (MT), were used to study the changes of fruit souring at different times points of postharvesting, combined with LC-MS/MS metabolomics and RNA-seq transcriptomics techniques to analyze the dynamic changes of free fatty acids during fruit rancidity, and to find out the key enzyme genes and proteins in the process of free fatty acid synthesis and degradation according to metabolic pathways.RESULTS AND DISCUSSION: Metabolomic study revealed that there were 9 different types of free fatty acids at 0 hours of postharvest, 12 different types of free fatty acids at 24 hours of postharvest, and 8 different types of free fatty acids at 36 hours of postharvest. Transcriptomic research revealed substantial changes in gene expression between the three harvest phases of MT and MP. Combined metabolomics and transcriptomics analysis results show that the expression of SDR, FATA, FATB and MFP four key enzyme genes and enzyme proteins in the rancidity of free fatty acids are significantly correlated with Palmitic acid, Stearic acid, Myristic acid and Palmitoleic acid in oil palm fruit. In terms of binding gene expression, the expression of FATA gene and MFP protein in MT and MP was consistent, and both were expressed higher in MP. FATB fluctuates unevenly in MT and MP, with the level of expression growing steadily in MT and decreasing in MP before increasing. The amount of SDR gene expression varies in opposite directions in both shell types. The above findings suggest that these four enzyme genes and enzyme proteins may play an important role in regulating fatty acid rancidity and are the key enzyme genes and enzyme proteins that cause differences in fatty acid rancidity between MT and MP and other fruit shell types. Additionally, differential metabolite and differentially expressed genes were present in the three postharvest times of MT and MP fruits, with the difference occurring 24 hours postharvest being the most notable. As a result, 24 hours postharvest revealed the most obvious difference in fatty acid tranquility between MT and MP shell types of oil palm. The results from this study offer a theoretical underpinning for the gene mining of fatty acid rancidity of various oil palm fruit shell types and the enhancement of oilseed palm acid-resistant germplasm cultivation using molecular biology methods.PMID:36968425 | PMC:PMC10030942 | DOI:10.3389/fpls.2023.1132024

Front Plant Sci. 2023 Mar 10;14:1131708. doi: 10.3389/fpls.2023.1131708. eCollection 2023.ABSTRACTPotassium (K) is one of the most important macronutrients for plant development and growth. The influence mechanism of different potassium stresses on the molecular regulation and metabolites of apple remains largely unknown. In this research, physiological, transcriptome, and metabolite analyses were compared under different K conditions in apple seedlings. The results showed that K deficiency and excess conditions influenced apple phenotypic characteristics, soil plant analytical development (SPAD) values, and photosynthesis. Hydrogen peroxide (H2O2) content, peroxidase (POD) activity, catalase (CAT) activity, abscisic acid (ABA) content, and indoleacetic acid (IAA) content were regulated by different K stresses. Transcriptome analysis indicated that there were 2,409 and 778 differentially expressed genes (DEGs) in apple leaves and roots under K deficiency conditions in addition to 1,393 and 1,205 DEGs in apple leaves and roots under potassium excess conditions, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that the DEGs were involved in flavonoid biosynthesis, photosynthesis, and plant hormone signal transduction metabolite biosynthetic processes in response to different K conditions. There were 527 and 166 differential metabolites (DMAs) in leaves and roots under low-K stress as well as 228 and 150 DMAs in apple leaves and roots under high-K stress, respectively. Apple plants regulate carbon metabolism and the flavonoid pathway to respond to low-K and high-K stresses. This study provides a basis for understanding the metabolic processes underlying different K responses and provides a foundation to improve the utilization efficiency of K in apples.PMID:36968411 | PMC:PMC10036783 | DOI:10.3389/fpls.2023.1131708

Front Plant Sci. 2023 Mar 9;14:1155297. doi: 10.3389/fpls.2023.1155297. eCollection 2023.ABSTRACTThe aim of this study was to determine intra- and interspecies variation in the qualitative and quantitative composition of methanol-soluble metabolites in the leaves of three Digitalis species (D. lanata, D. ferruginea, and D. grandiflora) from the central Balkans. Despite the steady use of foxglove constituents for human health as valuable medicinal products, populations of the genus Digitalis (Plantaginaceae) have been poorly investigated to describe their genetic and phenetic variation. Following untargeted profiling using UHPLC-LTQ Orbitrap MS, by which we identified a total of 115 compounds, 16 compounds were quantified using the UHPLC(-)HESI-QqQ-MS/MS approach. In total, 55 steroid compounds, 15 phenylethanoid glycosides, 27 flavonoids, and 14 phenolic acid derivatives were identified across the samples with D. lanata and D. ferruginea showing a great similarity, while 15 compounds were characteristic only for D. grandiflora. The phytochemical composition of methanol extracts, considered here as complex phenotypes, are further examined along multiple levels of biological organization (intra- and interpopulation) and subsequently subjected to chemometric data analysis. The quantitative composition of the selected set of 16 chemomarkers belonging to the classes of cardenolides (3 compounds) and phenolics (13 compounds) pointed to considerable differences between the taxa studied. D. grandiflora and D. ferruginea were found to be richer in phenolics as compared to cardenolides, which otherwise predominate in D. lanata over other compounds. PCA revealed lanatoside C, deslanoside, hispidulin, and p-coumaric acid to be the main compounds contributing to the differences between D. lanata on one side and D. grandiflora and D. ferruginea on the other, while p-coumaric acid, hispidulin, and digoxin contribute to the diversification between D. grandiflora and D. ferruginea. However, quantitative variation in the metabolite content within species was faint with mild population diversification visible in D. grandiflora and particularly in D. ferruginea. This pointed to the highly conserved content and ratio of targeted compounds within the analyzed species, which was not severely influenced by the geographic origin or environmental conditions. The presented metabolomics approach might have, along with morphometrics and molecular genetics studies, a high information value for further elucidation of the relationships among taxa within the genus Digitalis.PMID:36968406 | PMC:PMC10034326 | DOI:10.3389/fpls.2023.1155297