PubMed

Front Mol Biosci. 2022 Oct 17;9:926623. doi: 10.3389/fmolb.2022.926623. eCollection 2022.ABSTRACTMachine learning has become a powerful tool for systems biologists, from diagnosing cancer to optimizing kinetic models and predicting the state, growth dynamics, or type of a cell. Potential predictions from complex biological data sets obtained by "omics" experiments seem endless, but are often not the main objective of biological research. Often we want to understand the molecular mechanisms of a disease to develop new therapies, or we need to justify a crucial decision that is derived from a prediction. In order to gain such knowledge from data, machine learning models need to be extended. A recent trend to achieve this is to design "interpretable" models. However, the notions around interpretability are sometimes ambiguous, and a universal recipe for building well-interpretable models is missing. With this work, we want to familiarize systems biologists with the concept of model interpretability in machine learning. We consider data sets, data preparation, machine learning methods, and software tools relevant to omics research in systems biology. Finally, we try to answer the question: "What is interpretability?" We introduce views from the interpretable machine learning community and propose a scheme for categorizing studies on omics data. We then apply these tools to review and categorize recent studies where predictive machine learning models have been constructed from non-sequential omics data.PMID:36387282 | PMC:PMC9650551 | DOI:10.3389/fmolb.2022.926623

Front Mol Biosci. 2022 Oct 26;9:962431. doi: 10.3389/fmolb.2022.962431. eCollection 2022.ABSTRACTThe increasing availability of multivariate data within biomedical research calls for appropriate statistical methods that can describe and model complex relationships between variables. The extended ANOVA simultaneous component analysis (ASCA+) framework combines general linear models and principal component analysis (PCA) to decompose and visualize the separate effects of experimental factors. It has recently been demonstrated how linear mixed models can be included in the framework to analyze data from longitudinal experimental designs with repeated measurements (RM-ASCA+). The ALASCA package for R makes the ASCA+ framework accessible for general use and includes multiple methods for validation and visualization. The package is especially useful for longitudinal data and the ability to easily adjust for covariates is an important strength. This paper demonstrates how the ALASCA package can be applied to gain insights into multivariate data from interventional as well as observational designs. Publicly available data sets from four studies are used to demonstrate the methods available (proteomics, metabolomics, and transcriptomics).PMID:36387276 | PMC:PMC9645785 | DOI:10.3389/fmolb.2022.962431

Oncoimmunology. 2022 Nov 14;11(1):2146855. doi: 10.1080/2162402X.2022.2146855. eCollection 2022.ABSTRACTWriting in Science, Al Habsi et al. show that spermidine boosts the efficacy of monoclonal antibodies targeting PD-L1 in aged tumor-bearing mice by enhancing fatty acid oxidation in CD8 T cells. These results open new therapeutic avenues to improve the effectiveness of anticancer immunotherapies in aged patients.PMID:36387057 | PMC:PMC9665084 | DOI:10.1080/2162402X.2022.2146855

Front Nutr. 2022 Oct 26;9:998044. doi: 10.3389/fnut.2022.998044. eCollection 2022.ABSTRACTINTRODUCTION AND AIMS: Dietary polyphenols have long been associated with health benefits, including the prevention of obesity and related chronic diseases. Overfeeding was shown to rapidly induce weight gain and fat mass, associated with mild insulin resistance in humans, and thus represents a suitable model of the metabolic complications resulting from obesity. We studied the effects of a polyphenol-rich grape extract supplementation on the plasma metabolome during an overfeeding intervention in adults, in two randomized parallel controlled clinical trials.METHODS: Blood plasma samples from 40 normal weight to overweight male adults, submitted to a 31-day overfeeding (additional 50% of energy requirement by a high calorie-high fructose diet), given either 2 g/day grape polyphenol extract or a placebo at 0, 15, 21, and 31 days were analyzed (Lyon study). Samples from a similarly designed trial on females (20 subjects) were collected in parallel (Lausanne study). Nuclear magnetic resonance (NMR)-based metabolomics was conducted to characterize metabolome changes induced by overfeeding and associated effects from polyphenol supplementation. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov.RESULTS: Changes in plasma levels of many metabolic markers, including branched chain amino acids (BCAA), ketone bodies and glucose in both placebo as well as upon polyphenol intervention were identified in the Lyon study. Polyphenol supplementation counterbalanced levels of BCAA found to be induced by overfeeding. These results were further corroborated in the Lausanne female study.CONCLUSION: Administration of grape polyphenol-rich extract over 1 month period was associated with a protective metabolic effect against overfeeding in adults.PMID:36386937 | PMC:PMC9643885 | DOI:10.3389/fnut.2022.998044

Front Nutr. 2022 Oct 28;9:1044871. doi: 10.3389/fnut.2022.1044871. eCollection 2022.ABSTRACTA wide range of phenolic compounds participate in oilseed growth, regulate oxidative stability of corresponding vegetable oil, and serve as important minor food components with health-promoting effects. Composition distribution of phenolic compounds varied in oilseeds. Isoflavones, sinapic acid derivatives, catechin and epicatechin, phenolic alcohols, chlorogenic acid, and lignans were the main phenolic compounds in soybean, rapeseed, peanut skin, olive, sunflower seed, sesame and flaxseed, respectively. Among which, the total isoflavones content in soybean seeds reached from 1,431 to 2,130 mg/100 g; the main phenolic compound in rapeseed was sinapine, representing 70-90%; chlorogenic acid as the predominant phenolic compound in sunflower kernels, represented around 77% of the total phenolic content. With the rapid development of analytical techniques, it is becoming possible for the comprehensive profiling of these phenolic compounds from oilseeds. This review aims to provide recently developments about the composition distribution of phenolic compounds in common oilseeds, advanced technologies for profiling of phenolic compounds by the metabolomics approaches based on mass spectrometry. As there is still limited research focused on the comprehensive extraction and determination of phenolics with different bound-forms, future efforts should take into account the non-targeted, pseudo-targeted, and spatial metabolomic profiling of phenolic compounds, and the construction of phenolic compound database for identifying and quantifying new types of phenolic compounds in oilseeds and their derived products.PMID:36386934 | PMC:PMC9650096 | DOI:10.3389/fnut.2022.1044871

Front Nutr. 2022 Oct 26;9:1036080. doi: 10.3389/fnut.2022.1036080. eCollection 2022.ABSTRACTNutritional interventions are a promising therapeutic option for addressing obesity and cardiometabolic dysfunction. One such option, intermittent fasting (IF), has emerged as a viable alternative to daily caloric restriction and may beneficially modulate body weight regulation and alter the gut microbiome (GM) and plasma metabolome. This secondary analysis of a larger, registered trial (ClinicalTrials.gov ID: NCT04327141) examined the effect of a four-week intervention comparing one vs. two-consecutive days of IF in combination with protein pacing (IF-P; 4-5 meals/day, >30% protein/day) on the GM, the plasma metabolome, and associated clinical outcomes in overweight and obese adults. Participants (n = 20) were randomly assigned to either a diet consisting of one fasting day (total of 36 h) and six low-calorie P days per week (IF1-P, n = 10) or two fasting days (60 h total) and five low-calorie P days per week (IF2-P, n = 10). The fecal microbiome, clinical outcomes, and plasma metabolome were analyzed at baseline (week 0) and after four weeks. There were no significant time or interaction effects for alpha diversity; however, baseline alpha diversity was negatively correlated with percent body fat change after the four-week intervention (p = 0.030). In addition, beta-diversity for both IF groups was altered significantly by time (p = 0.001), with no significant differences between groups. The IF1-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and Eubacterium fissicatena group (q ≤ 0.007), while the IF2-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and a decrease in Eubacterium ventriosum group (q ≤ 0.005). The plasma metabolite profile of IF2-P participants displayed significant increases in serine, trimethylamine oxide (TMAO), levulinic acid, 3-aminobutyric acid, citrate, isocitrate, and glucuronic acid (q ≤ 0.049) compared to IF1-P. Fecal short-chain fatty acid concentrations did not differ significantly by time or between groups (p ≥ 0.126). Interestingly, gastrointestinal symptoms were significantly reduced for the IF2-P group but not for the IF1-P group. Our results demonstrate that short-term IF modestly influenced the GM community structure and the plasma metabolome, suggesting these protocols could be viable for certain nutritional intervention strategies.PMID:36386914 | PMC:PMC9644216 | DOI:10.3389/fnut.2022.1036080

Front Microbiol. 2022 Oct 28;13:935884. doi: 10.3389/fmicb.2022.935884. eCollection 2022.ABSTRACTMicroorganisms play a key role in ruminal digestion, some of which can be used as probiotics to promote growth in ruminants. However, which potential bacteria are responsible for ruminant growth and how they potentiate the basic mechanism is unclear. In this study, three bacterial strains, Bacillus pumilus (SN-3), Bacillus paralicheniformis (SN-6), and Bacillus altitudinis (SN-20) with multiple digestive enzymes were isolated from the rumen of healthy buffaloes. Among these strains, SN-6 secreted cellulase, laccase, and amylase, and significantly inhibited Staphylococcus aureus ATCC25923 and Escherichia coli K99 in vitro. In addition, SN-6 exhibited strong tolerance to artificial gastric juice, intestinal juice, and high temperature. Antibiotic resistance test, virulence gene test, and mouse toxicity test confirmed the safety of SN-6. Further, SN-6 significantly increased the body weight (p < 0.01), affects the intestinal microbiota structure, and alters the metabolomic patterns of Simmental. There was a remarkable difference in the β diversity of fecal microflora between SN-6 and control groups (p < 0.05). Furthermore, SN-6 significantly increased the abundance of Clostridium_sensu_stricto_1, Bifidobacterium, Blautia, and Cellulolyticum, decreased the relative abundance of Monoglobus and norank_f_Ruminococcacea. Moreover, SN-6 feeding significantly enriched intestinal metabolites (i.e., 3-indoleacrylic acid, kynurenic acid) to maintain intestinal homeostasis. Finally, the microbial and metabolic functional analysis indicated that SN-6 could enhance amino acid metabolism (mainly tryptophan metabolism) and lipid metabolism pathways. Overall, these findings indicated that SN-6 could be used as a probiotic in ruminants.PMID:36386716 | PMC:PMC9649902 | DOI:10.3389/fmicb.2022.935884

Front Microbiol. 2022 Oct 25;13:981994. doi: 10.3389/fmicb.2022.981994. eCollection 2022.ABSTRACTUltra-high performance liquid chromatography-high-resolution mass spectrometry (UPHLC-HRMS) is used to discover and monitor single or sets of biomarkers informing about metabolic processes of interest. The technique can detect 1000's of molecules (i.e., metabolites) in a single instrument run and provide a measurement of the global metabolome, which could be a fingerprint of activity. Despite the power of this approach, technical challenges have hindered the effective use of metabolomics to interrogate microbial communities implicated in the removal of priority contaminants. Herein, our efforts to circumvent these challenges and apply this emerging systems biology technique to microbiomes relevant for contaminant biodegradation will be discussed. Chlorinated ethenes impact many contaminated sites, and detoxification can be achieved by organohalide-respiring bacteria, a process currently assessed by quantitative gene-centric tools (e.g., quantitative PCR). This laboratory study monitored the metabolome of the SDC-9™ bioaugmentation consortium during cis-1,2-dichloroethene (cDCE) conversion to vinyl chloride (VC) and nontoxic ethene. Untargeted metabolomics using an UHPLC-Orbitrap mass spectrometer and performed on SDC-9™ cultures at different stages of the reductive dechlorination process detected ~10,000 spectral features per sample arising from water-soluble molecules with both known and unknown structures. Multivariate statistical techniques including partial least squares-discriminate analysis (PLSDA) identified patterns of measurable spectral features (peak patterns) that correlated with dechlorination (in)activity, and ANOVA analyses identified 18 potential biomarkers for this process. Statistical clustering of samples with these 18 features identified dechlorination activity more reliably than clustering of samples based only on chlorinated ethene concentration and Dhc 16S rRNA gene abundance data, highlighting the potential value of metabolomic workflows as an innovative site assessment and bioremediation monitoring tool.PMID:36386687 | PMC:PMC9641191 | DOI:10.3389/fmicb.2022.981994

Front Pharmacol. 2022 Oct 31;13:966218. doi: 10.3389/fphar.2022.966218. eCollection 2022.ABSTRACTAnxiety disorder is one of the most common mental diseases. It is mainly characterized by a sudden, recurring but indescribable panic, fear, tension and/or anxiety. Yangshendingzhi granules (YSDZ) are widely used in the treatment of anxiety disorders, but its active ingredients and underlying mechanisms are not yet clear. This study integrates network pharmacology and metabolomics to investigate the potential mechanism of action of YSDZ in a rat model of anxiety. First, potential active ingredients and targets were screened by network pharmacology. Then, predictions were verified by molecular docking, molecular dynamics and western blotting. Metabolomics was used to identify differential metabolites and metabolic pathways. All results were integrated for a comprehensive analysis. Network pharmacology analysis found that Carotene, β-sitosterol, quercetin, Stigmasterol, and kaempferol in YSDZ exert anxiolytic effects mainly by acting on IL1β, GABRA1, PTGS1, ESR1, and TNF targets. Molecular docking results showed that all the affinities were lower than -5 kcal/mol, and the average affinities were -7.7764 kcal/mol. Molecular dynamics simulation results showed that RMSD was lower than 2.5 A, and the overall conformational changes of proteins were small, indicating that the small molecules formed stable complexes with proteins. The results of animal experiments showed that YSDZ exerts anxiolytic effects by regulating GABRA1 and TNF-α, ameliorating pathological damage in hippocampal CA1, and regulating metabolic pathways such as thiamine, cysteine and methionine metabolism, lysine biosynthesis and degradation. Altogether, we reveal multiple mechanisms through which YSDZ exerts its anti-anxiety effects, which may provide a reference for its clinical application and drug development.PMID:36386232 | PMC:PMC9659911 | DOI:10.3389/fphar.2022.966218

Front Pharmacol. 2022 Oct 26;13:1012063. doi: 10.3389/fphar.2022.1012063. eCollection 2022.ABSTRACTLung cancer is one of the malignant tumors with the fastest incidence rate and mortality growth and the greatest threat to human health and life. Marsdenia tenacissima is an antitumor of Chinese medicine. However, Marsdenia tenacissima has low bioavailability in the human body and most of its main active substances are aglycones, such as Tenacigenin A, Tenacigenin B. This study aims to produce biotransformation products rich in pungent saponins by using Marsdenia tenacissima as a fermentation medium of Ganoderma lucidum. Non-targeted metabolomics analysis was carried out on the fermentation products after the optimization process. A total of 249 differential metabolites were detected, and the content of saponins increased from 0.1% to 0.41% and most of them were tenacigenin. Furthermore, the biotransformation of C21 steroidal glycosides in Marsdenia tenacissima was the central reaction in this fermentation process. Pharmacodynamics resewed that the anticancer effect of Marsdenia tenacissima was significantly enhanced after fermentation, mainly through inhibiting the growth and apoptosis of cancer cells.PMID:36386222 | PMC:PMC9643841 | DOI:10.3389/fphar.2022.1012063

Front Pharmacol. 2022 Nov 1;13:1037563. doi: 10.3389/fphar.2022.1037563. eCollection 2022.ABSTRACTAmygdalus mongolica oil is rich in unsaturated fatty acids such as inoleic acid (47.11%) and oleic acid (23.81%). Our research demonstrates that it exerts a protective effect on rat models of pulmonary fibrosis, however, little is known regarding the underlying mechanism of action. This study aimed to characterize the therapeutic mechanism of action of A. mongolica oil on bleomycin-induced pulmonary fibrosis in rats. A. mongolica oil appears to regulate the levels of potential key serum biomarkers which include tetrahydrobiopterin, L-serine, citrulline and estradiol to participate in folate biosynthesis, glycine, serine and threonine metabolism, arginine biosynthesis and steroid hormone biosynthesis. And it also enriched intestinal microbial abundance, homogeneity and modulated the abundance of Duncaniell, Desulfovibrio, Peptococcaceae_unclassified, Dubosiella, Tyzzerella, Lachnospiraceae_NK4A136_group, Lactobacillus, Clostridiales_unclassified to exert a protective effect against pulmonary fibrosis. A. mongolica oil appears to confer protective effects against pulmonary fibrosis by affecting the level of pulmonary fibrosis metabolites and the abundance of related intestinal flora through multiple targets, as evidenced by our untargeted LC-MS/MS metabonomics evaluation and 16S rDNA sequencing technology.PMID:36386194 | PMC:PMC9663812 | DOI:10.3389/fphar.2022.1037563

Front Pharmacol. 2022 Oct 28;13:1066875. doi: 10.3389/fphar.2022.1066875. eCollection 2022.NO ABSTRACTPMID:36386182 | PMC:PMC9650449 | DOI:10.3389/fphar.2022.1066875

Front Pharmacol. 2022 Oct 24;13:1044808. doi: 10.3389/fphar.2022.1044808. eCollection 2022.ABSTRACTBackground: Anti-tuberculosis drug-induced liver injury (ATB-DILI) is an adverse reaction with a high incidence and the greatest impact on tuberculosis treatment. However, there is a lack of effective biomarkers for the early prediction of ATB-DILI. Herein, this study uses UPLC‒MS/MS to reveal the plasma metabolic profile and lipid profile of ATB-DILI patients before drug administration and screen new biomarkers for predicting ATB-DILI. Methods: A total of 60 TB patients were enrolled, and plasma was collected before antituberculosis drug administration. The untargeted metabolomics and lipidomics analyses were performed using UPLC‒MS/MS, and the high-resolution mass spectrometer Q Exactive was used for data acquisition in both positive and negative ion modes. The random forest package of R software was used for data screening and model building. Results: A total of 60 TB patients, including 30 ATB-DILI patients and 30 non-ATB-DILI subjects, were enrolled. There were no significant differences between the ATB-DILI and control groups in age, sex, smoking, drinking or body mass index (p > 0.05). Twenty-two differential metabolites were selected. According to KEGG pathway analysis, 9 significantly enriched metabolic pathways were found, and both drug metabolism-other enzymes and niacin and nicotinamide metabolic pathways were found in both positive and negative ion models. A total of 7 differential lipid molecules were identified between the two groups. Ferroptosis and biosynthesis of unsaturated fatty acids were involved in the occurrence of ATB-DILI. Random forest analysis showed that the model built with the top 30 important variables had an area under the ROC curve of 0.79 (0.65-0.93) for the training set and 0.79 (0.55-1.00) for the validation set. Conclusion: This study demonstrated that potential markers for the early prediction of ATB-DILI can be found through plasma metabolomics and lipidomics. The random forest model showed good clinical predictive value for ATB-DILI.PMID:36386176 | PMC:PMC9641415 | DOI:10.3389/fphar.2022.1044808

Front Pharmacol. 2022 Oct 31;13:1027931. doi: 10.3389/fphar.2022.1027931. eCollection 2022.ABSTRACTViscum album is a semi-parasitic plant used for over one hundred years in complementary cancer therapy. The main commercial drugs used in cancer patients' treatment are derived from the aqueous V. album extracts, whose cytotoxic potential is mostly attributed to the aqueous soluble antitumoral metabolites. On the counterpart, ethanol solvents must be used to obtain V. album mother tinctures. This methodology permits better solubilization of phenolic compounds, among others, which present antitumoral bioactivity. Recently, the metabolomics approach revealed the influence of the host tree on the V. album subspecies differentiation. To increase the scientific information about the chemical differences related to the host trees and to clarify the seasonal influences, in this study, the metabolome of 50 V. album mother tinctures from three subspecies (abietis, album, austriacum) and five host trees (Malus domestica, Quercus sp., Ulmus carpinifolia, Pinus sylvestris, Abies alba) was evaluated using summer and winter plant harvests. The in vitro cytotoxic activities were investigated in breast cancer cells (MDA-MB-231) and immortalized normal human keratinocytes (HaCaT). The summer V. album mother tinctures presented higher cytotoxic activity than winter ones. Among the summer samples, those prepared with V. album subsp. album were more cytotoxic than V. album subsp. abietis and subsp. V. album subsp. austriacum. The V. album harvested from Quercus petraea and Abies alba inhibited the key-glycolytic enzymes: hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK). This activity was related to a reduction in glucose uptake and lactate production, which were host-tree-time-dose-dependent. The untargeted metabolomic approach was able to discriminate the mother tinctures according to respective botanical classes and harvest season. A total of 188 metabolites were annotated under positive and negative modes. Fourteen compounds were responsible for the samples differentiation, and, to the best of our knowledge, eight were described in the Viscum album species for the first time. Our study shows the interruption of the Warburg effect as a novel antitumoral mechanism triggered by V. album mother tinctures, which is related to their metabolite profile. These results bring scientific evidence that encourages the use of V. album mother tinctures as a natural product for cancer therapy.PMID:36386174 | PMC:PMC9662615 | DOI:10.3389/fphar.2022.1027931

Front Pharmacol. 2022 Oct 31;13:1045843. doi: 10.3389/fphar.2022.1045843. eCollection 2022.ABSTRACTInter- and intrapatient variability of tacrolimus exposure is a vital prognostic risk factor for the clinical outcome of liver transplantation. New factors or biomarkers characterizing tacrolimus disposition is essential for optimal dose prediction in recipients of liver transplant. The aim of the study was to identify potential plasma metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients by using a global metabolomic approach. A total of 693 plasma samples were collected from 137 liver transplant recipients receiving tacrolimus and regular therapeutic drug monitoring. Untargeted metabolomic analysis was performed by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. Univariate and multivariate analyses with a mixed linear model were conducted, and the results showed that the dose-adjusted tacrolimus trough concentration was associated with 31 endogenous metabolites, including medium- and long-chain acylcarnitines such as stearoylcarnitine (β = 0.222, p = 0.001), microbiota-derived uremic retention solutes such as indolelactic acid (β = 0.194, p = 0.007), bile acids such as taurohyodeoxycholic acid (β = -0.056, p = 0.002), and steroid hormones such as testosterone (β = 0.099, p = 0.001). A multiple linear mixed model including 11 metabolites and clinical information was established with a suitable predictive performance (correlation coefficient based on fixed effects = 0.64 and correlation coefficient based on fixed and random effects = 0.78). These data demonstrated that microbiota-derived uremic retention solutes, bile acids, steroid hormones, and medium- and long-chain acylcarnitines were the main metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients.PMID:36386159 | PMC:PMC9659571 | DOI:10.3389/fphar.2022.1045843

Front Pharmacol. 2022 Oct 26;13:1056614. doi: 10.3389/fphar.2022.1056614. eCollection 2022.ABSTRACTBackground: Adult neurogenesis plays an important role in repairing damaged neurons and improving cognitive impairment in Alzheimer's disease (AD). B. Papyrifera (L.) L'Hér. ex Vent. fruits (BL), a traditional Chinese medicine for tonifying the kidney, has been reported to improve cognitive function in AD mice, but the underlying mechanisms have not been clearly illuminated. This study aimed to provide an overview of the differential compounds in the brain of APP/PS1 mice after BL water extract (BLWE) treatment through metabolomics technology and to elucidate whether the therapeutic effect and mechanism are through the enhancement of neurogenesis. Methods: APP/PS1 transgenic mice were treated with different doses of BLWE. After 6 weeks of intragastric injection, the therapeutic effects of BLWE on APP/PS1 transgenic mice were determined by the Morris water maze test, immunohistochemistry, hematoxylin & eosin and Nissl staining, enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Subsequently, metabolomics technology was used to analyze the regulatory effect of BLWE on differential compounds in the brain of APP/PS1 mice, and on this basis, its molecular mechanism of BLWE was screened. Finally, the protein expression of the Wnt/β-catenin signaling pathway was detected by Western blotting. Results: After BLWE treatment, the learning and memory function of APP/PS1 mice were significantly improved, which was related to the increase in the number of Nestin+/BrdU+ and NeuN+/BrdU+ cells, and the decrease in the number of apoptotic cells in the hippocampus. BLWE treatment could also up-regulate the expression of synapse-associated proteins. Moreover, BLWE could modulate endogenous metabolic compounds in the brains of AD mice, including N-acetyl-aspartate, glutamine, etc. Furthermore, BLWE inhibited the phosphorylation of Tyr216-GSK-3β and β-catenin protein while increased CyclinD1 protein expression. Conclusion: We demonstrated that BLWE can enhance neural stem cells proliferation and improve neurogenesis, thereby efficiently repairing damaged neurons in the hippocampus and ameliorating cognitive impairment in APP/PS1 transgenic mice. The mechanism is at least partly through activating the Wnt/β-catenin signaling pathway.PMID:36386124 | PMC:PMC9643563 | DOI:10.3389/fphar.2022.1056614

J Anal Methods Chem. 2022 Nov 4;2022:8026410. doi: 10.1155/2022/8026410. eCollection 2022.ABSTRACTDendrobium officinale (D. officinale) is a valuable traditional Chinese herbal medicine with high commercial value. In Chinese Pharmacopoeia (Ch.P., 2020 edition), the quality of D. officinale is mainly evaluated by its polysaccharide content. However, varying growth and production conditions, such as cultivation environment, origin, harvesting process, or processing methods, resulting in highly variable yields, quality, and composition. The aim of this study was to investigate whether the content of secondary metabolites in D. officinale from different origins is consistent with the polysaccharide content. The results showed that the polysaccharide content and pass rate were ranked as GX > AH > GZ > YN. Based on the nontargeted metabolomics approach, we searched for differential components in 22 different regions of D. officinale, including amides, bibenzyls, disaccharide, flavonoids, organic nitrogenous compounds, and phenolic glycosides. The overall expression was opposite to the polysaccharide, and the most expressed was YN, followed by GZ, AH, and GX. These results indicated that the current quality standard for evaluating the quality of D. officinale by polysaccharide content alone is imperfect, and small molecule compounds need to be included as quality markers.PMID:36385774 | PMC:PMC9652072 | DOI:10.1155/2022/8026410

Plant Biol (Stuttg). 2022 Nov 17. doi: 10.1111/plb.13489. Online ahead of print.ABSTRACTLow temperature limits the geographical distribution and yield of plants. Hormones play an important role in coordinating the growth and development of plants and their tolerance to low temperature. However, the mechanisms by which hormones affect plant resistance to extreme cold stress in the natural environment are still unclear. In this study, two winter wheat varieties with different cold resistances, Dn1 and J22, were used to conduct targeted plant hormone metabolome analysis on the tillering nodes of winter wheat at 5 °C, -10 °C and -25 °C using an LC-ESI-MS/MS system. We screened 39 hormones from 88 plant hormone metabolites and constructed a partial regulatory network of auxin, jasmonic acid and cytokinin. GO analysis and enrichment of KEGG pathways in differential metabolites showed that the "plant hormone signal transduction" pathway was the most typical. Our study showed that extreme low temperature increased the levels of most auxin, cytokinin and salicylic acid, and decreased the levels of jasmonic acid and abscisic acid, and the levels of auxin, jasmonic acid and cytokinin in Dn1 were greater than those in J22. These changes in hormone levels were associated with changes in gene expression in synthesis, catabolism, transport and signal transduction pathways. These results seem to be different from the previous hormone regulation mechanisms obtained mostly at 4 °C. Our results provide a basis for further understanding the molecular mechanisms by which plant endogenous hormones regulate plant freeze stress tolerance.PMID:36385725 | DOI:10.1111/plb.13489

J Sep Sci. 2022 Nov 17. doi: 10.1002/jssc.202200705. Online ahead of print.ABSTRACTMakyo-kanseki-to has been used for the treatment of pneumonia, becoming a basic formula for COVID-19. However, the chemical profile of Makyo-kanseki-to granule and its possible mechanism against acute lung injury from terminal metabolic regulation have been unclear. The aim of this study was to characterize the constituents in Makyo-kanseki-to granule and reveal the potential related mechanism of Makyo-kanseki-to granule treatment for acute lung injury using a rat model of lipopolysaccharide induced acute lung injury. Totally, 78 constituents were characterized based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Makyo-kanseki-to granule could alleviate acute lung injury through modulating rectal temperature, pulmonary edema, histopathology, processes of inflammatory and oxidative stress. 22 potential biomarkers in acute lung injury rats were identified by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole exactive high field mass spectrometry. They were mainly involved in amino acids and glycerophospholipid metabolism, which were regulated by Makyo-kanseki-to granule. The present results not only increase the understanding on the chemical profile and molecular mechanism of Makyo-kanseki-to granule mediated protection against acute lung injury, but also provide experimental basis and new ideas for further development and clinical application of Makyo-kanseki-to granule. This article is protected by copyright. All rights reserved.PMID:36385590 | DOI:10.1002/jssc.202200705

Appl Microbiol Biotechnol. 2022 Nov 17. doi: 10.1007/s00253-022-12265-7. Online ahead of print.ABSTRACTAtherosclerosis (AS) is a major cause of death and morbidity worldwide. There is an increasing amount of evidence that the gut microbiota plays an important role in disorders associated with lipid metabolism, such as AS, and alterations in the composition of the gut microbiota and its metabolic potential have been identified as contributing factors in the development of AS. Recently, probiotics have attracted great interest for their excellent cholesterol-lowering ability, their capacity to improve vascular endothelial function, and their participation in the remodeling of the intestinal flora to prevent AS. The incidental findings of our other study suggest that probiotic Lactobacillus rhamnosus GG may be associated with slowing the progression of AS. Thus, we delivered strain GG into mice by oral feeding and found that strain GG could effectively inhibit AS plaque generation. We analyzed the differences in gut microbiota composition and the peripheral blood metabolome in mice after oral feeding of strain GG by 16S DNA sequencing and untargeted metabolomics, respectively. The results showed that strain GG changed the composition of the gut microbiota in mice fed a high-fat diet; elevated the abundance of beneficial bacteria, such as Bilophila and Alistipes, and decreased the abundance of harmful bacteria, such as Deltaproteobacteria. The results of enrichment analysis of the gut microbiota and the peripheral blood metabolome both indicated that the antiatherosclerotic effect of strain GG might be associated with the biosynthesis pathway of ketone bodies. In addition, strain GG attenuated endothelial injury and elevated peripheral blood ketone body content in mice but did not significantly affect low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) content. In conclusion, our study provides new evidence that strain GG slows the progression of AS, which may be associated with its improvement of the gut microbiome and peripheral blood metabolome, its ability to increase the abundance of beneficial bacteria, and its participation in unsaturated fatty acid and ketone body synthesis and degradation. KEY POINTS: • L. rhamnosus GG attenuated endothelial injury and atherosclerotic plaque formation • L. rhamnosus GG elevated the abundance of beneficial bacteria • L. rhamnosus GG elevated peripheral blood ketone body content in mice.PMID:36385568 | DOI:10.1007/s00253-022-12265-7