PubMed

Curr Osteoporos Rep. 2023 Apr 15. doi: 10.1007/s11914-023-00785-8. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: To systematically review recent studies investigating the association between metabolites and bone mineral density (BMD) in humans.METHODS: Using predefined keywords, we searched literature published from Jan 1, 2019 to Feb 20, 2022 in PubMed, Web of Science, Embase, and Scopus. Studies that met the predefined exclusion criteria were excluded. Among the included studies, we identified metabolites that were reported to be associated with BMD by at least three independent studies.RECENT FINDINGS: A total of 170 studies were retrieved from the databases. After excluding studies that did not meet our predefined inclusion criteria, 16 articles were used in this review. More than 400 unique metabolites in blood were shown to be significantly associated with BMD. Of these, three metabolites were reported by ≥ 3 studies, namely valine, leucine and glycine. Glycine was consistently shown to be inversely associated with BMD, while valine was consistently observed to be positively associated with BMD. Inconsistent associations with BMD was observed for leucine. With advances in metabolomics technology, an increasing number of metabolites associated with BMD have been identified. Two of these metabolites, namely valine and glycine, were consistently associated with BMD, highlighting their potential for clinical application in osteoporosis. International collaboration with a larger population to conduct clinical studies on these metabolites is warranted. On the other hand, given that metabolomics could be affected by genetics and environmental factors, whether the inconsistent association of the metabolites with BMD is due to the interaction between metabolites and genes and/or lifestyle warrants further study.PMID:37060383 | DOI:10.1007/s11914-023-00785-8

Food Funct. 2023 Apr 14. doi: 10.1039/d3fo01044a. Online ahead of print.ABSTRACTThis study investigated the effects of dietary berberine (BBR) supplementation on the growth performance, intestinal health, and ileal microbiome and metabolomic profile in weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC). Dietary BBR supplementation significantly attenuated the reduced average daily gain (ADG) and attenuated the increased feed to gain ratio (F/G) and the incidence of diarrhea induced by ETEC K88 (P < 0.05). Dietary BBR supplementation significantly increased the villus height and the villus height to crypt depth ratio in the ileum (P < 0.05). Moreover, the mRNA expression of ZO-1 and occludin as well as aquaporins (AQP1, AQP3, AQP4, AQP7, and AQP10) and Na+/H+ exchanger 3 (NHE3) in ileal mucosa was significantly upregulated by BBR treatment (P < 0.05). Additionally, BBR treatment significantly inhibited the increase of interleukin-1β (IL-1β) in jejunal mucosa caused by ETEC and reduced the levels of tumor necrosis factor-α (TNF-α) and IL-1β and increased interleukin-10 (IL-10) in colonic mucosa (P < 0.05). Dietary BBR treatment significantly increased the Observed_species, Chao 1, abundance based coverage estimators (ACE), and PD_whole tree in the ileal digesta of weaned piglets challenged with ETEC. At the genus level, the relative abundance of unidentified Clostridiales was decreased, while Weissella, Alloprevotella, unidentified Prevotellaceae, and Catenibacterium were increased in the BBR + ETEC group when compared to the ETEC group (P < 0.05). Spearman correlation analysis showed that the relative abundance of unidentified Clostridiales (genus) was negatively correlated with the ileal villus height but negatively correlated with diarrhea and intestinal IL-1β and TNF-α concentrations (P < 0.05). The ileal metabolome analysis showed that the metabolic pathways including primary and secondary bile acid biosynthesis and bile secretion were significantly enriched by BBR treatment. Collectively, dietary BBR supplementation effectively improved the growth performance and alleviated the diarrhea and intestinal injury induced by ETEC K88 in weaned piglets, which might closely involve the modulation of ileal microbiota and metabolites.PMID:37060117 | DOI:10.1039/d3fo01044a

Plant Physiol Biochem. 2023 Apr 14;199:107709. doi: 10.1016/j.plaphy.2023.107709. Online ahead of print.ABSTRACTAnthocyanins can be induced by environmental factors such as low-temperature and play essential roles in plant color formation. In this study, leaves of Aesculus chinensis Bunge var. chinensis with different colors under natural low-temperature in autumn were collected and grouped into green leaf (GL) and red leaf (RL). To reveal the underlying mechanism of color formation in RL, a combined analysis of the metabolome and transcriptome was conducted with GL and RL. Metabolic analyses revealed that total anthocyanin content and primary anthocyanin components were increased RL relative to GL and cyanidin was the main anthocyanin compound in RL. Transcriptome analysis provided a total of 18720 differentially expressed genes (DEGs), of which 9150 DEGs were upregulated and 9570 DEGs were downregulated in RL relative to GL. KEGG analysis showed that DEGs were mainly enriched in flavonoid biosynthesis, phenylalanine metabolism, and phenylpropanoid biosynthesis. Furthermore, co-expression network analysis indicated that 56 AcMYB transcription factors were highly expressed in RL compared with GL, among which AcMYB113 (an R2R3-MYB TF) had a strong correlation with anthocyanins. Overexpression of AcMYB113 in apple resulted in dark-purple transgenic calluses. In addition, the transient expression experiment showed that AcMYB113 enhanced anthocyanin synthesis by activating pathways of anthocyanin biosynthesis in leaves of Aesculus chinensis Bunge var. chinensis. Taken together, our findings reveal new insights into the molecular mechanism of anthocyanin accumulation in RL and provide candidate genes for the breeding of anthocyanin-rich cultivars.PMID:37094493 | DOI:10.1016/j.plaphy.2023.107709

Biochem Biophys Res Commun. 2023 Apr 14;661:42-49. doi: 10.1016/j.bbrc.2023.04.032. Online ahead of print.ABSTRACTMembrane transport proteins are essential for the transport of a wide variety of molecules across the cell membrane to maintain cellular homeostasis. Generally, these transport proteins can be overexpressed in a suitable host (bacteria, yeast, or mammalian cells), and it is well documented that overexpression of membrane proteins alters the global metabolomic and proteomic profiles of the host cells. In the present study, we investigated the physiological consequences of overexpression of a membrane transport protein YdgR that belongs to the POT/PTR family from E. coli by using the lab strain BL21 (DE3)pLysS in its functional and attenuated mutant YdgR-E33Q. We found significant differences between the omics (metabolomics and proteomics) profiles of the cells expressing functional YdgR as compared to cells expressing attenuated YdgR, e.g., upregulation of several uncharacterized y-proteins and enzymes involved in the metabolism of peptides and amino acids. Furthermore, molecular network analysis suggested a relatively higher presence of proline-containing tripeptides in cells expressing functional YdgR. We envisage that an in-depth investigation of physiological alterations due to protein over-expression may be used for the deorphanization of the y-gene transportome.PMID:37087797 | DOI:10.1016/j.bbrc.2023.04.032

J Chromatogr A. 2023 Apr 14;1697:463994. doi: 10.1016/j.chroma.2023.463994. Online ahead of print.ABSTRACTMonitoring the central carbon metabolism (CCM) network using liquid chromatography/mass spectrometry (LC-MS) analysis is hampered by the diverse chemical nature of its analytes, which are extremely difficult to analyze using single chromatographic conditions. Furthermore, CCM-related compounds present non-specific adsorption on metal surfaces, causing detrimental chromatographic effects and sensitivity loss. In this study, polar reversed-phase, mixed-mode (MMC), and zwitterionic hydrophilic interaction chromatography (HILIC) featuring low-adsorption hardware were investigated towards untargeted analysis of biological samples with a focus on energy metabolism-related analytes. Best results were achieved with sulfoalkylbetaine HILIC with different supports, where polymeric option featured the highest coverage and inert hybrid silica facilitated best throughput and kinetic performance at a cost of less selectivity for small carboxylic acids. MMC demonstrated excellent performance for strongly anionic analytes such as multiresidue phosphates. The obtained experimental data also suggested that an additional hydrophilic modulation might be necessary to facilitate better resolution of carboxylic acids in zHILIC mode, as found during the application of the developed method to study the effect of two different mutations on the energy metabolism of S. aureus.PMID:37086708 | DOI:10.1016/j.chroma.2023.463994

Redox Biol. 2023 Apr 14;62:102699. doi: 10.1016/j.redox.2023.102699. Online ahead of print.ABSTRACTAberrant tumor metabolism is a hallmark of cancer in which metabolic rewiring can support tumor growth under nutrient deficient conditions. KRAS mutations occur in 35-45% of all colorectal cancer (CRC) cases and are difficult to treat. The relationship between mutant KRAS and aberrant metabolism in CRCs has not been fully explored and could be a target for intervention. We previously acquired non-targeted metabolomics data from 161 tumor tissues and 39 normal colon tissues from stage I-III chemotherapy naïve CRC patients. In this study, we revealed that only in male patients, tumors with KRAS mutations had several altered pathways that suppress ferroptosis, including glutathione biosynthesis, transsulfuration activity, and methionine metabolism. To validate this phenotype, MC38 CRC cells (KRASG13R) were treated with a ferroptosis inducer; RAS-selected lethal (RSL3). RSL3 altered metabolic pathways in the opposite direction to that seen in KRAS mutant tumors from male patients confirming a suppressed ferroptosis metabolic phenotype in these patients. We further validated gene expression data from an additional CRC patient cohort (Gene Expression Omnibus (GEO)), and similarly observed differences in ferroptosis-related genes by sex and KRAS status. Further examination of the relationship between these genes and overall survival (OS) in the GEO cohort showed that KRAS mutant tumors are associated with poorer 5-year OS compared to KRAS wild type tumors, and only in male patients. Additionally, high compared to low expression of GPX4, FTH1, FTL, which suppress ferroptosis, were associated with poorer 5-year OS only in KRAS mutant tumors from male CRC patients. Additionally, low compared to high expression of ACSL4 was associated with poorer OS for this group. Our results show that KRAS mutant tumors from male CRC patients have suppressed ferroptosis, and gene expression changes that suppress ferroptosis associate with adverse outcomes for these patients, revealing a novel potential avenue for therapeutic approaches.PMID:37086630 | DOI:10.1016/j.redox.2023.102699

J Pharm Biomed Anal. 2023 Apr 14;230:115399. doi: 10.1016/j.jpba.2023.115399. Online ahead of print.ABSTRACTThe present work focuses on the phytochemical characterization and evaluation of antianginal activity of the bark of Sterculia setigera. It was collected and authenticated in the African region of Mali, where the local population largely employs this plant for the treatment of several diseases. In the context of traditional or folk medicine and recent progresses in alternative medicine practices, it is essential to expand the knowledge about the chemical composition of such medicinal plants. In this research, a direct-Mass Spectrometry (MS) technique, known as Rapid Evaporative Ionization Mass Spectrometry (REIMS) was used for the identification of the main constituents of the Sterculia setigera bark. The REIMS source is here coupled with an electroknife as sampling device, so that the dried and pulverized bark was directly cut through the electroknife to generate a vapor, which was online transferred to the source via a Venture tube. In this way, an ambient MS approach was realized, which avoids any sample preparation procedure or pretreatment; the sample was analyzed in its native state according to a time-saving analytical process. A quadrupole-time of flight MS/MS analyzer was exploited for the identification process, based on mass accuracy data and MS/MS experiments for structure elucidation purposes. Lipids, including triterpenes, fatty acids, γ-sitosterol and α-tocopherol, and phenolic compounds were identified, some of them reported for the first time in a plant of the Sterculia genus and further confirmed through a gas chromatography-mass spectrometry analysis. The obtained metabolomic profile was successfully correlated to the antianginal activity of this plant.PMID:37084664 | DOI:10.1016/j.jpba.2023.115399

Int J Food Microbiol. 2023 Apr 14;397:110212. doi: 10.1016/j.ijfoodmicro.2023.110212. Online ahead of print.ABSTRACTThe quality and composition of strong-flavor Baijiu (SFB), a type of Chinese liquor, depends on the variety of sorghum used in fermentation. However, comprehensive in situ studies measuring the effects sorghum varieties on the fermentation are lacking and the underlying microbial mechanisms remains poorly understood. We studied the in situ fermentation of SFB by using metagenomic, metaproteomic, and metabolomic techniques across four sorghum varieties. Sensory characteristics were best for SFB made from glutinous variety Luzhouhong, followed by glutinous hybrid Jinnuoliang and Jinuoliang, and those made with non-glutinous Dongzajiao. In agreement with sensory evaluations, the volatile composition of SFB samples differed between sorghum varieties (P < 0.05). Fermentation of different sorghum varieties varied in microbial diversity, structure, volatile compounds, and physicochemical properties (pH, temperature, starch, reducing sugar, and moisture) (P < 0.05), with most changes occurring within the first 21 days. Additionally, the microbial interactions and their relationship with volatiles, as well as the physicochemical factors that govern microbial succession, differed between varieties of sorghum. The number of physicochemical factors affecting bacterial communities outweighed those affecting fungal communities, suggesting that bacteria were less resilient to the brewing conditions. This correlates with the finding that bacteria play a major role in the differences in microbial communities and metabolic functions during fermentation with the different varieties of sorghum. Metagenomic function analysis revealed differences in amino acid and carbohydrate metabolism between sorghum varieties throughout most of the brewing process. Metaproteomics further indicated most differential proteins were found in these two pathways, related to differences in volatiles between sorghum varieties of Baijiu and originating from Lactobacillus. These results provide insight into the microbial principles underlying Baijiu production and can be used to improve the quality of Baijiu by selecting the appropriate raw materials and optimizing fermentation parameters.PMID:37084618 | DOI:10.1016/j.ijfoodmicro.2023.110212

J Hazard Mater. 2023 Apr 14;453:131421. doi: 10.1016/j.jhazmat.2023.131421. Online ahead of print.ABSTRACTAtmospheric deposition is an essential cadmium (Cd) pollution source in agricultural ecosystems, entering crops via roots and leaves. In this study, atmospherically deposited Cd was simulated using cadmium sulfide nanoparticles (CdSN), and chili (Capsicum frutescens L.) was used to conduct a comparative foliar and root experiment. Root and foliar uptake significantly increased the Cd content of chili tissues as well as the subcellular Cd content. Scanning electron microscopy and high-resolution secondary ion mass spectrometry showed that Cd that entered the leaves via stomata was fixed in leaf cells, and the rest was mainly through phloem transport to the other organs. In leaf, stem, and root cell walls, Cd signal intensities were 47.4%, 72.2%, and 90.0%, respectively. Foliar Cd uptake significantly downregulated purine metabolism in leaves, whereas root Cd uptake inhibited stilbenoid, diarylheptanoid, and gingerol biosynthesis in roots. Root uptake contributed 90.4% Cd in fruits under simultaneous root and foliar uptake conditions attributed to xylem and phloem involvement in Cd translocation. Moreover, root uptake had a more significant effect on fruit metabolic pathways than foliar uptake. These findings are critical for choosing pollution control technologies and ensuring food security.PMID:37080031 | DOI:10.1016/j.jhazmat.2023.131421

J Plant Res. 2023 Apr 15. doi: 10.1007/s10265-023-01458-4. Online ahead of print.NO ABSTRACTPMID:37059939 | DOI:10.1007/s10265-023-01458-4

J Pharm Biomed Anal. 2023 Apr 11;230:115392. doi: 10.1016/j.jpba.2023.115392. Online ahead of print.ABSTRACTMinimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE), with high incidence and a high rate of clinically missed diagnosis. Early diagnosis of MHE and effective clinical intervention are of great importance. Rhubarb decoction (RD)-induced retention enema can effectively improve the cognitive function of patients with MHE, whereas disturbances in the enterohepatic circulation of bile acid (BAs) can induce MHE. However, the molecular mechanisms underlying the therapeutic effects of RD have not been examined from the perspective of intestinal microbiota and bile metabolomics. In this study, we investigated the effects of RD-induced retention enema on intestinal microbiota and bile metabolites in rats with CCl4- and TAA-induced MHE. RD-induced retention enema significantly improved liver function, reduced blood ammonia levels, alleviated cerebral oedema and restored cognitive function in rats with MHE. In addition, it increased the abundance of intestinal microbes; partially reversed the disorder in the composition of intestinal microbiota, including the Bifidobacterium and Bacteroides genera; and regulated BA metabolism, such as taurine combined with increased BA synthesis. In conclusion, this study highlights the potential importance of BA enterohepatic circulation for RD to improve cognitive function in MHE rats, providing a new perspective on the mechanism of this herb. The findings of this study will facilitate experimental research on RD and help to develop RD-based strategies for clinical application.PMID:37059036 | DOI:10.1016/j.jpba.2023.115392

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 7;1222:123711. doi: 10.1016/j.jchromb.2023.123711. Online ahead of print.ABSTRACTHangju (HJ), the dried flower heads of Chrysanthemum morifolium Ramat., has a significant hepatoprotective effect. However, its underlying protection mechanism against acute liver injury (ALI) has been unclear. An integrated strategy based on metabolomics with network analysis and network pharmacology was developed to explore the potential molecular mechanism of HJ on ALI protection. Firstly, differential endogenous metabolites were screened and identified by metabolomics approach and metabolic pathway analysis was performed by MetaboAnalyst. Secondly, marker metabolites were used to construct metabolite-response-enzyme-gene networks and discover hub metabolites and potential gene targets in network analysis. Thirdly, hub genes through the protein-protein interaction (PPI) network were acquired by the aid of network pharmacology. Finally, the gene targets were taken to intersect with the relevant active ingredients for validation by molecular docking. In total, 48 flavonoids were identified in HJ, which were associated with 8 potential therapeutic targets in network pharmacological analysis. Biochemistry and histopathology analysis demonstrated that HJ exerted hepatoprotective effects. 28 biomarkers were successfully identified as possible biomarkers for the prevention of ALI. The sphingolipid metabolic pathway and the glycerophospholipid metabolic pathway was considered a crucial signaling pathway by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, phosphatidylcholine and sphingomyelin were considered as hub metabolites. Twelve enzymes and 38 genes were considered as potential targets in the network analysis. Based on the combined analysis above, HJ was shown to modulate 2 key upstream targets, including PLA2G2A and PLA2G4A. Molecular docking showed that active compounds of HJ had high binding affinity with these key targets. In conclusion, the flavonoid components of HJ can inhibit PLA2 and regulate glycerophospholipid and sphingolipid metabolism pathway to delay the pathological process of ALI, which may be a potential mechanism of HJ against ALI.PMID:37059010 | DOI:10.1016/j.jchromb.2023.123711

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 6;1222:123713. doi: 10.1016/j.jchromb.2023.123713. Online ahead of print.ABSTRACTYuquan Pill (YQP) is a traditional Chinese medicine (TCM) for the treatment of type 2 diabetes (T2DM) in China for many years, and has a beneficial clinical effect. In this study, the antidiabetic mechanism of YQP was investigated for the first time from the perspective of metabolomics and intestinal microbiota. After 28 days of high-fat feeding, rats were injected intraperitoneally with streptozotocin (STZ, 35 mg/kg) followed by a single oral administration of YQP 2.16 g/kg and metformin 200 mg/kg for 5 weeks. The results showed that YQP was effectively improved insulin resistance and alleviated hyperglycemia and hyperlipidemia associated with T2DM. YQP was found to regulate metabolism and gut microbiota in T2DM rats using untargeted metabolomics and gut microbiota integration. Forty-one metabolites and five metabolic pathways were identified, including Ascorbate and aldarate metabolism, Nicotinate and nicotinamide metabolism, Galactose metabolism, Pentose phosphate pathway and Tyrosine metabolism. YQP can regulate T2DM-induced dysbacteriosis by modulating the abundance of Firmicutes, Bacteroidetes, Ruminococcus, Lactobacillus. The restorative effects of YQP in rats with T2DM have been confirmed and provide a scientific basis for the clinical treatment of diabetic patients.PMID:37059008 | DOI:10.1016/j.jchromb.2023.123713

Biosens Bioelectron. 2023 Apr 8;231:115300. doi: 10.1016/j.bios.2023.115300. Online ahead of print.ABSTRACTPlant stress responses involve a suite of genetically encoded mechanisms triggered by real-time interactions with their surrounding environment. Although sophisticated regulatory networks maintain proper homeostasis to prevent damage, the tolerance thresholds to these stresses vary significantly among organisms. Current plant phenotyping techniques and observables must be better suited to characterize the real-time metabolic response to stresses. This impedes practical agronomic intervention to avoid irreversible damage and limits our ability to breed improved plant organisms. Here, we introduce a sensitive, wearable electrochemical glucose-selective sensing platform that addresses these problems. Glucose is a primary plant metabolite, a source of energy produced during photosynthesis, and a critical molecular modulator of various cellular processes ranging from germination to senescence. The wearable-like technology integrates a reverse iontophoresis glucose extraction capability with an enzymatic glucose biosensor that offers a sensitivity of 22.7 nA/(μM·cm2), a limit of detection (LOD) of 9.4 μM, and a limit of quantification (LOQ) of 28.5 μM. The system's performance was validated by subjecting three different plant models (sweet pepper, gerbera, and romaine lettuce) to low-light and low-high temperature stresses and demonstrating critical differential physiological responses associated with their glucose metabolism. This technology enables non-invasive, non-destructive, real-time, in-situ, and in-vivo identification of early stress response in plants and provides a unique tool for timely agronomic management of crops and improving breeding strategies based on the dynamics of genome-metabolome-phenome relationships.PMID:37058961 | DOI:10.1016/j.bios.2023.115300

Talanta. 2023 Apr 11;259:124543. doi: 10.1016/j.talanta.2023.124543. Online ahead of print.ABSTRACTThe high incidence and mortality of colorectal cancer (CRC) and the lack of adequate diagnostic molecules have led to poor treatment outcomes for colorectal cancer, making it particularly important to develop methods to obtain molecular with significant diagnostic effects. Here, we proposed a whole and part study strategy (early-stage colorectal cancer as "part" and colorectal cancer as "whole") to identify specific and co-pathways of change in early-stage and colorectal cancers and to discover the determinants of colorectal cancer development. Metabolite biomarkers discovered in plasma may not necessarily reflect the pathological status of tumor tissue. To explore the determinant biomarkers associated with plasma and tumor tissue in the CRC progression, multi-omics were performed on three phases of biomarker discovery studies (discovery, identification and validation) including 128 plasma metabolomes and 84 tissue transcriptomes. Importantly, we observe that the metabolic levels of oleic acid and FA (18:2) in patients with colorectal cancer were much higher than in healthy people. Finally, biofunctional verification confirmed that oleic acid and FA (18:2) can promote the growth of colorectal cancer tumor cells and be used as plasma biomarkers for early-stage colorectal cancer. We propose a novel research strategy to discover co-pathways and important biomarkers that may be targeted for a potential role in early colorectal cancer, and our work provides a promising tool for the clinical diagnosis of colorectal cancer.PMID:37058941 | DOI:10.1016/j.talanta.2023.124543

Neoplasia. 2023 Apr 12;40:100901. doi: 10.1016/j.neo.2023.100901. Online ahead of print.ABSTRACTBACKGROUND: Approximately 95% of Colorectal cancers (CRC) consist of adenocarcinomas originating from colonic Adenomatous polyps (AP). Increasing importance in CRC occurrence and progression has been attributed to the gut microbiota; however, a huge proportion of microorganisms inhabit the human digestive system. So, to comprehensively study the microbial spatial variations and their role in CRC progression, from AP to the different CRC phases, a holistic vision is imperative, including the simultaneous evaluation of multiple niches from the gastrointestinal system. Through an integrated approach, we identified potential microbial and metabolic biomarkers, able to discriminate human CRC from AP and/or also the different Tumor node metastasis (TNM) staging. In addition, as the microbiota contributes to the production of essential metabolic products detectable in fecal samples, we analysed and compared metabolites obtained from CRC and AP patients by using a Nuclear magnetic resonance (NMR) approach.METHODS: In this observational study, saliva, tissue and stool samples from 61 patients, have been collected, including 46 CRC and 15 AP patients, age and sex-matched, undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, the microbiota in the three-district between CRC and AP patients has been characterized, as well as in different CRC TNM stages. Subsequently, proton NMR spectroscopy has been used in combination with multivariate and univariate statistical approaches, to define the fecal metabolic profile of a restricted group of CRC and AP patients.RESULTS: CRC patients display a different profile of tissue and fecal microbiota with respect to AP patients. Significant differences have been observed in CRC tissue microbial clades, with a rise of the Fusobacterium genus. In addition, significant taxa increase at the genus level has been observed in stool samples of CRC patients. Furthermore, Fusobacterium found in intestinal tissue has been positively correlated with fecal Parvimonas, for the first time. Moreover, as predicted by metagenomics pathway analysis, a significant increase of lactate (p=0.037) has been observed in the CRC fecal metabolic profiles, and positively correlated with Bifidobacterium (p=0.036). Finally, minor bacterial differences in CRC patients at stage T2 (TNM classification) have been detected, with a raise of the Spirochaetota phylum in CRC samples, with a slight increase of the Alphaproteobacteria class in fecal samples.CONCLUSION: Our results suggest the importance of microbiota communities and oncometabolites in CRC development. Further studies on CRC/AP management with a focus on CRC assessment are needed to investigate novel microbial-related diagnostic tools aimed to improve therapeutic interventions.PMID:37058886 | DOI:10.1016/j.neo.2023.100901

Biomed Pharmacother. 2023 Apr 12;162:114660. doi: 10.1016/j.biopha.2023.114660. Online ahead of print.ABSTRACTMultidrug-resistance (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a lethal gram-negative pathogen causing hospital-acquired and ventilator-associated pneumonia, which is difficult to treat. Our previous studies confirmed that baicalin, an essential bioactive component in Scutellaria baicalensis Georgi, exhibited anti-inflammatory effects in an acute pneumonia rat model induced by MDR P. aeruginosa. However, this effect of baicalin in constrast its low bioavailability, and its mechanism of action is still unknown. Thus, this study investigated whether the therapeutic effects of baicalin against MDR P. aeruginosa acute pneumonia are owing to the regulation of gut microbiota and their metabolites using pyrosequencing of the 16S rRNA genes in rat feces and metabolomics. As a result, baicalin attenuated the inflammation by acting directly on neutrophils and regulated the production of the inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10. The mechanisms were through down-regulation of TLR4 and inhibition of NF-κB. Furthermore, pyrosequencing of the 16S rRNA genes in rat feces revealed that baicalin regulated the composition of gut microbial communities. At the genus level, baicalin efficiently increased the abundance of Ligilactobacillus, Lactobacillus and Bacteroides, but decreased the abundance of Muribaculaceae and Alistipes. Further, arginine biosynthesis was analyzed as the core pathway regulated by baicalin via combination with predicting gut microbiota function and targeted metabolomics. In conclusion, this study has demonstrated that baicalin relieved inflammatory injury in acute pneumonia rat induced by MDR P. aeruginosa via arginine biosynthesis associated with gut microbiota. Baicalin could be a promising and effective adjunctive therapy for lung inflammation caused by MDR P. aeruginosa infection.PMID:37058819 | DOI:10.1016/j.biopha.2023.114660

Plant Biotechnol J. 2023 Apr 14. doi: 10.1111/pbi.14056. Online ahead of print.ABSTRACTHigh-temperature (HT) stress at flowering stage causes significant damage to soybean, including pollen abortion and fertilization failure, but few genes involved in male fertility regulation under HT stress in soybean have been characterized. Here, we demonstrated that miR156b-GmSPL2b module involved in male fertility regulation of soybean cytoplasmic male sterility (CMS)-based restorer line under HT stress. Overexpression of miR156b decreased male fertility in soybean CMS-based restorer line and its hybrid F1 with CMS line under HT stress. RNA-seq analysis found that miR156b mediated male fertility regulation in soybean under HT stress by regulating the expression of pollen development and HT response related genes. Metabolomic analysis of miR156bOE revealed reduction in flavonoid content under HT stress. Integrated transcriptomic and metabolomic analysis showed that the overexpression of miR156b caused flavonoid metabolism disorder in soybean flower bud under HT stress. Knockout of GmSPL2b also decreased the thermotolerance of soybean CMS-based restorer line during flowering. Moreover, GmSPL2b turned out to be directly bounded to the promoter of GmHSFA6b. Further verification indicated that GmHSFA6b overexpression enhanced HT tolerance in Arabidopsis during flowering. Substance content and gene expression analysis revealed that miR156b-GmSPL2b may mediate reactive oxygen species clearance by regulating flavonoid metabolism, thus participating in the regulation of male fertility in soybean under HT stress. This study not only provided important progress for understanding the molecular mechanism of miR156b-GmSPL2b regulating the male fertility of soybean CMS-based restorer line under HT stress, but also provided genetic resources and theoretical basis for creating HT-tolerant strong restorer lines.PMID:37057908 | DOI:10.1111/pbi.14056

J Agric Food Chem. 2023 Apr 14. doi: 10.1021/acs.jafc.2c07241. Online ahead of print.ABSTRACTA high-compliance dietary intervention was conducted for 2 weeks in adults aged 50 years and older to investigate the preventing aging effects of a polyphenol-probiotic-enhanced diet (P-diet) by using inflammatory biological age (IBA). Following the P-diet, levels of interleukin-6 (IL-6), IL-10, and C-reactive protein were reduced. These effects were accompanied by a significant increase in the richness of Lactobacillus and Bifidobacterium and decrease in CAG_56, as well as an increase in butyrate and acetate and decrease in lysine, uracil, and valine. We optimized a model by a back propagation artificial neural network to evaluate the degree of aging, with an R2 of 0.68. After the P-diet intervention, IBA was younger than chronological age and the inflammatory aging potential (Δage) was observably reduced by 90.12%, with change in Δage having a direct negative association with Akkermansia. Overall, P-diet may alleviate chronic low-grade inflammation and thus prevent the procession of inflammatory aging.PMID:37057839 | DOI:10.1021/acs.jafc.2c07241

Biomed Chromatogr. 2023 Apr 14:e5651. doi: 10.1002/bmc.5651. Online ahead of print.ABSTRACTCannabis is the world's most used illegal drug. The main psychoactive component is ∆-9-tetrahydrocannabinol (THC). To aid identification of cannabis-impaired individuals, a simple but effective workflow for reliable quantification of THC and its metabolites in oral fluid samples collected with the Greiner Bio-One Saliva Collection System is presented. Sampling involves rinsing the oral cavity with an extraction solution containing a citrate buffer stimulating salivary flow. Sample processing targeted the cannabinoid fraction interacting with proteins and other insoluble constituents that can be separated by centrifugation. Approximately 50% of the total cannabinoid amount included in oral fluid were recovered from the obtained pellet by extraction with acetonitrile. Liquid chromatography-tandem mass spectrometry was used for cannabinoid quantification. Fitness of the developed workflow for application in forensic and clinical cannabis testing was demonstrated by assessing multiple performance parameters, including selectivity, linearity, limits of quantification (LOQs), accuracy, precision, matrix effects, extraction recoveries, process efficiencies, and stability. Furthermore, sensitivity and specificity of the developed oral fluid-based cannabis test was demonstrated by analysing 195 samples collected either from opioid addicts or persons suspected of driving under the influence of drugs. The accuracy of identifying a person with presence of THC in blood was found to be 97.9%.PMID:37057387 | DOI:10.1002/bmc.5651