PubMed

Dtsch Med Wochenschr. 2023 Mar;148(6):331-334. doi: 10.1055/a-1924-3921. Epub 2023 Mar 6.ABSTRACTSince September 2022, there is a new, German-language glossary for the nomenclature of renal function and renal disease, aligned with international technical terms and KDIGO guidelines for a more precise and uniform description of the facts. Terms such as "renal disease," "renal insufficiency," or "acute renal failure" should be avoided and replaced with "disease" or "functional impairment."The KDIGO guideline recommends in patients with CKD stage G3a, in addition to the determination of serum creatinine, the additional determination of cystatin to confirm the CKD stage. A combination of serum creatinine and cystatin C to estimate GFR without taking into account the so-called race coefficient seems to be more accurate in African Americans than the previous eGFR formulas. However, there is no recommendation on this in international guidelines yet. For Caucasians, the formula does not change.Renal function impairment lasting more than 7 days but less than 3 months is called acute kidney disease (AKD). The AKD stage is the critical time window for therapeutic interventions to reduce the risk of progression in kidney disease.A future, expanded AKI definition incorporating biomarkers will allow patients to be divided into subclasses according to functional and structural limitations, thus mapping the two-dimensionality of AKI. By using artificial intelligence, large amounts of data from clinical parameters, blood and urine samples, histopathological and molecular markers (including proteomics and metabolomics data) can be used integratively for the graduation of CKD and thus contribute significantly to individualized therapy.PMID:36878233 | DOI:10.1055/a-1924-3921

PLoS One. 2023 Mar 6;18(3):e0281074. doi: 10.1371/journal.pone.0281074. eCollection 2023.ABSTRACTBACKGROUND: Accurate estimates of gestational age (GA) at birth are important for preterm birth surveillance but can be challenging to obtain in low income countries. Our objective was to develop machine learning models to accurately estimate GA shortly after birth using clinical and metabolomic data.METHODS: We derived three GA estimation models using ELASTIC NET multivariable linear regression using metabolomic markers from heel-prick blood samples and clinical data from a retrospective cohort of newborns from Ontario, Canada. We conducted internal model validation in an independent cohort of Ontario newborns, and external validation in heel prick and cord blood sample data collected from newborns from prospective birth cohorts in Lusaka, Zambia and Matlab, Bangladesh. Model performance was measured by comparing model-derived estimates of GA to reference estimates from early pregnancy ultrasound.RESULTS: Samples were collected from 311 newborns from Zambia and 1176 from Bangladesh. The best-performing model accurately estimated GA within about 6 days of ultrasound estimates in both cohorts when applied to heel prick data (MAE 0.79 weeks (95% CI 0.69, 0.90) for Zambia; 0.81 weeks (0.75, 0.86) for Bangladesh), and within about 7 days when applied to cord blood data (1.02 weeks (0.90, 1.15) for Zambia; 0.95 weeks (0.90, 0.99) for Bangladesh).CONCLUSIONS: Algorithms developed in Canada provided accurate estimates of GA when applied to external cohorts from Zambia and Bangladesh. Model performance was superior in heel prick data as compared to cord blood data.PMID:36877673 | DOI:10.1371/journal.pone.0281074

Calcif Tissue Int. 2023 Mar 6. doi: 10.1007/s00223-023-01069-0. Online ahead of print.ABSTRACTMounting evidence has supported osteoporosis (OP) as a metabolic disorder. Recent metabolomics studies have discovered numerous metabolites related to bone mineral density (BMD). However, the causal effects of metabolites on BMD at distinct sites remained underexplored. Leveraging genome-wide association datasets, we conducted two-sample Mendelian randomization (MR) analyses to investigate the causal relationship between 486 blood metabolites and bone mineral density at five skeletal sites including heel (H), total body (TB), lumbar spine (LS), femoral neck (FN), and ultra-distal forearm (FA). Sensitivity analyses were performed to test the presence of the heterogeneity and the pleiotropy. To exclude the influences of reverse causation, genetic correlation, and linkage disequilibrium (LD), we further performed reverse MR, linkage disequilibrium regression score (LDSC), and colocalization analyses. In the primary MR analyses, 22, 10, 3, 7, and 2 metabolite associations were established respectively for H-BMD, TB-BMD, LS-BMD, FN-BMD, and FA-BMD at the nominal significance level (IVW, P < 0.05) and passing sensitivity analyses. Among these, one metabolite, androsterone sulfate showed a strong effect on four out of five BMD phenotypes (Odds ratio [OR] for H-BMD = 1.045 [1.020, 1.071]; Odds ratio [OR] for TB-BMD = 1.061 [1.017, 1.107]; Odds ratio [OR] for LS-BMD = 1.088 [1.023, 1.159]; Odds ratio [OR] for FN-BMD = 1.114 [1.054, 1.177]). Reverse MR analysis provided no evidence for the causal effects of BMD measurements on these metabolites. Colocalization analysis have found that several metabolite associations might be driven by shared genetic variants such as mannose for TB-BMD. This study identified some metabolites causally related to BMD at distinct sites and several key metabolic pathways, which shed light on predictive biomarkers and drug targets for OP.PMID:36877247 | DOI:10.1007/s00223-023-01069-0

Microbiol Spectr. 2023 Mar 6:e0234422. doi: 10.1128/spectrum.02344-22. Online ahead of print.ABSTRACTDiabetic mellitus nephropathy (DMN) is a serious complication of diabetes and a major health concern. Although the pathophysiology of diabetes mellitus (DM) leading to DMN is uncertain, recent evidence suggests the involvement of the gut microbiome. This study aimed to determine the relationships among gut microbial species, genes, and metabolites in DMN through an integrated clinical, taxonomic, genomic, and metabolomic analysis. Whole-metagenome shotgun sequencing and nuclear magnetic resonance metabolomic analyses were performed on stool samples from 15 patients with DMN and 22 healthy controls. Six bacterial species were identified to be significantly elevated in the DMN patients after adjusting for age, sex, body mass index, and estimated glomerular filtration rate (eGFR). Multivariate analysis found 216 microbial genes and 6 metabolites (higher valine, isoleucine, methionine, valerate, and phenylacetate levels in the DMN group and higher acetate levels in the control group) that were differentially present between the DMN and control groups. Integrated analysis of all of these parameters and clinical data using the random-forest model showed that methionine and branched-chain amino acids (BCAAs) were among the most significant features, next to the eGFR and proteinuria, in differentiating the DMN group from the control group. Metabolic pathway gene analysis of BCAAs and methionine also revealed that many genes involved in the biosynthesis of these metabolites were elevated in the six species that were more abundant in the DMN group. The suggested correlation among taxonomic, genetic, and metabolic features of the gut microbiome would expand our understanding of gut microbial involvement in the pathogenesis of DMN and may provide potential therapeutic targets for DMN. IMPORTANCE Whole metagenomic sequencing uncovered specific members of the gut microbiota associated with DMN. The gene families derived from the discovered species are involved in the metabolic pathways of methionine and branched-chain amino acids. Metabolomic analysis using stool samples showed increased methionine and branched-chain amino acids in DMN. These integrative omics results provide evidence of the gut microbiota-associated pathophysiology of DMN, which can be further studied for disease-modulating effects via prebiotics or probiotics.PMID:36877076 | DOI:10.1128/spectrum.02344-22

Carbohydr Polym. 2023 Jan 1;299:120156. doi: 10.1016/j.carbpol.2022.120156. Epub 2022 Oct 7.ABSTRACTChitooligosaccharides (COS) have many bioactive functions and favorable prospects in the fields of biomedicine and functional foods. In this study, COS was found to significantly improve the survival rate of neonatal necrotizing enterocolitis (NEC) model rats, alter the composition of the intestinal microbiota, inhibit the expression of inflammatory cytokines, and alleviate intestinal pathological injury. In addition, COS also increased the abundance of Akkermansia, Bacteroides, and Clostridium sensu stricto 1 in the intestines of normal rats (the normal rat model is more universal). The in vitro fermentation results found that COS was degraded by the human gut microbiota to promote the abundance of Clostridium sensu stricto 1 and produced numerous short-chain fatty acids (SCFAs). In vitro metabolomic analysis revealed that COS catabolism was associated with significant increases in 3-hydroxybutyrate acid and γ-aminobutyric acid. This study provides evidence for the potential of COS as a prebiotic in food products and to ameliorate NEC development in neonatal rats.PMID:36876780 | DOI:10.1016/j.carbpol.2022.120156

Eur Rev Med Pharmacol Sci. 2023 Feb;27(4):1443-1449. doi: 10.26355/eurrev_202302_31384.ABSTRACTOBJECTIVE: Short-chain fatty acids (SCFAs) are microbial derived metabolites, which have multiple beneficial properties. The amount of SCFAs depends on several factors, such as age, diet (mainly intake of dietary fiber), and overall health condition. The normal proportion between SCFAs is 3:1:1 for acetate, proprionate and butyrate, respectively. In colorectal cancer (CRC) patients, microbiota alterations have been shown. Consequently, metabolome within the gut might change to a large extent. Therefore, the aim of this study was to analyse the content of SCFAs and the proportion between SCFAs in the stool obtained from CRC patients in preoperative period.PATIENTS AND METHODS: This study included 15 patients with CRC in preoperative period. The stool samples were taken and stored at -80°C in the Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Poland. The analysis of SCFAs from stool samples was conducted by means of gas chromatography.RESULTS: This study included mainly males (66.67%, n=10). In all patients, there was abnormal proportion between SCFAs. The extremely higher concentration of butyrate was noted in 2 samples (13.33%) compared to the rest of patients. However, based on normal proportion between SCFAs, the results <1 for butyrate were noted in 93.33% of patients.CONCLUSIONS: SCFAs pool is altered in CRC patients, among others characterized by low level of butyrate. It should be considered to administer butyrate supplementation to CRC patients especially prior to surgery to support an appropriate preparation to this treatment.PMID:36876684 | DOI:10.26355/eurrev_202302_31384

Front Microbiol. 2023 Feb 16;14:1128394. doi: 10.3389/fmicb.2023.1128394. eCollection 2023.ABSTRACTIndustrial production of Gouda cheeses mostly relies on a rotated use of different mixed-strain lactic acid bacteria starter cultures to avoid phage infections. However, it is unknown how the application of these different starter culture mixtures affect the organoleptic properties of the final cheeses. Therefore, the present study assessed the impact of three different starter culture mixtures on the batch-to-batch variations among Gouda cheeses from 23 different batch productions in the same dairy company. Both the cores and rinds of all these cheeses were investigated after 36, 45, 75, and 100 weeks of ripening by metagenetics based on high-throughput full-length 16S rRNA gene sequencing accompanied with an amplicon sequence variant (ASV) approach as well as metabolite target analysis of non-volatile and volatile organic compounds. Up to 75 weeks of ripening, the acidifying Lactococcus cremoris and Lactococcus lactis were the most abundant bacterial species in the cheese cores. The relative abundance of Leuconostoc pseudomesenteroides was significantly different for each starter culture mixture. This impacted the concentrations of some key metabolites, such as acetoin produced from citrate, and the relative abundance of non-starter lactic acid bacteria (NSLAB). Cheeses with the least Leuc. pseudomesenteroides contained more NSLAB, such as Lacticaseibacillus paracasei that was taken over by Tetragenococcus halophilus and Loigolactobacillus rennini upon ripening time. Taken together, the results indicated a minor role of leuconostocs in aroma formation but a major impact on the growth of NSLAB. The relative abundance of T. halophilus (high) and Loil. rennini (low) increased with ripening time from rind to core. Two main ASV clusters of T. halophilus could be distinguished, which were differently correlated with some metabolites, both beneficial (regarding aroma formation) and undesirable ones (biogenic amines). A well-chosen T. halophilus strain could be a candidate adjunct culture for Gouda cheese production.PMID:36876114 | PMC:PMC9978159 | DOI:10.3389/fmicb.2023.1128394

Front Microbiol. 2023 Feb 15;14:1117355. doi: 10.3389/fmicb.2023.1117355. eCollection 2023.ABSTRACTOrganic and microbial fertilizers have potential advantages over inorganic fertilizers in improving soil fertility and crop yield without harmful side-effects. However, the effects of these bio-organic fertilizers on the soil microbiome and metabolome remain largely unknown, especially in the context of bamboo cultivation. In this study, we cultivated Dendrocalamus farinosus (D. farinosus) plants under five different fertilization conditions: organic fertilizer (OF), Bacillus amyloliquefaciens bio-fertilizer (Ba), Bacillus mucilaginosus Krassilnikov bio-fertilizer (BmK), organic fertilizer plus Bacillus amyloliquefaciens bio-fertilizer (OFBa), and organic fertilizer plus Bacillus mucilaginosus Krassilnikov bio-fertilizer (OFBmK). We conducted 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC-MS) to evaluate the soil bacterial composition and soil metabolic activity in the different treatment groups. The results demonstrate that all the fertilization conditions altered the soil bacterial community composition. Moreover, the combination of organic and microbial fertilizers (i.e., in the OFBa and OFBmK groups) significantly affected the relative abundance of soil bacterial species; the largest number of dominant microbial communities were found in the OFBa group, which were strongly correlated with each other. Additionally, non-targeted metabolomics revealed that the levels of soil lipids and lipid-like molecules, and organic acids and their derivatives, were greatly altered under all treatment conditions. The levels of galactitol, guanine, and deoxycytidine were also markedly decreased in the OFBa and OFBmK groups. Moreover, we constructed a regulatory network to delineated the relationships between bamboo phenotype, soil enzymatic activity, soil differential metabolites, and dominant microbial. The network revealed that bio-organic fertilizers promoted bamboo growth by modifying the soil microbiome and metabolome. Accordingly, we concluded that the use of organic fertilizers, microbial fertilizers, or their combination regulated bacterial composition and soil metabolic processes. These findings provide new insights into how D. farinosus-bacterial interactions are affected by different fertilization regiments, which are directly applicable to the agricultural cultivation of bamboo.PMID:36876063 | PMC:PMC9975161 | DOI:10.3389/fmicb.2023.1117355

Front Mol Biosci. 2023 Feb 15;10:1111482. doi: 10.3389/fmolb.2023.1111482. eCollection 2023.ABSTRACTCOVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.PMID:36876049 | PMC:PMC9975567 | DOI:10.3389/fmolb.2023.1111482

Front Mol Biosci. 2023 Feb 15;10:1119588. doi: 10.3389/fmolb.2023.1119588. eCollection 2023.NO ABSTRACTPMID:36876048 | PMC:PMC9975730 | DOI:10.3389/fmolb.2023.1119588

Front Mol Biosci. 2023 Feb 17;10:1128542. doi: 10.3389/fmolb.2023.1128542. eCollection 2023.ABSTRACTTrichinella infections have been documented globally and have been detected in wild and/or domestic animals except Antarctica. There is paucity of information in the metabolic responses of hosts during Trichinella infections and biomarkers for infection that can be used in the diagnosis of the disease. The current study aimed to apply a non-targeted metabolomic approach to identify Trichinella zimbabwensis biomarkers including metabolic response from sera of infected Sprague-Dawley rats. Fifty-four male Sprague-Dawley rats were randomly assigned into T. zimbabwensis infected group (n = 36) and the non-infected control (n = 18). Results from the study showed that the metabolic signature of T. zimbabwensis infection consists of enriched methyl histidine metabolism, disturbance of the liver urea cycle, impeded TCA cycle, and upregulation of gluconeogenesis metabolism. The observed disturbance in the metabolic pathways was attributed to the effects caused by the parasite during its migration to the muscles resulting in downregulation of amino acids intermediates in the Trichinella-infected animals, and therefore affecting energy production and degradation of biomolecules. It was concluded that T. zimbabwensis infection caused an upregulation of amino acids; pipecolic acid, histidine, and urea, and upregulation of glucose and meso-Erythritol. Moreover, T. zimbabwensis infection caused upregulation of the fatty acids, retinoic acid, and acetic acid. These findings highlight the potential of metabolomics as a novel approach for fundamental investigations of host-pathogen interactions as well as for disease progression and prognosis.PMID:36876045 | PMC:PMC9983363 | DOI:10.3389/fmolb.2023.1128542

Curr Res Food Sci. 2023 Feb 18;6:100464. doi: 10.1016/j.crfs.2023.100464. eCollection 2023.ABSTRACTThe prevalence of obesity is rapidly increasing and poses serious health risks accompanied by a decrease in life expectancy and quality of life. Therefore, the therapeutic potential of natural-derived nutraceuticals against obesity and its comorbidities needs to be explored. Molecular inhibition of lipase enzymes and fat mass and obesity-associated (FTO) protein has attracted some recent interest in efforts to find antiobesity agents. This study aims to innovate a fermented drink from Clitoria ternatea kombucha (CTK), find out their metabolites profile, and determine the antiobesity potential through a molecular docking study. The CTK formulation refers to previous research while the metabolites profile was determined using HPLC-ESI-HRMS/MS. Major compounds were selected based on best match value > 99.0% of the M/Z cloud database. A total of 79 compounds were identified in CTK, and 13 ideal compounds were selected to be simulated in the molecular docking study against human pancreatic lipase, α-amylase, α-glucosidase, porcine pancreatic lipase, and FTO proteins. The study found that Kaempferol, Quercetin-3β-D-glucoside, Quercetin, Dibenzylamine, and α-Pyrrolidinopropiophenone showed the best potential as functional antiobesity compounds since their affinity value ranked high in each respective receptor. In conclusion, the major compounds of CTK metabolites have the potential to be promising functional foods against obesity. However, further in vitro and in vivo studies should validate these health benefits.PMID:36875892 | PMC:PMC9976213 | DOI:10.1016/j.crfs.2023.100464

Front Nutr. 2023 Feb 16;10:1110536. doi: 10.3389/fnut.2023.1110536. eCollection 2023.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.PMID:36875849 | PMC:PMC9978194 | DOI:10.3389/fnut.2023.1110536

Front Nutr. 2023 Feb 16;10:1104446. doi: 10.3389/fnut.2023.1104446. eCollection 2023.ABSTRACTCordycepin, an important active substance in Cordyceps militaris, possesses antiviral and other beneficial activities. In addition, it has been reported to effectively promote the comprehensive treatment of COVID-19 and thus has become a research hotspot. The addition of naphthalene acetic acid (NAA) is known to significantly improve the yield of cordycepin; however, its related molecular mechanism remains unclear. We conducted a preliminary study on C. militaris with different concentrations of NAA. We found that treatment with different concentrations of NAA inhibited the growth of C. militaris, and an increase in its concentration significantly improved the cordycepin content. In addition, we conducted a transcriptome and metabolomics association analysis on C. militaris treated with NAA to understand the relevant metabolic pathway of cordycepin synthesis under NAA treatment and elucidate the relevant regulatory network of cordycepin synthesis. Weighted gene co-expression network analysis (WGCNA), transcriptome, and metabolome association analysis revealed that genes and metabolites encoding cordycepin synthesis in the purine metabolic pathway varied significantly with the concentration of NAA. Finally, we proposed a metabolic pathway by analyzing the relationship between gene-gene and gene-metabolite regulatory networks, including the interaction of cordycepin synthesis key genes; key metabolites; purine metabolism; TCA cycle; pentose phosphate pathway; alanine, aspartate, and glutamate metabolism; and histidine metabolism. In addition, we found the ABC transporter pathway to be significantly enriched. The ABC transporters are known to transport numerous amino acids, such as L-glutamate, and participate in the amino acid metabolism that affects the synthesis of cordycepin. Altogether, multiple channels work together to double the cordycepin yield, thereby providing an important reference for the molecular network relationship between the transcription and metabolism of cordycepin synthesis.PMID:36875834 | PMC:PMC9977999 | DOI:10.3389/fnut.2023.1104446

Front Aging Neurosci. 2023 Feb 17;15:1108205. doi: 10.3389/fnagi.2023.1108205. eCollection 2023.ABSTRACTOBJECTIVE: To investigate the role of gut microbiota and metabolites in POCD in elderly orthopedic patients, and screen the preoperative diagnostic indicators of gut microbiota in elderly POCD.METHOD: 40 elderly patients undergoing orthopedic surgery were enrolled and divided into Control group and POCD group following neuropsychological assessments. Gut microbiota was determined by 16S rRNA MiSeq sequencing, and metabolomics of GC-MS and LC-MS was used to screen the differential metabolites. We then analyzed the pathways enriched by metabolites.RESULT: There was no difference in alpha or beta diversity between Control group and POCD group. There were significant differences in 39 ASV and 20 genera bacterium in the relative abundance. Significant diagnostic efficiency analyzed by the ROC curves were found in 6 genera bacterium. Differential metabolites in the two groups including acetic acid, arachidic acid, pyrophosphate etc. were screened out and enriched to certain metabolic pathways which impacted the cognition function profoundly.CONCLUSION: Gut microbiota disorders exist preoperatively in the elderly POCD patients, by which there could be a chance to predict the susceptible population.CLINICAL TRIAL REGISTRATION: [http://www.chictr.org.cn/edit.aspx?pid=133843&htm=4], identifier [ChiCTR2100051162].PMID:36875700 | PMC:PMC9981628 | DOI:10.3389/fnagi.2023.1108205

Front Plant Sci. 2023 Feb 15;14:1132936. doi: 10.3389/fpls.2023.1132936. eCollection 2023.ABSTRACTINTRODUCTION: The bulb of Fritillaria hupehensis, a traditional cough and expectorant medicine, is usually harvested from June to September according to traditional cultivation experience, without practical scientific guidance. Although steroidal alkaloid metabolites have been identified in F. hupehensis, the dynamic changes in their levels during bulb development and their molecular regulatory mechanisms are poorly understood.METHODS: In this study, integrative analyses of the bulbus phenotype, bioactive chemical investigations, and metabolome and transcriptome profiles were performed to systematically explore the variations in steroidal alkaloid metabolite levels and identify the genes modulating their accumulation and the corresponding regulatory mechanisms.RESULTS: The results showed that weight, size, and total alkaloid content of the regenerated bulbs reached a maximum at IM03 (post-withering stage, early July), whereas peiminine content reached a maximum at IM02 (withering stage, early June). There were no significant differences between IM02 and IM03, indicating that regenerated bulbs could be harvested appropriately in early June or July. Peiminine, peimine, tortifoline, hupehenine, korseveramine, delafrine, hericenone N-oxide, korseveridine, puqiedinone, pingbeinone, puqienine B, puqienine E, pingbeimine A, jervine, and ussuriedine levels were upregulated in IM02 and IM03, compared with IM01 (vigorous growth stage, early April). The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the accumulation of steroidal alkaloid metabolites mainly occurred prior to IM02. HMGR1, DXR, CAS1, CYP 90A1, and DET2 may play a positive role in peiminine, peimine, hupehenine, korseveramine, korseveridine, hericenone N-oxide, puqiedinone, delafrine, tortifoline, pingbeinone, puqienine B, puqienine E, pingbeimine A, jervine, and ussuriedine biosynthesis, whereas the downregulation of FPS1, SQE and 17-DHCR may lead to a reduction in peimisine levels. Weighted gene correlation network analysis showed that CYP 74A2-1, CYP 74A2-2, CYP 71A26-1, CYP 71A26-2, and CYP74A were negatively correlated with peiminine and pingbeimine A, whereas CYP R and CYP707A1 were positively correlated. . CYP 74A2-1 and CYP 74A2-2 may play a negative role in peimine and korseveridine biosynthesis, whereas CYP R plays a positive role. In addition, the highly expressed C2H2, HSF, AP2/ERF, HB, GRAS, C3H, NAC, MYB-related transcription factors (TFs), GARP-G2-like TFs, and WRKY may play positive roles in the accumulation of peiminine, peimine, korseveridine, and pingbeimine A.DISCUSSION: These results provide new insights into scientific harvesting of F. hupehensis.PMID:36875619 | PMC:PMC9975545 | DOI:10.3389/fpls.2023.1132936

Front Plant Sci. 2023 Feb 15;14:1120573. doi: 10.3389/fpls.2023.1120573. eCollection 2023.NO ABSTRACTPMID:36875606 | PMC:PMC9975924 | DOI:10.3389/fpls.2023.1120573

Oncoimmunology. 2023 Feb 17;12(1):2180237. doi: 10.1080/2162402X.2023.2180237. eCollection 2023.ABSTRACTAccumulating evidence indicates that Toll-like receptor (TLR) agonists proficiently (re)instore cancer immunosurveillance as immunological adjuvants. So far, three TLR agonists have been approved by regulatory agencies for use in oncological applications. Additionally, these immunotherapeutics have been extensively investigated over the past few years. Multiple clinical trials are currently evaluating the combination of TLR agonists with chemotherapy, radiotherapy, or different immunotherapies. Moreover, antibodies targeting tumor-enriched surface proteins that have been conjugated to TLR agonists are being developed to stimulate anticancer immune responses specifically within the tumor microenvironment. Solid preclinical and translational results support the favorable immune-activating effects of TLR agonists. Here, we summarize recent preclinical and clinical advances in the development of TLR agonists for anticancer immunotherapy.PMID:36875550 | PMC:PMC9980677 | DOI:10.1080/2162402X.2023.2180237

Front Cell Infect Microbiol. 2023 Feb 15;13:1013809. doi: 10.3389/fcimb.2023.1013809. eCollection 2023.ABSTRACTBACKGROUND: Differences in bronchial microbiota composition have been found to be associated with asthma; however, it is still unclear whether these findings can be applied to recurrent wheezing in infants especially with aeroallergen sensitization.OBJECTIVES: To determine the pathogenesis of atopic wheezing in infants and to identify diagnostic biomarkers, we analyzed the bronchial bacterial microbiota of infants with recurrent wheezing and with or without atopic diseases using a systems biology approach.METHODS: Bacterial communities in bronchoalveolar lavage samples from 15 atopic wheezing infants, 15 non-atopic wheezing infants, and 18 foreign body aspiration control infants were characterized using 16S rRNA gene sequencing. The bacterial composition and community-level functions inferred from between-group differences from sequence profiles were analyzed.RESULTS: Both α- and β-diversity differed significantly between the groups. Compared to non-atopic wheezing infants, atopic wheezing infants showed a significantly higher abundance in two phyla (Deinococcota and unidentified bacteria) and one genus (Haemophilus) and a significantly lower abundance in one phylum (Actinobacteria). The random forest predictive model of 10 genera based on OTU-based features suggested that airway microbiota has diagnostic value for distinguishing atopic wheezing infants from non-atopic wheezing infants. PICRUSt2 based on KEGG hierarchy (level 3) revealed that atopic wheezing-associated differences in predicted bacterial functions included cytoskeleton proteins, glutamatergic synapses, and porphyrin and chlorophyll metabolism pathways.CONCLUSION: The differential candidate biomarkers identified by microbiome analysis in our work may have reference value for the diagnosis of wheezing in infants with atopy. To confirm that, airway microbiome combined with metabolomics analysis should be further investigated in the future.PMID:36875523 | PMC:PMC9975506 | DOI:10.3389/fcimb.2023.1013809

Front Endocrinol (Lausanne). 2023 Feb 16;14:1060470. doi: 10.3389/fendo.2023.1060470. eCollection 2023.ABSTRACTOBJECTIVE: Sepsis is a life-threatening condition secondary to infection that evolves into a dysregulated host response and is associated with acute organ dysfunction. Sepsis-induced cardiac dysfunction is one of the most complex organ failures to characterize. This study performed comprehensive metabolomic profiling that distinguished between septic patients with and without cardiac dysfunction.METHOD: Plasma samples collected from 80 septic patients were analysed by untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics. Principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA), and orthogonal partial least square discriminant analysis (OPLS-DA) were applied to analyse the metabolic model between septic patients with and without cardiac dysfunction. The screening criteria for potential candidate metabolites were as follows: variable importance in the projection (VIP) >1, P < 0.05, and fold change (FC) > 1.5 or < 0.7. Pathway enrichment analysis further revealed associated metabolic pathways. In addition, we constructed a subgroup metabolic analysis between the survivors and non-survivors according to 28-day mortality in the cardiac dysfunction group.RESULTS: Two metabolite markers, kynurenic acid and gluconolactone, could distinguish the cardiac dysfunction group from the normal cardiac function group. Two metabolites, kynurenic acid and galactitol, could distinguish survivors and non-survivors in the subgroup analysis. Kynurenic acid is a common differential metabolite that could be used as a candidate for both diagnosis and prognosis for septic patients with cardiac dysfunction. The main associated pathways were amino acid metabolism, glucose metabolism and bile acid metabolism.CONCLUSION: Metabolomic technology could be a promising approach for identifying diagnostic and prognostic biomarkers of sepsis-induced cardiac dysfunction.PMID:36875476 | PMC:PMC9978788 | DOI:10.3389/fendo.2023.1060470