PubMed

Appl Environ Microbiol. 2023 Apr 11:e0040623. doi: 10.1128/aem.00406-23. Online ahead of print.ABSTRACTClostridium thermocellum, a promising candidate for consolidated bioprocessing, has been subjected to numerous engineering strategies for enhanced bioethanol production. Measurements of intracellular metabolites at substrate concentrations high enough (>50 g/L) to allow the production of industrially relevant titers of ethanol would inform efforts toward this end but have been difficult due to the production of a viscous substance that interferes with the filtration and quenching steps during metabolite extraction. To determine whether this problem is unique to C. thermocellum, we performed filtration experiments with other organisms that have been engineered for high-titer ethanol production, including Escherichia coli and Thermoanaerobacterium saccharolyticum. We addressed the problem through a series of improvements, including active pH control (to reduce problems with viscosity), investigation of different filter materials and pore sizes (to increase the filtration capacity), and correction for extracellular metabolite concentrations, and we developed a technique for more accurate intracellular metabolite measurements at elevated substrate concentrations. IMPORTANCE The accurate measurement of intracellular metabolites (metabolomics) is an integral part of metabolic engineering for the enhanced production of industrially important compounds and a useful technique to understand microbial physiology. Previous work tended to focus on model organisms under laboratory conditions. As we try to perform metabolomic studies with a wider range of organisms under conditions that more closely represent those found in nature or industry, we have found limitations in existing techniques. For example, fast filtration is an important step in quenching metabolism in preparation for metabolite extraction; however, it does not work for cultures of C. thermocellum at high substrate concentrations. In this work, we characterize the extent of the problem and develop techniques to overcome it.PMID:37039651 | DOI:10.1128/aem.00406-23

Elife. 2023 Apr 11;12:e81080. doi: 10.7554/eLife.81080. Online ahead of print.ABSTRACTOngoing climate change has caused rapidly increasing temperatures, and an unprecedented decline in seawater pH, known as ocean acidification. Increasing temperatures are redistributing species towards higher and cooler latitudes which are most affected by ocean acidification. Whilst the persistence of intertidal species in cold environments is related to their capacity to resist sub-zero air temperatures, studies have never considered the interacting impacts of ocean acidification and freeze stress on species survival and distribution. Here, a full-factorial experiment was used to study whether ocean acidification increases mortality in subtidal Mytilus trossulus and subtidal M. galloprovincialis, and intertidal M. trossulus following sub-zero air temperature exposure. We examined physiological processes behind variation in freeze tolerance using 1H NMR metabolomics, analyses of fatty acids, and amino acid composition. We show that low pH conditions (pH = 7.5) significantly decrease freeze tolerance in both intertidal and subtidal populations of Mytilus spp. Under current day pH conditions (pH = 7.9), intertidal M. trossulus was more freeze tolerant than subtidal M. trossulus and subtidal M. galloprovincialis. Conversely, under low pH conditions, subtidal M. trossulus was more freeze tolerant than the other mussel categories. Differences in the concentration of various metabolites (cryoprotectants), or in the composition of amino acids and cell membrane phospholipid fatty acids could not explain the decrease in survival. These results suggest that ocean acidification can offset the poleward range expansions facilitated by warming, and that reduced freeze tolerance could result in a range contraction if temperatures become lethal at the equatorward edge.PMID:37039622 | DOI:10.7554/eLife.81080

Am J Physiol Lung Cell Mol Physiol. 2023 Apr 11. doi: 10.1152/ajplung.00439.2022. Online ahead of print.ABSTRACTRadiation-induced lung injury is a consequence of therapeutic irradiation (TR) for thoracic cancers. Studies report that up to 80% of patients who undergo TR will have CT-detectable interstitial lung abnormalities, and strategies to limit the risk of RILI may make radiotherapy less effective at treating cancer. Our lab and others have reported that lung tissue from patients with idiopathic pulmonary fibrosis exhibit metabolic defects including increased glycolysis and lactate production. Here, we hypothesized that patients with radiation-induced lung damage will exhibit distinct changes in lung metabolism that may be associated with incidence of fibrosis. Using liquid chromatography/tandem mass spectrometry to identify metabolic compounds, we analyzed exhaled breath condensate (EBC) in subjects with CT-confirmed lung lesions after TR for lung cancer, compared to healthy subjects, smokers, and cancer patients who had not yet received TR. The lung metabolomic profile of the fibrosis case group was significantly different from the 3 control groups. Along with increased levels of lactate, pathway enrichment analysis revealed that EBC from the case patients exhibited upregulations of the fatty acid oxidation and glutamate pathways. As radiation induces aerobic glycolysis and production of lactate which drives myofibroblast differentiation, our results support the hypothesis that preferential conversion of pyruvate to lactate deprives the tricarboxylic acid cycle of a key input, requiring compensatory upregulation of alternative energy inputs to meet the metabolic demands of chronic wound repair. Utilizing an 'omics' approach to probe lung disease in a non-invasive manner could inform future mechanistic investigations and development of novel therapeutic targets.PMID:37039378 | DOI:10.1152/ajplung.00439.2022

Food Funct. 2023 Apr 11. doi: 10.1039/d2fo03722j. Online ahead of print.ABSTRACTAs a class of bioactive and toxic compounds widely present in foodstuffs, the health effects of dietary exposure to β-carboline heterocyclic amines (HAs) have not been elucidated. Based on our previous research that a typical β-carboline HA (harmane) affects blood glucose metabolism and organ dysfunction, the present study mainly focused on the health effects of dietary exposure to harmane in diabetic Goto-Kakizaki (GK) rats. Twenty-four GK rats were administered daily with harmane (0.1 mg per kg body weight) for eight weeks. A comprehensive evaluation of the health effects of harmane was conducted on serum biochemistry, histopathology, and GC-TOF-MS-based metabolomics. The results showed that harmane exerts non-significant effects on the blood glucose metabolism of GK rats. However, it did cause pathological damage to gastrocnemius nerves and showed adverse effects on brain neurons by significantly activating astrocytes and downregulating brain-derived neurotrophic factor (BDNF), which are potential mechanisms related to the disruption of the normal glutamine-glutamate/γ-aminobutyric acid cycle. Moreover, an increased value of AST and urea, alterations in the amino acid, carbohydrate, purine, pyrimidine, and gut microbiota metabolism as well as the tricarboxylic acid (TCA) cycle could be associated with kidney, liver, and gut dysfunction. Our results suggest that given the role of harmane in nerve injury in GK rats, reducing the production and consumption of β-carboline heterocyclic amines in our daily diets should be considered.PMID:37039336 | DOI:10.1039/d2fo03722j

Mol Omics. 2023 Apr 11. doi: 10.1039/d3mo00015j. Online ahead of print.ABSTRACTRoxadustat (FG-4592) is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) prescribed to patients with low hemoglobin associated with chronic kidney disease. Due to the various HIF-mediated adaptive responses, FG-4592 has attracted significant interest for therapeutic use against various diseases. However, the clinical application of Roxadustat remains limited due to a lack of understanding of its underlying mechanisms. Herein, we performed label-free quantitative liquid chromatography with tandem mass spectrometry (LC-MS-MS) proteomics and un-targeted metabolomics to study the protein and metabolite alterations in the urine of renal anemia patients before and after Roxadustat therapy. The results were validated by parallel reaction monitoring (PRM). A total of 46 proteins (including 15 upregulated and 31 downregulated proteins) and 207 metabolites were significantly altered after Roxadustat treatment in urine samples obtained from renal anemia patients. Then, the altered proteins were further validated by PRM. Finally, proteomics combined with metabolomics analysis revealed that the Ras signalling pathway, cysteine and methionine metabolism, arginine and proline metabolism, and cholesterol metabolism were the main pathways altered by Roxadustat treatment. The multi-omics analysis revealed that Roxadustat could alter the protein expression and reverse the potential metabolic changes to exert hypotensive, lipid metabolic regulation, and renoprotective effects in clinical practice.PMID:37039271 | DOI:10.1039/d3mo00015j

Food Funct. 2023 Apr 11. doi: 10.1039/d2fo03933h. Online ahead of print.ABSTRACTSulfated polysaccharides from sea cucumber Stichopus japonicus (SCSPsj) have been found to modulate the gut microbiota by promoting the growth of probiotics. However, the effects of the combination of SCSPsj and probiotics are still less known. Thus, the present study aimed to investigate the effects of SCSPsj and Lactobacillus gasseri on gut microbiota-altered mice through gut microbiota and metabolomics analysis. In the present study, supplementation with SCSPsj, L. gasseri or the combination of SCSPsj and L. gasseri could effectively ameliorate the body weight gain and fat accumulation in gut microbiota-altered mice treated with low-dose penicillin. The better effect of the combination of SCSPsj and L. gasseri is attributed to the synergistic effect of SCSPsj and L. gasseri. 16S rRNA sequencing revealed that the combination of SCSPsj and L. gasseri can synergistically improve gut microbiota dysbiosis by increasing Lactobacillus and reducing Coriobacteriaceae_UCG-002. Furthermore, metabolomics results revealed that the combination of SCSPsj and L. gasseri can alleviate metabolic disorders by reducing the levels of lipid and lipid-like molecules in the serum samples, such as trans-vaccenic acid and 3β-hydroxy-5-cholestene. Our findings have proved that the combination of SCSPsj and L. gasseri can benefit host health attributed to the synergistic effect, which is conducive to further application in functional food.PMID:37039235 | DOI:10.1039/d2fo03933h

Gigascience. 2022 Dec 28;12:giad021. doi: 10.1093/gigascience/giad021.ABSTRACTMass spectrometry imaging (MSI), which localizes molecules in a tag-free, spatially resolved manner, is a powerful tool for the understanding of underlying biochemical mechanisms of biological phenomena. When analyzing MSI data, it is essential to delineate regions of interest (ROIs) that correspond to tissue areas of different anatomical or pathological labels. Spatial segmentation, obtained by clustering MSI pixels according to their mass spectral similarities, is a popular approach to automate ROI definition. However, how to select the number of clusters (#Clusters), which determines the granularity of segmentation, remains to be resolved, and an inappropriate #Clusters may lead to ROIs not biologically real. Here we report a multimodal fusion strategy to enable an objective and trustworthy selection of #Clusters by utilizing additional information from corresponding histology images. A deep learning-based algorithm is proposed to extract "histomorphological feature spectra" across an entire hematoxylin and eosin image. Clustering is then similarly performed to produce histology segmentation. Since ROIs originating from instrumental noise or artifacts would not be reproduced cross-modally, the consistency between histology and MSI segmentation becomes an effective measure of the biological validity of the results. So, #Clusters that maximize the consistency is deemed as most probable. We validated our strategy on mouse kidney and renal tumor specimens by producing multimodally corroborated ROIs that agreed excellently with ground truths. Downstream analysis based on the said ROIs revealed lipid molecules highly specific to tissue anatomy or pathology. Our work will greatly facilitate MSI-mediated spatial lipidomics, metabolomics, and proteomics research by providing intelligent software to automatically and reliably generate ROIs.PMID:37039115 | DOI:10.1093/gigascience/giad021

Crit Rev Food Sci Nutr. 2023 Apr 11:1-29. doi: 10.1080/10408398.2023.2197066. Online ahead of print.ABSTRACTProbiotics are amply studied and applied dietary supplements of greater consumer acceptance. Nevertheless, the emerging evidence on probiotics-mediated potential risks, especially among immunocompromised individuals, necessitates careful and in-depth safety studies. The traditional probiotic safety evaluation methods investigate targeted phenotypic traits, such as virulence factors and antibiotic resistance. However, the rapid innovation in omics technologies has offered an impactful means to ultimately sequence and unknot safety-related genes or their gene products at preliminary levels. Further validating the genome features using an array of phenotypic tests would provide an absolute realization of gene expression dynamics. For safety studies in animal models, the in vivo toxicity evaluation guidelines of chemicals proposed by the Organization for Economic Co-operation and Development (OECD) have been meticulously adopted in probiotic research. Future research should also focus on coupling genome-scale safety analysis and establishing a link to its transcriptome, proteome, or metabolome for a fine selection of safe probiotic strains. Considering the studies published over the years, it can be inferred that the safety of probiotics is strain-host-dose-specific. Taken together, an amalgamation of in silico, in vitro, and in vivo approaches are necessary for a fine scale selection of risk-free probiotic strain for use in human applications.PMID:37039078 | DOI:10.1080/10408398.2023.2197066

Future Microbiol. 2023 Apr 11. doi: 10.2217/fmb-2022-0261. Online ahead of print.NO ABSTRACTPMID:37039024 | DOI:10.2217/fmb-2022-0261

Mol Nutr Food Res. 2023 Apr 11:e2200620. doi: 10.1002/mnfr.202200620. Online ahead of print.ABSTRACTSCOPE: Effective strategies for tailoring dietary advice to individuals are urgently needed. We investigate the effectiveness of personalised nutrition advice delivered using a metabotype framework in improving dietary quality and metabolic health biomarkers compared to population-level advice.MATERIALS AND RESULTS: A 12-week parallel randomised controlled trial was performed with 107 healthy adults. Individuals in the personalised group were classified into metabotypes using four marker (triacylglycerol, HDL-cholesterol, total cholesterol and glucose) and received dietary advice from decision tree algorithms containing metabotypes characteristics and individual traits. Individuals in the control group receiving generic dietary advice based on national guidelines. The personalised approach resulted in higher dietary quality assessed by the Alternate Mediterranean Diet Score (effect size [95% CI], 0.77 [0.07, 1.48], 12% versus 3% increase) and significantly lower concentrations of triacylglycerol (-0.17 [-0.28, -0.06] log10 mmol/L), total cholesterol (-0.42 [-0.74, -0.10] mmol/L), LDL-cholesterol (-0.34, [-0.60, -0.09] mmol/L) and lower triacylglycerol-glucose index (-0.40, [-0.67, -0.13]). Sixteen phosphatidylcholines and six lysophosphatidylcholines, predominately with chain lengths of 30-36 carbons were lower in the personalised group.CONCLUSIONS: Personalised nutrition advice delivered using the metabotype framework is effective to improve dietary quality, which could result in reduced CVD risk, and metabolic heath biomarkers. This article is protected by copyright. All rights reserved.PMID:37038841 | DOI:10.1002/mnfr.202200620

Curr Drug Metab. 2023 Apr 6. doi: 10.2174/1389200224666230406114012. Online ahead of print.ABSTRACTBACKGROUND: Polygonatum sibiricum polysaccharide (PSP) can improve insulin resistance and inhibit oxidative stress. However, the detailed anti-diabetic mechanism of PSP is still poorly defined.METHODS: In this study, the anti-diabetic, anti-inflammatory and anti-oxidative effects of PSP were evaluated on a type 2 diabetes mellitus (T2DM) rat model. Furthermore, we investigated the changes in gut microbiota and serum metabolites in T2DM rats after PSP treatment through 16S rRNA sequencing and untargeted metabolomics analyses.RESULTS: Our results showed that PSP exhibited significant anti-diabetic, anti-inflammatory and anti-oxidative effects on T2DM model rats. In addition, 16S rRNA sequencing showed that PSP treatment decreased the Firmicutes/Bacteroidetes ratio in the gut. At the genus level, PSP treatment increased the relative abundances of Blautia, Adlercreutzia, Akkermansia and Parabacteroides while decreasing Prevotella, Megamonas funiformis and Escherichia. Untargeted metabolomics analysis revealed that PSP treatment could affect 20 metabolites, including hexanoylglycine, (±)5(6)-DiHET, ecgonine, L-cysteine-S-sulfate, epitestosterone, (±)12(13)-DiHOME, glutathione, L-ornithine, D-mannose 6-phosphate, L-fucose, L-tryptophan, L-kynurenine, serotonin, melatonin, 3-hydroxyanthranilic acid, xylitol, UDP-D-glucuronate, hydroxyproline, 4-guanidinobutyric acid, D-proline in T2DM model rats, these metabolites are associated with arginine and proline metabolism, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, pentose and glucuronate interconversions, glutathione metabolism, arginine biosynthesis, ascorbate and aldarate metabolism pathways. Spearman correlation analysis results showed that the modulatory effects of PSP on the arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism pathways were related to the regulation of Prevotella, Megamonas funiformis, Escherichia, Blautia and Adlercreutzia.CONCLUSION: Our research revealed the therapeutic, anti-inflammatory and anti-oxidative effects of PSP on T2DM. The mechanisms of PSP on T2DM are associated with improving the dysbiosis of gut microbiota and regulating arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism in serum.PMID:37038712 | DOI:10.2174/1389200224666230406114012

Hemasphere. 2023 Apr 5;7(4):e858. doi: 10.1097/HS9.0000000000000858. eCollection 2023 Apr.ABSTRACTEarly fever after chimeric antigen receptor T-cell (CAR-T) therapy can reflect both an infection or cytokine release syndrome (CRS). Identifying early infections in the setting of CRS and neutropenia represents an unresolved clinical challenge. In this retrospective observational analysis, early fever events (day 0-30) were characterized as infection versus CRS in 62 patients treated with standard-of-care CD19.CAR-T for relapsed/refractory B-cell non-Hodgkin lymphoma. Routine serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], procalcitonin [PCT]) were recorded daily. Exploratory plasma proteomics were performed longitudinally in 52 patients using a multiplex proximity extension assay (Olink proteomics). Compared with the CRSonly cohort, we noted increased event-day IL-6 (median 2243 versus 64 pg/mL, P = 0.03) and particularly high PCT levels (median 1.6 versus 0.3 µg/L, P < 0.0001) in the patients that developed severe infections. For PCT, an optimal discriminatory threshold of 1.5 µg/L was established (area under the receiver operating characteristic curve [AUCROC] = 0.78). Next, we incorporated day-of-fever PCT levels with the patient-individual CAR-HEMATOTOX score. In a multicenter validation cohort (n = 125), we confirmed the discriminatory capacity of this so-called HT10 score for early infections at first fever (AUCROC = 0.87, P < 0.0001, sens. 86%, spec. 86%). Additionally, Olink proteomics revealed pronounced immune dysregulation and endothelial dysfunction in patients with severe infections as evidenced by an increased ANGPT2/1 ratio and an altered CD40/CD40L-axis. In conclusion, the high discriminatory capacity of the HT10 score for infections highlights the advantage of dynamic risk assessment and supports the incorporation of PCT into routine inflammatory panels. Candidate markers from Olink proteomics may further refine risk-stratification. If validated prospectively, the score will enable risk-adapted decisions on antibiotic use.PMID:37038465 | PMC:PMC10082278 | DOI:10.1097/HS9.0000000000000858

Cell Rep. 2023 Apr 10:112299. doi: 10.1016/j.celrep.2023.112299. Online ahead of print.ABSTRACTUnderstanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled an ancillary investigation of the gut microbiome, varying exposure to microgravity (flight) relative to ground controls in the context of previously shown bone mineral density (BMD) loss that was observed in these flight groups. We demonstrate elevated abundance of Lactobacillus murinus and Dorea sp. during microgravity exposure relative to ground control through whole-genome sequencing and 16S rRNA analyses. Specific functionally assigned gene clusters of L. murinus and Dorea sp. capable of producing metabolites, lactic acid, leucine/isoleucine, and glutathione are enriched. These metabolites are elevated in the microgravity-exposed host serum as shown by liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomic analysis. Along with BMD loss, ELISA reveals increases in osteocalcin and reductions in tartrate-resistant acid phosphatase 5b signifying additional loss of bone homeostasis in flight.PMID:37080202 | DOI:10.1016/j.celrep.2023.112299

BMC Plant Biol. 2023 Apr 10;23(1):190. doi: 10.1186/s12870-023-04195-x.ABSTRACTBACKGROUND: Waxy corn has a short growth cycle and high multiple cropping index. However, after being planted in early spring, late autumn and winter, it is susceptible to low temperature (LT), which reduces the emergence rate and yield. Therefore, it is important to analyze the response mechanism of waxy corn under LT stress.RESULTS: All phenotype indexes of waxy corn inbred lines N28 were significantly higher than waxy corn inbred lines N67 under LT. With the increase of LT stress time, all physiological indexes showed an upward trend in N28 and N67. Differentially expressed genes (DEGs) 16,017 and 14,435 were identified in N28 and N67 compared with nongerminated control under LT germination, respectively, and differential metabolites 127 and 93 were detected in N28 and N67, respectively. In addition, the expression level of some genes involved in plant hormones and mitogen activated protein kinase (MAPK) signaling pathways was significantly up-regulated in N28. Compared with N67, flavonoid metabolites were also significantly enriched in N28 under LT germination.CONCLUSION: Under LT stress, the inbred lines N28 was significantly higher than the inbred lines N67 in the phenotypic and physiological indices of cold resistance. Compared with N67, the expression levels of some genes involved in the plant hormones and MAPK pathways were significantly up-regulated in N28, and flavonoid metabolites were also significantly enriched in N28 under LT stress. These genes and metabolites may help N28 to improve cold resistance and may be as potential target genes for cold resistance breeding in waxy corn.PMID:37038118 | DOI:10.1186/s12870-023-04195-x

BMC Plant Biol. 2023 Apr 10;23(1):192. doi: 10.1186/s12870-023-04209-8.ABSTRACTBACKGROUND: As an important plant source of food and edible oils, pecans are rich in metabolites. Few studies have focused on metabolites involved in pecan seed germination at different temperatures.RESULTS: In our study, we germinated pecan seeds at different temperatures and found that, the germination rate and water content were highest at 30°C. It was found that the radicle of pecan seeds could sense seed coat cracking by observing the microstructure and cell ultra-structure of the seeds at the early stage of germination. We compared the metabolomes of seeds at different temperatures with different germination processes. A total of 349 metabolites were identified, including 138 primary metabolites and 211 secondary metabolites. KEGG enrichment analysis indicated that the differential metabolites were mainly enriched in the metabolic pathways, amino acid synthesis pathways and ABC transporters. Using weighted gene co-expression network analysis (WGCNA), three modules of closely related metabolites were identified. In the brown module, most of hub metabolites were amino substances, whereas in the blue module, many hub metabolites were sugars.CONCLUSIONS: Amino acids and carbohydrates play an important role in pecan seed germination. Differential metaboliteanalysis showed that 30°C was the temperature at which metabolites differed most significantly. This study provides useful information for further research on the seedling establishment of pecan seeds.PMID:37038116 | DOI:10.1186/s12870-023-04209-8

Adv Sci (Weinh). 2023 Apr 10:e2207454. doi: 10.1002/advs.202207454. Online ahead of print.ABSTRACTPulmonary fibrosis (PF) is a heterogeneous disease with a poor prognosis. Therefore, identifying additional therapeutic modalities is required to improve outcome. However, the lack of biomarkers of disease progression hampers the preclinical to clinical translational process. Here, this work assesses and identifies progressive alterations in pulmonary function, transcriptomics, and metabolomics in the mouse lung at 7, 14, 21, and 28 days after a single dose of oropharyngeal bleomycin. By integrating multi-omics data, this work identifies two central gene subnetworks associated with multiple critical pathological changes in transcriptomics and metabolomics as well as pulmonary function. This work presents a multi-omics-based framework to establish a translational link between the bleomycin-induced PF model in mice and human idiopathic pulmonary fibrosis to identify druggable targets and test therapeutic candidates. This work also indicates peripheral cannabinoid receptor 1 (CB1 R) antagonism as a rational therapeutic target for clinical translation in PF. Mouse Lung Fibrosis Atlas can be accessed freely at https://niaaa.nih.gov/mouselungfibrosisatlas.PMID:37038090 | DOI:10.1002/advs.202207454

Anal Sci. 2023 Apr 10. doi: 10.1007/s44211-023-00334-4. Online ahead of print.ABSTRACTThe quantitative analysis of near-infrared spectroscopy in traditional Chinese medicine has still deficiencies in the selection of the measured indexes. Then Paeoniae Radix Alba is one of the famous "Eight Flavors of Zhejiang" herbs, however, it lacks the pharmacodynamic support, and cannot reflect the quality of Paeoniae Radix Alba accurately and reasonably. In this study, the spectrum-effect relationship of the anti-inflammatory activity of Paeoniae Radix Alba was established. Then based on the obtained bioactive component groups, the genetic algorithm, back propagation neural network, was combined with near-infrared spectroscopy to establish calibration models for the content of the bioactive components of Paeoniae Radix Alba. Finally, three bioactive components, paeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, and benzoyl paeoniflorin, were successfully obtained. Their near-infrared spectroscopy content models were also established separately, and the validation sets results showed the coefficient of determination (R2 > 0.85), indicating that good calibration statistics were obtained for the prediction of key pharmacodynamic components. As a result, an integrated analytical method of spectrum-effect relationship combined with near-infrared spectroscopy and deep learning algorithm was first proposed to assess and control the quality of traditional Chinese medicine, which is the future development trend for the rapid inspection of traditional Chinese medicine.PMID:37037970 | DOI:10.1007/s44211-023-00334-4

Mol Psychiatry. 2023 Apr 10. doi: 10.1038/s41380-023-02051-w. Online ahead of print.ABSTRACTThe discovery of prenatal and neonatal molecular biomarkers has the potential to yield insights into autism spectrum disorder (ASD) and facilitate early diagnosis. We characterized metabolomic profiles in ASD using plasma samples collected in the Norwegian Autism Birth Cohort from mothers at weeks 17-21 gestation (maternal mid-gestation, MMG, n = 408) and from children on the day of birth (cord blood, CB, n = 418). We analyzed associations using sex-stratified adjusted logistic regression models with Bayesian analyses. Chemical enrichment analyses (ChemRICH) were performed to determine altered chemical clusters. We also employed machine learning algorithms to assess the utility of metabolomics as ASD biomarkers. We identified ASD associations with a variety of chemical compounds including arachidonic acid, glutamate, and glutamine, and metabolite clusters including hydroxy eicospentaenoic acids, phosphatidylcholines, and ceramides in MMG and CB plasma that are consistent with inflammation, disruption of membrane integrity, and impaired neurotransmission and neurotoxicity. Girls with ASD have disruption of ether/non-ether phospholipid balance in the MMG plasma that is similar to that found in other neurodevelopmental disorders. ASD boys in the CB analyses had the highest number of dysregulated chemical clusters. Machine learning classifiers distinguished ASD cases from controls with area under the receiver operating characteristic (AUROC) values ranging from 0.710 to 0.853. Predictive performance was better in CB analyses than in MMG. These findings may provide new insights into the sex-specific differences in ASD and have implications for discovery of biomarkers that may enable early detection and intervention.PMID:37037873 | DOI:10.1038/s41380-023-02051-w

Phytother Res. 2023 Apr 10. doi: 10.1002/ptr.7827. Online ahead of print.ABSTRACTDiabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg-1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg-1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of β-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.PMID:37037513 | DOI:10.1002/ptr.7827

Bioresour Technol. 2023 Apr 8:129041. doi: 10.1016/j.biortech.2023.129041. Online ahead of print.ABSTRACTThe microalgae Haematococcus pluvialis is a commercial source of natural astaxanthin. However, mature cells develop rigid three-layer wall structures and a repulsive odor. This study applied a liquid static fermentation system to screen hydrolyzing microorganisms for cell wall hydrolysis. Baijiu jiuqu and Gutian hongqu were found to have promising potential for application. The fermentation using 2% baijiu jiuqu and 2% glucose for pre-activation achieved comparable recovery of carotenoids to homogenizer disruption methods and produced stable fragrance which may be attributed to ethyl octanoate, hexyl formate, and phenethyl butyrate, as revealed by gas chromatography-mass spectrometry analysis. The abundance of astaxanthin molecules was slightly affected by fermentation with fold change < 2, while molecules with higher fold change (>10) were mainly carbohydrates, lipids, and steroids proving the safety of the fermentation. This study provides a new scheme for the biorefining of Haematococcus. pluvialis, potentially contributing to the industrial production of natural astaxanthin.PMID:37037338 | DOI:10.1016/j.biortech.2023.129041