PubMed

Gut. 2023 Nov;72(11):e4. doi: 10.1136/gutjnl-2022-328708corr1.NO ABSTRACTPMID:37802539 | DOI:10.1136/gutjnl-2022-328708corr1

J Biol Chem. 2023 Oct 4:105319. doi: 10.1016/j.jbc.2023.105319. Online ahead of print.ABSTRACTMis-folding of the prion protein (PrP) is known to cause neurodegenerative disease, however the native function of this protein remains poorly defined. PrP has been linked with many cellular functions, including cellular proliferation and senescence. It is also known to influence epidermal growth factor receptor (EGFR) signalling, a pathway that is itself linked with both cell growth and senescence. Adult neural stem cells (NSCs) persist at low levels in the brain throughout life and retain the ability to proliferate and differentiate into new neural lineage cells. Knock-out (KO) of PrP has previously been shown to reduce NSC proliferative capacity. We used PrP KO and wild type (WT) NSCs from adult mouse brain to examine the influence of PrP on cellular senescence, EGFR signalling, and the downstream cellular processes. PrP KO NSCs showed decreased cell proliferation and increased senescence in in vitro cultures. Expression of EGFR was decreased in PrP KO NSCs compared with WT NSCs and additional supplementation of EGF was sufficient to reduce senescence. RNAseq analysis confirmed that significant changes were occurring at the mRNA level within the EGFR signalling pathway and these were associated with reduced expression of mitochondrial components and correspondingly reduced mitochondrial function. Metabolomic analysis of cellular energy pathways showed that blockages were occurring at critical sites for production of energy and biomass, including catabolism of pyruvate. We conclude that, in the absence of PrP, NSC growth pathways are downregulated as a consequence of insufficient energy and growth intermediates.PMID:37802314 | DOI:10.1016/j.jbc.2023.105319

Adv Nutr. 2023 Oct 4:S2161-8313(23)01388-1. doi: 10.1016/j.advnut.2023.09.015. Online ahead of print.ABSTRACTHuman milk (HM) contains macronutrients, micronutrients and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched Medline, EMBASE, Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980-2022 on HM components and anthropometry through 2 years of age among term-born infants. From 9,992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9,980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent amongst the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only five studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n=6773 dyads), compared to 13 (n=2,640 dyads) for HMOs, and 12 (n=1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, interleukin-6 (IL-6) demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture human milk intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth.PMID:37802214 | DOI:10.1016/j.advnut.2023.09.015

Metabolism. 2023 Oct 4:155695. doi: 10.1016/j.metabol.2023.155695. Online ahead of print.ABSTRACTBACKGROUND: Gestational diabetes (GDM) is a distinctive form of diabetes that first presents in pregnancy. While most women return to normoglycemia after delivery, they are nearly ten times more likely to develop type 2 diabetes than women with uncomplicated pregnancies. Current prevention strategies remain limited due to our incomplete understanding of the early underpinnings of progression.AIM: To comprehensively characterize the postpartum profiles of women shortly after a GDM pregnancy and identify key mechanisms responsible for the progression to overt type 2 diabetes using multi-dimensional approaches.METHODS: We conducted a nested case-control study of 200 women from the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy (SWIFT) to examine biochemical, proteomic, metabolomic, and lipidomic profiles at 6-9 weeks postpartum (baseline) after a GDM pregnancy. At baseline and annually up to two years, SWIFT administered research 2-h 75-g oral glucose tolerance tests. Women who developed incident type 2 diabetes within four years of delivery (incident case group, n = 100) were pair-matched by age, race, and pre-pregnancy body mass index to those who remained free of diabetes for at least 8 years (control group, n = 100). Correlation analyses were used to assess and integrate relationships across profiling platforms.RESULTS: At baseline, all 200 women were free of diabetes. The case group was more likely to present with dysglycemia (e.g., impaired fasting glucose levels, glucose tolerance, or both). We also detected differences between groups across all omic platforms. Notably, protein profiles revealed an underlying inflammatory response with perturbations in protease inhibitors, coagulation components, extracellular matrix components, and lipoproteins, whereas metabolite and lipid profiles implicated disturbances in amino acids and triglycerides at individual and class levels with future progression. We identified significant correlations between profile features and fasting plasma insulin levels, but not with fasting glucose levels. Additionally, specific cross-omic relationships, particularly among proteins and lipids, were accentuated or activated in the case group but not the control group.CONCLUSIONS: Overall, we applied orthogonal, complementary profiling techniques to uncover an inflammatory response linked to elevated triglyceride levels shortly after a GDM pregnancy, which is more pronounced in women who progress to overt diabetes.PMID:37802200 | DOI:10.1016/j.metabol.2023.155695

Biochim Biophys Acta Mol Basis Dis. 2023 Oct 4:166910. doi: 10.1016/j.bbadis.2023.166910. Online ahead of print.ABSTRACTMetabolomics has proven great potential to unravel the molecular basis of diseases. However, most attempts aimed at identifying reliable metabolomics-based biomarkers for diagnosis, prediction, and prognosis of diseases have repeatedly failed because of inconsistent results and unsatisfactory replication in independent cohorts. This review article explores the possible causes behind this reproducibility crisis, with special focus on the role that inter-individual variability factors play in modulating the susceptibility to disease development. Furthermore, we provide future perspectives on the applicability of metabolomics in biomedical research and its translatability into clinical practice.PMID:37802155 | DOI:10.1016/j.bbadis.2023.166910

Cell Metab. 2023 Sep 27:S1550-4131(23)00337-6. doi: 10.1016/j.cmet.2023.09.002. Online ahead of print.ABSTRACTCold-induced thermogenesis (CIT) is widely studied as a potential avenue to treat obesity, but a thorough understanding of the metabolic changes driving CIT is lacking. Here, we present a comprehensive and quantitative analysis of the metabolic response to acute cold exposure, leveraging metabolomic profiling and minimally perturbative isotope tracing studies in unanesthetized mice. During cold exposure, brown adipose tissue (BAT) primarily fueled the tricarboxylic acid (TCA) cycle with fat in fasted mice and glucose in fed mice, underscoring BAT's metabolic flexibility. BAT minimally used branched-chain amino acids or ketones, which were instead avidly consumed by muscle during cold exposure. Surprisingly, isotopic labeling analyses revealed that BAT uses glucose largely for TCA anaplerosis via pyruvate carboxylation. Finally, we find that cold-induced hepatic gluconeogenesis is critical for CIT during fasting, demonstrating a key functional role for glucose metabolism. Together, these findings provide a detailed map of the metabolic rewiring driving acute CIT.PMID:37802078 | DOI:10.1016/j.cmet.2023.09.002

Phytomedicine. 2023 Sep 27;121:155115. doi: 10.1016/j.phymed.2023.155115. Online ahead of print.ABSTRACTBACKGROUND: Evodia Rutaecarpa-processed Coptidis Rhizoma (ECR) is a traditional Chinese medicine for the treatment of ulcerative colitis (UC) in China. However, the mechanisms underlying the ECR processing are not elucidated.PURPOSE: Coptidis Rhizoma (CR) regulates the gut microbiota in the treatment of gastrointestinal diseases. This study explored the mechanism of action of ECR before and after processing in UC in view of the regulation of gut microecology.STUDY DESIGN: A preclinical experimental investigation was performed using a mouse model of UC to examine the regulatory effect of ECR and its mechanisms through gut microbiota analysis and metabolomic assays.METHODS: Mice received 4% dextran sulfate sodium to establish a UC model and treated with ECR and CR. Colonic histopathology and inflammatory changes were observed. Gut microbiota was analyzed using 16 s rRNA sequencing. Transplants of Lactobacillus reuteri were used to explore the correlation between ECR processing and the gut microbiota. The expression of mucin-2, Lgr5, and PCNA in colonic epithelial cells was measured using immunofluorescence. Wnt3a and β-catenin levels were detected by western blotting. The metabolites in the colon tissue were analyzed using a targeted energy metabolomic assay. The effect of energy metabolite α-ketoglutarate (α-KG) on L. reuteri growth and UC were verified in mice.RESULTS: ECR improved the effects on UC in mice compared to CR, including alleviating colonic injury and inflammation, and modulating gut microbiota by increasing L. reuteri level. L. reuteri dose-dependently alleviated colonic injury, increased mucin-2 level, and promoted colonic epithelial regeneration by increasing Lgr5 and PCNA expression. This was consistent with the results before and after ECR processing. L. reuteri promoted epithelial regeneration by upregulating Wnt/β-catenin pathway. Moreover, ECR increased metabolites levels (especially α-KG) to promote energy metabolism in the colon tissue compared to CR. α-KG treatment increased L. reuteri level and alleviated mucosal damage in UC mice. It promoted L. reuteri growth by increasing the energy metabolic status by enhancing α-KG dehydrogenase activity.CONCLUSION: ECR processing improves the therapeutic effects of UC via the α-KG-L. reuteri-epithelial regeneration axis.PMID:37801896 | DOI:10.1016/j.phymed.2023.155115

Food Chem. 2023 Sep 30;435:137643. doi: 10.1016/j.foodchem.2023.137643. Online ahead of print.ABSTRACTGC × GC-ToF-MS is increasingly used to analyze complex food flavors due to its high resolution and sensitivity, but few studies have used the method to identify aroma components of bread. For the first time, this study combines GC × GC-ToF-MS and multivariate statistical methods to explore the effects of L. paracasei fermentation on bread flavor characteristics. A total of 1534 volatile organic compounds were identified, of which 447 were obtained by metabolome normalization. Based on the variable importance for the projection and p values, 82 different compounds were screened in L. paracasei bread compared with yeast bread, and the total relative content was 1.52 times higher than that of yeast bread. 2-Furancarboxaldehyde, 5-methyl-, pentanoic acid, 2-hydroxy-4-methyl-, ethyl ester, pyrazine, 2,5-dimethyl- and γ-terpinene are aroma-presenting substances specific to L. paracasei bread that could be potential identification compounds. This study provides a new techno-theoretical approach for the characterization and discrimination of LAB bread flavors.PMID:37801769 | DOI:10.1016/j.foodchem.2023.137643

Food Chem. 2023 Sep 23;435:137551. doi: 10.1016/j.foodchem.2023.137551. Online ahead of print.ABSTRACTBacterial blight caused by Xanthomonas arboricola pv. juglandis is a major obstacle to walnut production. EPS66A, derived from Streptomyces sp. strain HL-66, has various beneficial properties, including broad-spectrum microbe inhibition and plant disease resistance induction. To understand the effects of Xaj and EPS66A on walnut, a comprehensive analysis of the metabolome and transcriptome was conducted. While EPS66A did not directly inhibit Xaj on agar media, applying it at 200 μg/mL, 24 h after Xaj inoculation on walnut leaves, significantly reduced bacterial blight in a greenhouse. Additionally, EPS66A increased phenolic and flavonoid concentrations and enhanced enzymatic activities associated with resistance, such as catalase, superoxide dismutase, peroxidase, and phenylalanine ammonia lyase. Differential expression of eleven metabolites and fourteen genes related to flavonoid biosynthesis pathway was observed. Consequently, EPS66A application induced systemic resistance in walnuts, effectively preventing Xaj infection. This study provides insights into the flavonoid biosynthesis mechanism underlying EPS66A-induced resistance in walnuts.PMID:37801767 | DOI:10.1016/j.foodchem.2023.137551

BMC Plant Biol. 2023 Oct 6;23(1):466. doi: 10.1186/s12870-023-04494-3.ABSTRACTBACKGROUND: Chimonobambusa hejiangensis (C.hejiangensis) is a high-quality bamboo species native to China, known for its shoots that are a popular nutritional food. Three C.hejiangensis cultivars exhibit unique color variation in their shoot sheaths, however, the molecular mechanism behind this color change remains unclear.METHODS: We investigated flavonoid accumulation in the three bamboo cultivar sheaths using metabolomics and transcriptomics.RESULTS: UPLC-MS/MS identified 969 metabolites, with 187, 103, and 132 having differential accumulation in the yellow-sheath (YShe) vs. spot-sheath (SShe)/black-sheath (BShe) and SShe vs. BShe comparison groups. Flavonoids were the major metabolites that determined bamboo sheath color through differential accumulation of metabolites (DAMs) analysis. Additionally, there were 33 significantly differentially expressed flavonoid structural genes involved in the anthocyanin synthesis pathway based on transcriptome data. We conducted a KEGG analysis on DEGs and DAMs, revealing significant enrichment of phenylpropanoid and flavonoid biosynthetic pathways. Using gene co-expression network analysis, we identified nine structural genes and 29 transcription factors strongly linked to anthocyanin biosynthesis.CONCLUSION: We identified a comprehensive regulatory network for flavonoid biosynthesis which should improve our comprehension of the molecular mechanisms responsible for color variation and flavonoid biosynthesis in bamboo sheaths.PMID:37803268 | DOI:10.1186/s12870-023-04494-3

Methods Mol Biol. 2024;2719:181-197. doi: 10.1007/978-1-0716-3461-5_11.ABSTRACTAdvancements in high-throughput technologies, genomics, transcriptomics, and metabolomics play an important role in obtaining biological information about living organisms. The field of computational biology and bioinformatics has experienced significant growth with the advent of high-throughput sequencing technologies and other high-throughput techniques. The resulting large amounts of data present both opportunities and challenges for data analysis. Big data analysis has become essential for extracting meaningful insights from the massive amount of data. In this chapter, we provide an overview of the current status of big data analysis in computational biology and bioinformatics. We discuss the various aspects of big data analysis, including data acquisition, storage, processing, and analysis. We also highlight some of the challenges and opportunities of big data analysis in this area of research. Despite the challenges, big data analysis presents significant opportunities like development of efficient and fast computing algorithms for advancing our understanding of biological processes, identifying novel biomarkers for breeding research and developments, predicting disease, and identifying potential drug targets for drug development programs.PMID:37803119 | DOI:10.1007/978-1-0716-3461-5_11

Methods Mol Biol. 2024;2719:99-119. doi: 10.1007/978-1-0716-3461-5_6.ABSTRACTAdvanced technology innovations allow cost-effective, high-throughput profiling of biological systems. It enabled genome sequencing in days using advanced technologies (e.g., next-generation sequencing, microarrays, and mass spectrometry). Since technology has been developed, massive biological data (e.g., genomics, proteomics) has been produced cheaply, allowing the "big data" era to create new opportunities to solve medical and biological complications in many disciplines-preventive medicine, biology, Personalized Medicine, gene sequencing, healthcare, and industry. Computational biology and bioinformatics are interdisciplinary fields that develop and apply computational methods (e.g., analytical methods, mathematical modeling, and simulation) to analyze large collections of biological data, such as genetic sequences, cell populations, or protein samples, to make new predictions or discover new biology. Biological data storage, mining, and analysis have challenges because data is much more heterogeneous. In this study, the big data resources of genomics, proteomics, and metabolomics have been explored to solve biological problems using big data analysis approaches. The goal is to build a network of relationship-based gene-disease associations to prioritize phenotypes common to epilepsy and seizure disease. Through network analysis, The 10 seed genes, 22 associated genes, 132 microRNAs, and 38 transcription factors have been identified that have a direct effect on all forms of epilepsy and seizures. The majority of seed genes, according to the results of a functional analysis of seed genes, are involved in the acetylcholine-gated channel complex (10%) and the heterotrimeric G-protein complex (10%) pathways related to cellular components, followed by a role in the regulation of action potential (20%) and positive regulation of vascular endothelial growth factor production (20%) in Epilepsy and Seizures pathways related to biological processes. This study might provide insight into the workings of the disease and shows the importance of continued research into epilepsy and other conditions that can trigger seizure activity.PMID:37803114 | DOI:10.1007/978-1-0716-3461-5_6

Sci Rep. 2023 Oct 6;13(1):16846. doi: 10.1038/s41598-023-43964-4.ABSTRACTStudies have shown that high humidity is a condition that aggravates the pain of rheumatoid arthritis (RA), but the relevant mechanism is controversial. Currently, there is a lack of experimental animal studies on high humidity as an adverse factor related to the pathogenesis of RA. We used healthy SD rats and collagen-induced arthritis (CIA) rats to investigate the effects of high humidity on arthritis. Integrated metabolomics analyses of faeces and 16S rRNA sequencing of the faecal microbiota were performed to comprehensively assess the diversity of the faecal microbiota and metabolites in healthy and CIA rats. In this study, high humidity aggravated arthritis in CIA rats, which manifested as articular cartilage lesions, increased arthritis scores, and an increase in proinflammatory cytokines. High humidity had a certain effect on the articular cartilage extent, arthritis score and proinflammatory cytokines of healthy rats as well. Furthermore, high humidity caused significant changes in faecal microbes and metabolites in both healthy and CIA rats. 16S rRNA sequencing of faecal samples showed that high humidity increased the amount of inflammation-related bacteria in healthy and CIA rats. Faecal metabolomics results showed that high humidity significantly altered the level of faecal metabolites in healthy rats and CIA rats, and the changes in biological functions were mainly related to the inflammatory response and oxidative stress. Combined analysis showed that there was a strong correlation between the faecal microbiota and faecal metabolites. High humidity is an adverse factor for the onset and development of RA, and its mechanism is related to the inflammatory response and oxidative stress. However, the question of how high humidity impacts RA pathogenesis needs to be further investigated.PMID:37803075 | DOI:10.1038/s41598-023-43964-4

Sci Rep. 2023 Oct 6;13(1):16863. doi: 10.1038/s41598-023-43983-1.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) cells have a great demand for nutrients in the form of sugars, amino acids, and lipids. Particularly, amino acids are critical for cancer growth and, as intermediates, connect glucose, lipid and nucleotide metabolism. PDAC cells meet these requirements by upregulating selective amino acid transporters. Here we show that SLC38A5 (SN2/SNAT5), a neutral amino acid transporter is highly upregulated and functional in PDAC cells. Using CRISPR/Cas9-mediated knockout of SLC38A5, we show its tumor promoting role in an in vitro cell line model as well as in a subcutaneous xenograft mouse model. Using metabolomics and RNA sequencing, we show significant reduction in many amino acid substrates of SLC38A5 as well as OXPHOS inactivation in response to SLC38A5 deletion. Experimental validation demonstrates inhibition of mTORC1, glycolysis and mitochondrial respiration in KO cells, suggesting a serious metabolic crisis associated with SLC38A5 deletion. Since many SLC38A5 substrates are activators of mTORC1 as well as TCA cycle intermediates/precursors, we speculate amino acid insufficiency as a possible link between SLC38A5 deletion and inactivation of mTORC1, glycolysis and mitochondrial respiration, and the underlying mechanism for PDAC attenuation. Overall, we show that SLC38A5 promotes PDAC, thereby identifying a novel, hitherto unknown, therapeutic target for PDAC.PMID:37803043 | DOI:10.1038/s41598-023-43983-1

Nat Commun. 2023 Oct 6;14(1):6246. doi: 10.1038/s41467-023-41952-w.ABSTRACTCancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings.PMID:37803016 | DOI:10.1038/s41467-023-41952-w

Zhongguo Zhong Yao Za Zhi. 2023 Sep;48(17):4747-4760. doi: 10.19540/j.cnki.cjcmm.20230510.702.ABSTRACTIn this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.PMID:37802814 | DOI:10.19540/j.cnki.cjcmm.20230510.702

Zhongguo Zhong Yao Za Zhi. 2023 Sep;48(17):4711-4721. doi: 10.19540/j.cnki.cjcmm.20230512.401.ABSTRACTThis study aimed to investigate the protective effect and underlying mechanism of Mailuo Shutong Pills(MLST) on posterior limb swelling caused by femur fracture in rats. The rats were randomly divided into a sham operation group, a model group, a low-dose MLST group(1.8 g·kg~(-1)·d~(-1)), a high-dose MLST group(3.6 g·kg~(-1)·d~(-1)), and a positive drug group(60 mg·kg~(-1)·d~(-1) Maizhiling Tablets). The femur in the sham operation group was exposed and the wound was sutured, while the other four groups underwent mechanical damage to cause femur fracture. The rats were treated with corresponding drugs by gavage 7 days before modeling and 5 days after modeling, while those in the sham operation group and the model group were given an equivalent dose of distilled water by gavage. Hematoxylin-eosin(HE) staining was used to detect the pathological injury of the posterior limb muscle tissues in rats, and the degree of hind limb swelling was measured. The enzyme-linked immunosorbent assay(ELISA) kit was used to detect the expression levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in the serum of rats in each group. The activity of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and glutathione peroxidase(GSH-Px) in rat serum was also measured. Western blot was used to detect the protein expression levels of heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), and nuclear transcription factor E2-related factor 2(Nrf2) in rat posterior limb muscle tissues. The changes in the intestinal flora and intestinal metabolites in rats were detected by 16S rDNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), respectively, to explore the underlying mechanism of MLST in treating posterior limb swelling caused by femur fracture in rats. Compared with the model group, MLST significantly improved the degree of posterior limb swelling in rats, reduced the levels of serum inflammatory factors, and alleviated oxidative stress injury. The HE staining results showed that the inflammatory infiltration in the posterior limb muscle tissues of rats in the MLST groups was significantly improved. Western blot results showed that MLST significantly increased the protein expression of HO-1, NQO1, and Nrf2 in rat posterior limb muscle tissues compared with the model group. The 16S rDNA sequencing results showed that MLST improved the disorder of intestinal flora in rats after femur fracture. The UPLC-MS/MS results showed that MLST significantly affected the bile acid biosynthesis and metabolism pathway in the intestine after femur fracture, and the Spearman analysis confirmed that the metabolite deoxycholic acid involved in bile acid biosynthesis was positively correlated with the abundance of Turicibacter. The metabolite cholic acid was positively correlated with the abundance of Papilibacter, Staphylococcus, and Intestinimonas. The metabolite lithocholic acid was positively correlated with Papilibacter and Intestinimonas. The above results indicated that MLST could protect against the posterior limb swelling caused by femur fracture in rats. This protective effect may be achieved by improving the pathological injury of the posterior limb muscle, reducing the expression levels of inflammatory and oxidative stress-related factors in serum, reducing the oxidative injury of the posterior limb muscle, improving intestinal flora, and balancing the biosynthesis of bile acids in the intestine.PMID:37802810 | DOI:10.19540/j.cnki.cjcmm.20230512.401

Zhongguo Zhong Yao Za Zhi. 2023 Sep;48(17):4634-4646. doi: 10.19540/j.cnki.cjcmm.20230414.101.ABSTRACTDead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.PMID:37802802 | DOI:10.19540/j.cnki.cjcmm.20230414.101

Zhongguo Zhong Yao Za Zhi. 2023 Aug;48(15):4097-4105. doi: 10.19540/j.cnki.cjcmm.20230313.103.ABSTRACTTo explore the resource components and availability of different parts of Panax quinquefolium in Shandong province, the paper employed the non-targeted metabolomics technology based on ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) to analyze the metabolites and their metabolic pathways in the root, fibril, stem, and leaf of P. quinquefolium. The content of seven ginsenosides and polysaccharides in different parts was determined by high performance liquid chromatography(HPLC) and ultraviolet-visible spectrophotometry(UV-Vis). The results showed that the metabolites were mainly sugars, glycosides, organic acids, amino acids and their derivatives, terpenoids, etc. The total abundance of metabolites followed the trend of leaf > root > fibril > stem. Most of the differential metabolites were concentrated in phenylpropane biosynthesis, flavonoid biosynthesis, citric acid cycle, and amino acid biosynthesis. The leaf contained high levels of sugars, glycosides, amino acids and their derivatives, and flavonoids; the root was rich in terpenoids, volatile oils, vitamins, and lignin; the fibril contained rich organic acids; and the stem had high content of nucleotides and their derivatives. The content of ginsenosides Re and Rb_1 was significantly higher in the root; the content of ginsenosides Rg_1, Rg_2, Rd, F_(11), and polysaccharide was significantly higher in the leaf; and the content of ginsenoside Rb_2 was significantly higher in the stem. We analyzed the resource components and availability of different parts of P. quinquefolium, aiming to provide basic information for the comprehensive development and utilization of P. quinquefolium resources in Shandong province.PMID:37802777 | DOI:10.19540/j.cnki.cjcmm.20230313.103

Zhongguo Zhong Yao Za Zhi. 2023 Aug;48(15):4039-4045. doi: 10.19540/j.cnki.cjcmm.20230303.401.ABSTRACTThis study aimed to investigate the mechanism of Psoraleae Fructus in improving the learning and memory ability of APP/PS1 mice by serum metabolomics, screen the differential metabolites of Psoraleae Fructus on APP/PS1 mice, and reveal its influence on the metabolic pathway of APP/PS1 mice. Thirty 3-month-old APP/PS1 mice were randomly divided into a model group and a Psoraleae Fructus extract group, and another 15 C57BL/6 mice of the same age were assigned to the blank group. The learning and memory ability of mice was evaluated by the Morris water maze and novel object recognition tests, and metabolomics was used to analyze the metabolites in mouse serum. The results of the Morris water maze test showed that Psoraleae Fructus shortened the escape latency of APP/PS1 mice(P<0.01), and increased the number of platform crossing and residence time in the target quadrant(P<0.01). The results of the novel object recognition test showed that Psoraleae Fructus could improve the novel object recognition index of APP/PS1 mice(P<0.01). Eighteen differential metabolites in serum were screened out by metabolomics, among which the levels of arachidonic acid, tryptophan, and glycerophospholipid decreased after drug administration, while the levels of glutamyltyrosine increased after drug administration. The metabolic pathways involved included arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and glycerolipid metabolism. Therefore, Psoraleae Fructus can improve the learning and memory ability of APP/PS1 mice, and its mechanism may be related to the effects in promoting energy metabolism, reducing oxidative damage, protecting central nervous system, reducing neuroinflammation, and reducing Aβ deposition. This study is expected to provide references for Psoraleae Fructus in the treatment of Alzheimer's disease(AD) and further explain the mechanism of Psoraleae Fructus in the treatment of AD.PMID:37802771 | DOI:10.19540/j.cnki.cjcmm.20230303.401