PubMed

Orphanet J Rare Dis. 2024 Dec 19;19(1):466. doi: 10.1186/s13023-024-03449-7.ABSTRACTBACKGROUND: Bile acid synthesis defects (BASDs) can be severely disabling involving the liver and nervous system, potentially due to elevated levels of toxic C27-bile acid intermediates. Cholic acid (CA) supplementation is hypothesized to decrease bile acid production, stimulate bile secretion and -flow, and slowing down disease progression. This systematic review assesses the clinical and biochemical effectiveness, and safety of CA in BASDs patients.METHODS: A systematic review of MEDLINE, Embase and clinical trial registries (ClinicalTrials.gov, ICTRP registry) using controlled MeSH- and Emtree terms.RESULTS: From 526 articles 70 publications were deemed eligible for inclusion based on title and abstract. 14 publications were included after full-text assessment comprising case reports and -series with 1-35 patients (162 patients in total) receiving 1 week to 16,5 years of CA treatment. All presented data on effectiveness, 8 studies also presented data on safety. The included population concerned patients with Zellweger spectrum disorders (n = 73), 3β-Hydroxy-Δ5-C27-steroid oxidoreductase deficiency (n = 62), cerebrotendinous xanthomatosis (n = 22), Δ4-3-oxosteroid 5β-reductase deficiency (n = 13), and α-methylacyl-CoA racemase deficiency (n = 3). Main outcomes concerned liver disease (12 studies), general physical examinations, biochemical outcomes, and safety (9 studies), and fat-soluble vitamin absorption (7 studies). The overall risk of bias score was considered to be critical (1 study), serious (4 studies), and moderate (9 studies). Major issues were missing data (10 studies), generalized data (8 studies), and no wash-out between treatments (4 studies).CONCLUSION: More controlled studies are required as the available data is insufficient to draw definite conclusions on the effectiveness and safety of CA treatment in BASD patients. Establishing an independent international disease registry could better utilize existing real-world data.PMID:39702264 | DOI:10.1186/s13023-024-03449-7

BMC Public Health. 2024 Dec 19;24(1):3545. doi: 10.1186/s12889-024-21119-y.ABSTRACTBACKGROUND: Reproductive effects of chronic exposure to nickel (Ni), including sperm quality, have been a matter of debate given that published studies yielded contrasting results. We have, therefore, planned to systematically search and analyze medical literature with the aim to ascertain the association of exposure to nickel with the sperm quality in humans.MATERIALS AND METHODS: We systematically searched Pubmed, Scopus and Embase for studies reporting the association of Ni with the sperm quality in humans with no time or language limits and used PRISMA to report the findings. The risk of bias was assessed using JBI critical appraisal checklist and SIGN tool. Because the reported effects were no coherent, meta-analysis was not possible.RESULTS: All included studies were observational and planned to test the effect of a group of trace elements, but not Ni alone. We identified and included 19 studies from 23 publications, published from 12 countries, which assessed sperm quality, sperm DNA damage and sperm metabolome. Ni was quantified in blood, semen plasma, spermatozoa and urine. Sixteen included cross-sectional studies were of acceptable quality, whereas three more case-control reports were of poor quality. Multivariate models were reported in only eight studies. Overall, studies were inconsistent in the direction of effect, when elevated Ni was not associated with the outcome (N = 8 studies), or some association was present (N = 11 studies). In the latter, 9 studies yielded elevated risk and 2 studies exhibited protective effect. Only one report was in an occupationally exposed population with some association with tail defects, but present in both welders and controls.CONCLUSIONS: Existing evidence from the studies in humans is inconsistent and does not confirm a clear adverse effect of higher Ni concentrations in blood, urine or semen on the sperm quality. Robust methodology must be a key issue in the future studies. Studies with more powerful evidence, such as cohort or experimental reports are needed.PMID:39702049 | DOI:10.1186/s12889-024-21119-y

BMC Plant Biol. 2024 Dec 19;24(1):1210. doi: 10.1186/s12870-024-05933-5.ABSTRACTBACKGROUND: Magnolia officinalis (M. officinalis) thrives in temperate, elevated regions, and its desiccated bark comprises medicinal monolignol. Both abiotic and biotic factors can influence the pharmacodynamic compounds of M. officinalis, which display a variety of capabilities. It was the goal of this study to find the main bioclimatic factors that impact the amount of helpful compounds in M. officinalis and to show how these bioclimatic factors influence the metabolic pathways of magnolol and honokiol through actions on transcripts and molecules. We assessed the amounts of medicinal compounds in M. officinalis from Baoxing (BX), Nanjiang (NJ), Xuanhan (XH), and Beichuan (BC) in Sichuan Province. After that, the bioclimatic factors were gathered and put together that affected the growth and used the transcriptome and metabolome to label the M. officinalis data. The associated metabolic pathways were analyzed based on significant alterations in bioclimatic factors.RESULTS: Temperature and precipitation influence the accumulation of bioactive compounds in M. officinalis, as well as the metabolism of monolignol, amino acids, flavonoids, α-linolenic acid, and arachidonic acids. Moreover, temperature was negatively related to the mounts of phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), and cinnamoyl-CoA reductase (CCR) in the monolignol biosynthetic pathway, as well as to the amounts of cinnamyl alcohol and 4-coumaryl alcohol that were made.CONCLUSIONS: Moderate temperatures and appropriate precipitation enhanced the metabolism of monolignols in M. officinalis, ascribed to elevated levels of effective enzyme that correlated with the temperature and precipitation modulation of PAL, 4CL, and CCR activity. Furthermore, this study discovered that cinnamonyl alcohol and 4-coumaryl alcohol were critical precursors for the production of magnolol and honokiol, indicating potential strategies for improving M. officinalis' pharmacodynamic characteristics.PMID:39702009 | DOI:10.1186/s12870-024-05933-5

BMC Plant Biol. 2024 Dec 19;24(1):1195. doi: 10.1186/s12870-024-05914-8.ABSTRACTBACKGROUND: Poa pratensis is a predominant cool-season turfgrass utilized in urban landscaping and ecological management. It is extensively employed in turf construction and in the regulation of ecological environments. However, it is susceptible to powdery mildew, a prevalent disease in humid regions. Currently, the primary control measure for powdery mildew involves the application of pesticides, a practice that is both costly and environmentally detrimental. Developing superior disease-resistant cultivars represents a more cost-effective and sustainable strategy for managing turfgrass diseases. Furthermore, an in-depth investigation into the response mechanisms of P. pratensis to powdery mildew infection could significantly advance research on the identification of disease resistance genes and the molecular breeding of resistant varieties.RESULTS: In this study, we first assessed the disease incidence across various disease-resistant P. pratensis cultivars and subsequently examined alterations in their in vivo redox states. We employed isobaric tags for relative and absolute quantification (iTRAQ) proteomics alongside non-targeted metabolomics to elucidate the response mechanisms of P. pratensis to powdery mildew invasion. A comprehensive analysis of the shared KEGG pathways among differentially abundant proteins (DAPs) and differentially enriched metabolites (DEMs) led to the identification of four common KEGG pathways. Notably, the phenylpropanoid biosynthesis pathway, enriched in both examined P. pratensis cultivars, was selected for further investigation. This analysis indicated that lignin biosynthesis plays a crucial role in the response of P. pratensis to powdery mildew infection.CONCLUSIONS: The findings of this study enhance our understanding of the mechanisms underlying powdery mildew resistance in P. pratensis and serve as a valuable reference for the selection of powdery mildew-resistant cultivars, as well as for the identification and application of associated disease resistance genes.CLINICAL TRIAL NUMBER: Not applicable.PMID:39701986 | DOI:10.1186/s12870-024-05914-8

Neurotherapeutics. 2024 Dec 19:e00504. doi: 10.1016/j.neurot.2024.e00504. Online ahead of print.ABSTRACTAneurysmal subarachnoid hemorrhage (aSAH) results in a complex systemic response that is critical to the pathophysiology of late complications and has important effects on outcomes. Omics techniques have expanded our investigational scope and depth into this phenomenon. In particular, metabolomics-the study of small molecules, such as blood products, carbohydrates, amino acids, and lipids-can provide a snapshot of dynamic subcellular processes and thus broaden our understanding of molecular-level pathologic changes that lead to the systemic response after aSAH. Lipids are especially important due to their abundance in the circulating blood and numerous physiological roles. They are comprised of a wide variety of subspecies and are critical for cellular energy metabolism, the integrity of the blood-brain barrier, the formation of cell membranes, and intercellular signaling including neuroinflammation and ferroptosis. In this review, metabolomic and lipidomic pathways associated with aSAH are summarized, centering on key metabolites from each metabolomic domain.PMID:39701893 | DOI:10.1016/j.neurot.2024.e00504

J Appl Microbiol. 2024 Dec 19:lxae304. doi: 10.1093/jambio/lxae304. Online ahead of print.ABSTRACTAIMS: Glutamate wastewater poses a great environmental challenge to the monosodium glutamate production industry. However, its treatment solution is rich in crude protein, which has the potential to be developed as a new protein source for animal feed.METHODS AND RESULTS: Given that the fermentation process generates functionally different metabolites, this study innovatively utilized two strains of feed microorganisms, Aspergillus niger and Candida tropicalis, to perform solid-state fermentation of glutamate wastewater treatment solution. The aim was to investigate and analyze the metabolite profiles during fermentation. The significant differences in metabolite profiles between the samples were determined using correlation analysis, principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), variable importance in projection (VIP) analysis, Kyoto Encyclopaedia of Genomes (KEGG), and Human Metabolome Data Bank (HMDB) analysis. These variations were mainly manifested in essential feed components, such as amino acids, peptides, and their analogues. These included Ile-Pro-Asn, Pro-Gly-Val, alanylvaline, histidylisoleucine, Lys-Leu-Tyr, Ile-Arg, glycyl-leucine, leucyl-lysine, N-palmitoyl histidine, alanylisoleucine, L-glutamate, N-methylisoleucine, lsoleucylproline, DL-m-tyrosine, lsoleucyl-threonine, phenylalanine amide, carboxyethyllysine, N6-acetyl-L-lysine, citrulline, N-alpha-acetyl-L-lysine, N(6)-methyllysine, and L-aspartate-semialdehyde.CONCLUSIONS: This study investigates the metabolite profiles of glutamate wastewater treatment solutions after co-fermentation with Aspergillus niger and Candida tropicalis using solid-state fermentation. These findings provide a new strategy for efficiently utilizing glutamate wastewater treatment solutions.PMID:39701822 | DOI:10.1093/jambio/lxae304

J Appl Microbiol. 2024 Dec 19:lxae307. doi: 10.1093/jambio/lxae307. Online ahead of print.ABSTRACTAIMS: Potato common scab (CS), caused by pathogenic Streptomyces, is a devastating disease affecting potato crops worldwide. Antagonistic microorganisms have been used as biological control agents to inhibit Streptomyces scabies and reduce the use of synthetic pesticides. However, identifying beneficial microorganisms for controlling CS remain undetermined.METHODS AND RESULTS: Strain LS01 was isolated from the geocaulosphere soils of healthy potato tubers. In vitro and pot experiments demonstrated that strain LS01 significantly inhibited the mycelial growth and sporulation of S. scabies, thereby reducing the severity of CS. Sequencing of the 16S rRNA of LS01 indicated that the strain belonged to the species Bacillus safensis. Whole-genome sequencing, metabolomic analysis with LC-MS, and UHPLC/Q-TOF-MS analyses indicated that hygromycin B and plantazolicin may be the active secondary metabolites by which B. safensis LS01 inhibites S. scabies.CONCLUSIONS: B. safensis LS01 is a potential biocontrol agent for CS, with its secondary metabolites exerting effective inhibitory effects.PMID:39701816 | DOI:10.1093/jambio/lxae307

Zhongguo Zhong Yao Za Zhi. 2024 Nov;49(21):5888-5897. doi: 10.19540/j.cnki.cjcmm.20240718.301.ABSTRACTThis study aimed to investigate the toxicity differences of the ethyl acetate fraction of Euphorbiae Pekinensis Radix before and after vinegar processing and explore the detoxification mechanism of vinegar processing using non-targeted metabolomics. The changes in terpenoid components in the ethyl acetate fraction before and after vinegar processing were analyzed using UFLC-Q-TOF-MS. Normal rats were orally administered the raw and vinegar-processed ethyl acetate fractions of Euphorbia Pekinensis Radix. The toxicity differences in ethyl acetate fractions of Euphorbia Pekinensis Radix before and after vinegar processing were evaluated by pathological morphology, serum liver and kidney function, oxidative damage, and inflammatory injury indicators, and apoptosis factors. Serum metabolomics technology was utilized to identify changes in endogenous metabolites. Principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were employed to identify differential metabolites and metabolic pathways related to the detoxification of vinegar-processed Euphorbia Pekinensis Radix. The content of terpenoid components in the ethyl acetate fraction of Euphorbia Pekinensis Radix significantly decreased after vinegar processing. Histopathological sections and various indicators revealed that both the raw and vinegar-processed ethyl acetate fractions of Euphorbia Pekinensis Radix could induce toxicity in the liver, stomach, and intestine, with a reduction after vinegar processing. The toxicity was associated with oxidative damage, inflammatory injury, and apoptosis. A total of 13 differential metabolites and 5 main metabolic pathways related to Euphorbia Pekinensis Radix toxicity were identified by serum metabolomics. PCA and PLS-DA score plots indicated that both the raw and vinegar-processed ethyl acetate fractions disrupted the endogenous metabolic profiles in rats, mainly concentrating on lipid metabolism, primary bile acid biosynthesis, and arachidonic acid metabolism, with vinegar processing alleviating these metabolic disruptions. Therefore, the ethyl acetate fraction of Euphorbia Pekinensis Radix possesses liver, stomach, and intestinal toxicity, and vinegar processing reduces its toxicity by decreasing the content of terpenoid components. The detoxification mechanism may be related to alleviating oxidative damage, inflammatory injury, apoptosis, and improving lipid metabolism.PMID:39701798 | DOI:10.19540/j.cnki.cjcmm.20240718.301

Zhongguo Zhong Yao Za Zhi. 2024 Oct;49(19):5335-5342. doi: 10.19540/j.cnki.cjcmm.20240712.706.ABSTRACTThe gas chromatography-mass spectrometer(GC-MS) metabolomics method was used to investigate the anti-radiation effect of Yiguan Decoction water extract on mice and explore its related pathways and mechanisms of action. Healthy SPF male mice from Kunming were randomly assigned to six groups: blank group, model group, positive drug group, and high-dose, medium-dose, and low-dose groups of Yiguan Decoction, with ten mice in each group. Mice were prophylactically dosed for six days, and ~(60)Co γ ray with 5 Gy was used to establish a radiation mouse model. Changes in mouse body weight and peripheral blood within 14 days after radiation injury were observed, and exhaled breath from mice on the third day after radiation injury was collected. Mouse serum on the 14th day after radiation injury was collected, and GC-MS technology was applied to analyze the exhaled breath and serum of each group of mice, explore the differential metabolites and changes in content in exhaled breath and serum of mice under the anti-radiation effect of Yiguan Decoction. The metabolomics analysis of exhaled breath suggested that there were 15 differential metabolites in the exhaled breath of mice that were related to radiation injury, including hexane, ethyl acetate, hexanal, acetic acid, ethylbenzene, O-xylene, 1-hexanol, styrene, decane, octanal, mesitylene, D-limonene, acetophenone, nonanal, and naphthalene. The results of serum metabolomics analysis showed that 26 differential metabolites in mouse serum were related to radiation injury, including glycol, lactic acid, L-alanine, 3-hydroxybutyric acid, L-valine, glycerol, serine, and L-threonine. By constructing a metabolic network pathway related to the anti-radiation effect of Yiguan Decoction, three metabolic pathways were found to be associated with the anti-radiation effect of Yiguan Decoction, including linoleic acid metabolism, biosynthesis of phenylalanine, tyrosine, and tryptophan, and phenylalanine metabolism. The results indicated that Yiguan Decoction had a certain preventive and therapeutic effect on radiation injury in mice, and the mechanism of radiation injury was preliminarily explored, laying a foundation for the research on the mechanism of Yiguan Decoction against radiation.PMID:39701772 | DOI:10.19540/j.cnki.cjcmm.20240712.706

Zhongguo Zhong Yao Za Zhi. 2024 Oct;49(19):5181-5192. doi: 10.19540/j.cnki.cjcmm.20240710.301.ABSTRACTThis study aims to compare the effects and mechanisms of the standard decoction and formula granules of Paeoniae Radix Rubra in regulating the metabolism in the rat model of heat toxin and blood stasis. SD rats were randomized into control, model, standard decoction, and formula granules groups. After 14 days of administration, the rats in the latter three groups were subjected to subcutaneous injection with carrageenan and intraperitoneal injection with bacterial lipopolysaccharide for the modeling of heat toxin and blood stasis. The anal temperature, coagulation indexes, platelet aggregation(PAG), serum levels of thromboxane B_2(TXB_2), 6-ketone-prostaglondin F1α(6-keto-PGF1α), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), von Willebrand factor(vWF), endothelial nitric oxide synthase(eNOS), and endothelin-1(ET-1) were measured. The metabolites in rat serum were identified by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis was performed to screen the differential metabolites, which were then subjected to the KEGG pathway enrichment analysis. The results showed that the standard decoction and formula granules of Paeoniae Radix Rubra improved the state of model rats by lowering the body temperature, inhibiting inflammation, reducing PAG, delaying coagulation, and regulating the vascular function. The metabolomics analysis screened out 15 and 65 differential metabolites in the standard decoction and formula granules groups, respectively, compared with the model group. The enrichment analysis of the differential metabolites showed that the standard decoction of Paeoniae Radix Rubra exerted effects by affecting four key metabolic pathways: α-linolenic acid metabolism, primary bile acid biosynthesis, linoleic acid metabolism, and phenylalanine metabolism. The formula granules of Paeoniae Radix Rubra exerted effects by affecting four key metabolic pathways: α-linolenic acid metabolism, citrate cycle(tricarboxylic acid cycle), purine metabolism, and glyoxylic acid and dicarboxylic acid metabolism. This study indicated that the standard decoction and formula granules of Paeoniae Radix Rubra had similar effects on the syndrome of heat toxin and blood stasis and both of them regulated α-linolenic acid catabolism, which provided a scientific basis for the clinical application of the formula granules of Paeoniae Radix Rubra.PMID:39701756 | DOI:10.19540/j.cnki.cjcmm.20240710.301

Zhongguo Zhong Yao Za Zhi. 2024 Oct;49(20):5555-5565. doi: 10.19540/j.cnki.cjcmm.20240611.701.ABSTRACTThis study aims to elucidate the mechanism of Huangqin Decoction(HQD) in treating ulcerative colitis(UC) by investigating the relationship between tryptophan metabolism and intestinal barriers. In the in vivo experiments, 3% dextran sulfate sodium(DSS) was used to induce a mouse model of acute colitis, with mesalazine as a positive control. The therapeutic effect of HQD on mice with UC was evaluated according to body weight, disease activity index(DAI), colon length, and pathological changes. Targeted metabolomics was used to detect the concentration of tryptophan and its metabolites in mouse feces. Western blot and RT-qPCR techniques were used to assess the expression levels of colonic aryl hydrocarbon receptor(AhR), myosin light chain kinase(MLCK), myo-sin light chain(MLC), and p-MLC. Serum FITC-dextran concentration, bacterial culture of mesenteric lymph nodes and spleen, as well as fluorescence probe in situ hybridization technique were used to evaluate intestinal epithelial permeability. Alcian blue and nuclear fast red staining, Western blot, and RT-qPCR techniques were used to detect the expression of mucin secreted by the mouse's intestinal epithelial goblet cells. Transmission electron microscopy was utilized to observe the connections of the mouse's intestinal epithelial cells. Immunofluorescence, Western blot, and RT-qPCR techniques were used to assess the expression of tight junction proteins in the mouse's intestinal epithelium. In the in vitro experiments, lipopolysaccharide(LPS) was used to induce intestinal epithelial barrier injury model in Caco2 cells, and AhR siRNA was used to further clarify the mechanism of HQD in activating AhR to improve intestinal barrier function. The results demonstrated that HQD effectively alleviated symptoms and pathological changes in the colon of DSS-induced mice with colitis. Treatment with HQD could regulate tryptophan metabolism in the feces of mice with colitis, activate AhR, and improve the intestinal epithelial barrier. Additionally, the results of the in vitro experiments confirmed that HQD could restore the expression of tight junction proteins in the intestinal epithelium of colitis cells by activating AhR to regulate the MLCK/p-MLC signaling pathway.PMID:39701738 | DOI:10.19540/j.cnki.cjcmm.20240611.701

Zhongguo Zhong Yao Za Zhi. 2024 Oct;49(20):5516-5527. doi: 10.19540/j.cnki.cjcmm.20240702.401.ABSTRACTThis study aims to explore the therapeutic effect of Yuzhi Zhixue Granules on polycystic ovary syndrome(PCOS) in rats and explain the underlying mechanism by metabolomics. Rats were randomized into normal, model, low-, medium-, and high-dose(0.5, 1.5, and 4.5 g·kg~(-1)·d~(-1)) Yuzhi Zhixue Granules, and positive control(metformin, 0.2 g·kg~(-1)·d~(-1)) groups. The rats in other groups except the normal group were administrated with 1 mg·kg~(-1)·d~(-1) letrozole and fed with a high-sugar and high-fat diet for the modeling of PCOS. After 40 days of modeling, the normal and model groups received distilled water and letrozole+distilled water, respectively, and other groups received letrozole and corresponding drugs, once a day for 50 days. The oral glucose tolerance test(OGTT) was carried out and enzyme-linked immunosorbent assay(ELISA) was conducted to detect insulin release, and the radioimmunoassay was employed to measure the serum levels of follicle-stimulating hormone(FSH), luteinizing hormone(LH), estradiol(E_2), and testosterone(T). The serum levels of high density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol(LDL-C), and triglyceride(TG) were determined by an automatic biochemical analyzer. The pathological changes in the ovary were observed by hematoxylin-eosin(HE) staining. The protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), and their phosphorylated forms in the ovary were determined by Western blot. Ultra-high performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was employed to study the fecal and serum metabolites in the rat model of PCOS. The results showed that compared with the model group, drug administration repaired the impaired glucose tolerance, enhanced the insulin sensitivity, elevated the serum levels of HDL-C and E_2, lowered the serum levels of TG and T, ameliorated the pathological changes in the ovarian tissue, and up-regulated the protein levels of p-PI3K and p-Akt in the ovarian tissue. A total of 46 differential metabolites and 10 metabolic pathways in the fecal samples were screened out, which were mainly related to the biosynthesis of unsaturated fatty acids and tyrosine metabolism. In terms of the serum metabolism, 34 differential metabolites and 15 metabolic pathways were screened out, mainly related to the biosynthesis of unsaturated fatty acids and aminoacyl-tRNA. In conclusion, Yuzhi Zhixue Granules can alleviate the disorders of glucose, lipids, and sex hormones and improve the ovarian status in the rat model of PCOS by regulating the serum and fecal metabolism and activating the PI3K/Akt pathway.PMID:39701735 | DOI:10.19540/j.cnki.cjcmm.20240702.401

Zhongguo Zhong Yao Za Zhi. 2024 Oct;49(20):5441-5450. doi: 10.19540/j.cnki.cjcmm.20240714.102.ABSTRACTTo deeply understand the chemical components and functional differences of the rhizomes from different Coptis species, this study employed widely targeted metabolomics for the metabolic profiling of C. chinensis, C. deltoidea, and C. teeta. A total of 658 metabolites including alkaloids, lipids, flavonoids, and phenolic acids were identified. The result of principal component analysis(PCA) revealed significant differences of the metabolites among different Coptis species. C. chinensis had a richer variety of total alkaloids than C. deltoidea and C. teeta. According to the results of orthogonal partial least squares-discriminant analysis(OPLS-DA) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, the differential metabolites of the three species were significantly enriched in the secondary metabolic pathways dominated by the biosynthesis of isoquinolines. The cluster analysis of shared differential metabolites showed that alkaloids accounted for the largest proportion. The content of total alkaloids in C. chinensis was significantly higher than that in C. teeta and C. deltoidea. S-Plot was employed to predict the metabolic markers and the key differential secondary metabolites related to the pharmacological effects of Coptidis Rhizoma were analyzed. The results showcased that the relative content of berberine and palmatine in C. chinensis was significantly higher than that in C. teeta and C. deltoidea, and thus the two components could serve as biomarkers for metabolic differences among the three Coptis species. This study provided basic data for the overall evaluation and breeding of Coptis resources, laying a foundation for further quality control and precise medication of Coptidis Rhizoma.PMID:39701727 | DOI:10.19540/j.cnki.cjcmm.20240714.102

Zhongguo Zhong Yao Za Zhi. 2024 Oct;49(20):5422-5432. doi: 10.19540/j.cnki.cjcmm.20240713.102.ABSTRACTLaser capture microdissection(LCM) combined with gas chromatography-mass spectrometry(GC-MS) was employed to investigate the distribution of volatile compound in the secretory cavities of different tissues(cortex, phloem, xylem, and pith) in different rhizome sections of wild Atractylodes lancea. The same method was used to study the metabolic characteristics of the volatile compounds in the secretory cavities of different rhizome tissues of A. lancea transplanted for 1-3 years. In the rhizome of wild A. lancea, the accumulation of volatile compounds such as atractylodin, atractylon, and atractylenolide Ⅰ in the secretory cavities of the cortex was significantly higher in the middle sections(sections 2-6) than that at the two ends(sections 1 and 7). In the rhizome of A. lancea transplanted for 1 year, the volatile compounds such as atractylodin, atractylon, atractylenolideⅠ, and atractylenolide Ⅱ were mainly accumulated in the secretory cavities of the cortex. In the rhizome of A. lancea transplanted for 2 years, the tested volatile compounds except selina-4(14),7(11)-dien-8-one were enriched in the secretory cavities of all the tissues. In the rhizome of A. lancea transplanted for 3 years, atractylon, hinesol, and β-eudesmol were mainly accumulated in the secretory cavities of the pith. The overall accumulation of volatile compounds in each rhizome tissue of cultivated A. lancea increased with the increase in transplanting years. Non-targeted metabolomics and absolute quantification confirmed that the volatile compounds were mainly accumulated in the secretory cavities of the cortex in the middle rhizome sections of wild A. lancea. The accumulation in the rhizome of cultivated A. lancea presented a trend from cortex, phloem, xylem to pith over time. In this study, the spatio-temporal distribution map of volatile compounds in the rhizome of A. lancea was established.PMID:39701725 | DOI:10.19540/j.cnki.cjcmm.20240713.102

Zhongguo Zhong Yao Za Zhi. 2024 Nov;49(22):5998-6007. doi: 10.19540/j.cnki.cjcmm.20240508.401.ABSTRACTPlant polysaccharides are effective components that widely present in traditional Chinese medicine(TCM), exhibiting rich biological activities. However, as most plant polysaccharides cannot be directly absorbed and utilized by the human digestive system, it is now believed that their mode of action mainly involves interaction with intestinal microbiota, leading to the production of functional small molecules. The efficacy of Astragalus polysaccharide(APS) is extensive, including weight loss, improvement of fatty liver, reduction of blood lipids, and enhancement of insulin sensitivity, which may also be related to the regulation of intestinal microbiota. Adipose tissue senescence is an important characteristic of the physiological aging process in the body, often occurring prior to the aging of other important organs. Its main features include the accumulation of senescent cells and exacerbation of inflammation within the tissue. Therefore, to explore the potential protective effects of APS on aging, the improvement of adipose tissue aging phenotype in naturally aging mice was observed using APS, and combined with metagenomic metabolomics, corresponding microbial metabolic functional molecules were identified. Furthermore, functional tests in cell aging models were conducted. The results showed that APS significantly improved the adipocyte aging characteristics of naturally aging mice: specifically reducing aging-induced adipocyte hypertrophy; decreasing the protein expression of aging markers cyclin-dependent kinase inhibitor p21(P21) and multiple tumor suppressor 1(P16); lowering the tissue inflammation reaction. Metagenomic metabolomic analysis of serum from mice in each group revealed that APS significantly increased the content of indole-3-lactic acid(ILA) in naturally aging mice. Further in vitro studies showed that ILA could improve the aging of 3T3-L1 mouse embryonic fibroblasts induced by bleomycin, reduce the protein expression of the aging marker P21, alleviate inflammation, and enhance the ability of preadipocytes to mature. Therefore, APS had the efficacy of protecting naturally aging mice, and its action may be related to the increase in the intestinal microbiota metabolite ILA. This study suggested that TCM may serve as an important entry point for explaining the mechanism of action of TCM by regulating intestinal microbiota and their functional metabolites.PMID:39701698 | DOI:10.19540/j.cnki.cjcmm.20240508.401

Zhongguo Zhong Yao Za Zhi. 2024 Nov;49(22):5988-5997. doi: 10.19540/j.cnki.cjcmm.20240611.708.ABSTRACTParabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.PMID:39701697 | DOI:10.19540/j.cnki.cjcmm.20240611.708

Zhongguo Zhong Yao Za Zhi. 2024 Sep;49(18):4913-4924. doi: 10.19540/j.cnki.cjcmm.20240615.101.ABSTRACTTo explore the difference in metabolism and transcription between seeds experiencing space flight and ground seeds after morphological post ripening, this study utilized ginseng seeds experiencing space flight and ground seeds as materials. Metabolomics and transcriptomics analyses were conducted using ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS) and high-throughput transcriptome sequencing(RNA-seq) technologies, so as to identify differential terpenoid metabolites, differential endogenous hormones, and differentially expressed genes. The results showed that through metabolomics analysis, a total of 22 differential terpenoid metabolites were identified in the experimental and control groups, including chikusetsusaponin FK_7, ginsenoside F_2, ginseno-side K, majoroside R_1, ginsenoside Re_5, 12-hydroxyabietic acid, etc; through transcriptomics analysis, 15 differential terpenoid metabolism-related differentially expressed genes were identified in the experimental and control groups, including FCase, AACT, PMK, etc, and these genes were integrated into the pathway based on the MEP and MVA. At the same time, genes related to the seed germination process such as LEC2, PIPK, PUF, REC, QUD, and PIR were screened. In the detection of endogenous hormones, a total of 17 differential hormone metabolites were obtained, including IAA, CK, JA, ABA, GA, and SA. Among them, the content of CK increased in the SP group, while the content of GA and SA decreased in the SP group. Genes related to CK, GA, and SA were also screened. This study laid the foundation for further exploration of the biosynthesis of terpenoid metabolites in ginseng seeds and the key endogenous hormones and enzyme genes involved in the seed germination process, and it provided a reference for the application of space flight mutagenesis technology in ginseng.PMID:39701674 | DOI:10.19540/j.cnki.cjcmm.20240615.101

J Dairy Sci. 2024 Dec 17:S0022-0302(24)01390-0. doi: 10.3168/jds.2024-25784. Online ahead of print.ABSTRACTOne-carbon metabolism (OCM) is a series of connected pathways involving the methionine-folate cycles, transsulfuration, polyamine synthesis, nucleotide synthesis, free-radical scavenging, and energy metabolism. These pathways functionally depend upon amino acids (methionine, glycine, and serine), vitamins (folate, B2, B6, and B12), and minerals (sulfur, cobalt, and zinc). Growing bodies of research indicate that in beef cattle, physiological stage, nutritional plane, diet, species (Bos taurus vs. indicus), rumen protected vs. not, individual vs. combination supplementation and method of delivery all affect the efficacy of one-carbon metabolite supplementation. Infusion studies showed that supplementing methionine to growing steers improved N retention and altered hepatic activity of methionine synthase; however, only supplementing methionine without folate decreased folate concentrations in circulation. When heifers were supplemented with methionine, choline, folate, and B12 for the first 63 d of gestation, metabolomic analysis revealed increasing OCM analytes to the heifer, but a buffering effect to the fetus with minimal changes seen in hepatic metabolite abundance. Methionine supplementation to heifers during the periconceptual period increased circulating methionine but shifted fetal hepatic metabolism toward the transsulfuration pathway. Periconceptual methionine supplementation to cows increased gain and total-tract digestibility in calves post-weaning. In vitro supplementation of choline to beef cattle embryos results in calves of increased birth and weaning weight. Overall, these data demonstrate that OCM is altered in those cattle receiving one-carbon metabolites, and that a metabolic programming response is elicited in offspring receiving supplements in vitro or during early gestation. Research should be considered to maximize efficiency of beef cattle production at all stages by identifying limiting metabolites or enzymes to maximize efficiency of OCM in beef cattle, as well as to understand the concerted effects of multiple one-carbon metabolites to balance the stoichiometry of the pathway.PMID:39701525 | DOI:10.3168/jds.2024-25784

Contemp Clin Trials. 2024 Dec 17:107776. doi: 10.1016/j.cct.2024.107776. Online ahead of print.ABSTRACTINTRODUCTION: Effective spontaneous preterm birth (sPTB) prevention is an urgent unmet clinical need. Vaginal depletion of Lactobacillus crispatus is linked to sPTB. This trial will investigate impact of an oral Lactobacillus spp. probiotic product containing an L. crispatus strain with other Lactobacilli spp., on the maternal vaginal and gut microbiome in pregnancies high-risk for sPTB.METHODS: A double-blind, placebo-controlled, randomised trial will be performed at the National Maternity Hospital Dublin, Ireland. Inclusion criteria are women with history of sPTB or mid-trimester loss, cervical surgery (cone biopsy or two previous large-loop-excision-of-transformation-zone) or uterine anomaly. The intervention is oral supplementation for twelve weeks with probiotic or identical placebo. The probiotic will contains: ◦ 4 billion CFU Lactobacillus crispatus Lbv 88(2x109CFU/Capsule) ◦ 4 billion CFU Lactobacillus rhamnosus Lbv 96(2x109CFU/Capsule) ◦ 0.8 billion CFU Lactobacillus jensenii Lbv 116(0.4x109CFU/Capsule) ◦ 1.2 billion CFU Lactobacillus gasseri Lbv 150(0.6x109CFU/Capsule) Investigators and participants will be blinded to assignment.RESULTS: The primary outcome is detectable L. crispatus in the vaginal microbiome after twelve weeks of treatment, measured using high-throughput DNA sequencing. A total of 126 women are required to detect a 25 % increase in detectable L. crispatus. Secondary outcomes include impact of intervention on the gut microbiome and metabolome, rate of sPTB and mid-trimester loss, neonatal outcomes and maternal morbidity.CONCLUSIONS: This randomised trial will investigate ability of an oral probiotic containing L. crispatus to increase its abundance in the vaginal microbiome, both directly by horizontal transfer and indirectly via microbiome and metabolome of the gut.PMID:39701375 | DOI:10.1016/j.cct.2024.107776

Int J Biol Macromol. 2024 Dec 17:138831. doi: 10.1016/j.ijbiomac.2024.138831. Online ahead of print.ABSTRACTHexokinase 2 (HK2) plays a vital role in mitochondrial homeostasis; however, the molecular mechanisms underlying its involvement in high-concentrate diet-induced damage in the ruminal epithelium of dairy cows are poorly understood. This study aimed to explore the regulatory role of HK2 in mitochondrial function and responses to inflammation in the rumen of dairy cows fed a high-concentrate diet. Our results showed that, compared with a low-concentrate (LC) diet, feeding a high-concentrate (HC) diet increased oxidative stress and reduced relative antioxidant gene expression levels and enzyme activities in the ruminal epithelium. Furthermore, the expression of genes related to mitochondrial biosynthesis and structure decreased in the HC group, concomitant with nuclear oligomerization domain (NOD)-like receptor 3 (NLRP3) signaling pathway activation, which compromised normal rumen epithelium function. Meanwhile, transcription results showed the same trend in HK2-knockout bovine rumen epithelial cells (HK2KO BRECs) related to wild-type (WT) BRECs. Notably, the knockout of HK2 aggravated mitochondrial dysfunction, resulting in the impairment of mitochondrial morphology and quality, a reduction in mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (MPTP) opening, increased reactive oxygen species (ROS) generation, and decreased expression of antioxidant genes. These changes led to upregulating genes and proteins in the NLRP3 pathway and activating proinflammatory response. In addition, metabolomic results showed that knockout HK2 altered the glycerophospholipid metabolic pathway. This study provides new strategies for mitigating high-concentrate diet-induced injury in the ruminal epithelium of dairy cows.PMID:39701238 | DOI:10.1016/j.ijbiomac.2024.138831