PubMed

J Ethnopharmacol. 2024 Jun 5:118438. doi: 10.1016/j.jep.2024.118438. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear.AIM OF THE STUDY: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia.MATERIALS AND METHODS: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses.RESULTS: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of bile acid (BA) and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice.CONCLUSIONS: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.PMID:38848972 | DOI:10.1016/j.jep.2024.118438

Int J Biol Macromol. 2024 Jun 5:132938. doi: 10.1016/j.ijbiomac.2024.132938. Online ahead of print.ABSTRACTColored corn pericarp contains unusually high amounts of industrially valuable phytochemicals, such as anthocyanins, flavanols, flavonoids, and phenolic acids. Polyphenols were extracted in an aqueous solution and spray-dried to produce microencapsulates using four carrier materials, namely, maltodextrin (MD), gum arabic (GA), methylcellulose (MC), and skim milk powder (SMP) at three concentrations (1, 2, and 3 %, respectively). The encapsulates were evaluated for their polyphenolic contents using spectrophotometric techniques and HPLC analyses, and their antioxidant properties were evaluated using four different assays. The physicochemical properties of encapsulates were analyzed by measuring the zeta potential (ZP), particle size distribution, water solubility index (WSI), water absorption index (WAI), and color parameters. Structural and thermal properties were evaluated using Fourier transform infrared spectroscopy (FTIR), optical profilometry, and differential scanning calorimetry (DSC) analyses. Comparative analysis of structural characteristics, particle size distribution, zeta potential, WSI, WAI, and aw of the samples confirmed the successful formulation of encapsulates. The microencapsulates embedded with 1 % concentrations of MD, MC, GA, or SMP retained polyphenolic compounds and exhibited noteworthy antioxidant properties. The samples encapsulated with GA or MD (1 %) demonstrated superior physicochemical, color, and thermal properties. Comprehensive metabolomic analysis confirmed the presence of 38 phytochemicals in extracts validating the spray-drying process.PMID:38848831 | DOI:10.1016/j.ijbiomac.2024.132938

J Agric Food Chem. 2024 Jun 7. doi: 10.1021/acs.jafc.4c02956. Online ahead of print.ABSTRACTAlbino germplasms are prized tea plant mutants with yellow/white leaves. However, understanding of the albino mechanisms in non-Camellia sinensis tea species remains limited. This study elucidated the albino trait formation in Nanchuan Dachashu (C. nanchuanica), an arbor-type tea species, and its association with tea quality. The yellow-leaved albino individual NH1 exhibited abnormal chloroplast ultrastructure and reduced chlorophyll/carotenoid levels compared to green-leaved NL1. Integrating transcriptomics, metabolomics, yeast one-hybrid, and transgenic approaches identified the chlorophyll b reductase gene CsNYC1a as a key regulator, which was significantly up-regulated in NH1, and its overexpression in Arabidopsis recapitulated the albino phenotype. In yeast, histone CsH1.2 binds to the CsNYC1a promoter. These findings suggest that CsH1.2-CsNYC1a-mediated chlorophyll degradation may be a key mechanism underlying albino formation in Nanchuan Dachashu. In addition, as a germplasm with higher polyphenol-to-amino acid ratio than NL1, NH1 offers more possibilities for breeding and application.PMID:38848450 | DOI:10.1021/acs.jafc.4c02956

Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun 7. doi: 10.1007/s00210-024-03201-9. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD) is often accompanied by metabolic imbalance, and infliximab (IFX) can alleviate IBD symptoms, but its metabolic mechanisms remain unclear. To investigate the relationship between IBD, metabolism, and IFX, an acute and chronic ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) was established. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis. The results showed that IFX could alleviate colonic shortening and reduce colonic pathological damage in acute and chronic mouse colitis, improve acute and chronic UC, and ameliorate metabolic disturbances. Among the 104 elevated metabolites and 170 decreased metabolites, these metabolites mainly belonged to amino acids, glucose, and purines. The changes in these metabolites were mainly associated with drug metabolism-other enzymes, riboflavin metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phosphonate and phosphinate metabolism, and phenylalanine metabolism. In summary, this study provides a valuable approach to explore the metabolic mechanisms of IFX in treating acute and chronic UC from a metabolomics perspective.PMID:38847830 | DOI:10.1007/s00210-024-03201-9

Int J Surg. 2024 Jun 7. doi: 10.1097/JS9.0000000000001724. Online ahead of print.ABSTRACTBACKGROUND: The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC.METHODS: Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes we focus on.RESULTS: This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC (n=285), CP (n=342), and control (n=649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=-0.33; P=0.002 and SMD=-0.59; P<0.001, respectively) and a statistically significant β-diversity (P<0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that 4 genera were significantly increased in PDAC patients compared to HC (e.g., Escherichia-Shigella and Veillonella). CP patients had an increase in 4 genera (e.g., Escherichia-Shigella and Klebsiella) and a decrease in 8 genera (e.g., Coprococcus and Bifidobacterium) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients.CONCLUSIONS: Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.PMID:38847785 | DOI:10.1097/JS9.0000000000001724

J Agric Food Chem. 2024 Jun 7. doi: 10.1021/acs.jafc.4c02243. Online ahead of print.ABSTRACTLiver inflammation could be elicited by swainsonine in livestock, affecting the development of agriculture and animal husbandry. Our previous study showed an important role of bile acids (BAs) in swainsonine-induced hepatic inflammation. However, its pathogenesis, particularly the roles of a comprehensive profile of liver and serum metabolites and microbial-derived indole metabolites, has not been clarified. This study aimed to demonstrate the mechanisms linking the indole-producing bacteria and indole metabolites to swainsonine-induced hepatic inflammation by combining Targeted 500 metabolomics and quantitative analysis of indole metabolites. Swainsonine significantly disturbed the liver and serum metabolomes in mice. Genus Akkermansia alleviating inflammation and genus Lactobacillus producing indole metabolites were significantly declined. Indole acetic acid (IAA) was the only reduced aryl hydrocarbon receptor (AHR) ligand in this study. Analogously, some bacteria causing liver damage markedly increased. These findings suggested that indole-producing bacteria and indole metabolites may be potential triggers of swainsonine-induced hepatic inflammation.PMID:38847775 | DOI:10.1021/acs.jafc.4c02243

Curr Opin Crit Care. 2024 Jun 10. doi: 10.1097/MCC.0000000000001178. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Sepsis remains a leading global cause of morbidity and mortality, and despite decades of research, no effective therapies have emerged. The lack of progress in sepsis outcomes is related in part to the significant heterogeneity of sepsis populations. This review seeks to highlight recent literature regarding sepsis phenotypes and the potential for further research and therapeutic intervention.RECENT FINDINGS: Numerous recent studies have elucidated various phenotypes, subphenotypes, and endotypes in sepsis. Clinical parameters including vital sign trajectories and microbial factors, biomarker investigation, and genomic, transcriptomic, proteomic, and metabolomic studies have illustrated numerous differences in sepsis populations with implications for prediction, diagnosis, treatment, and prognosis of sepsis.SUMMARY: Sepsis therapies including care bundles, fluid resuscitation, and source control procedures may be better guided by validated phenotypes than universal application. Novel biomarkers may improve upon the sensitivity and specificity of existing markers and identify complications and sequelae of sepsis. Multiomics have demonstrated significant differences in sepsis populations, most notably expanding our understanding of immunosuppressed sepsis phenotypes. Despite progress, these findings may be limited by modest reproducibility and logistical barriers to clinical implementation. Further studies may translate recent findings into bedside care.PMID:38847501 | DOI:10.1097/MCC.0000000000001178

FASEB J. 2024 Jun 15;38(11):e23718. doi: 10.1096/fj.202400329R.ABSTRACTFemale carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female mdx mice and the potential of estrogen replacement therapy (using estradiol) to protect against functional and metabolic perturbations. We also investigated the effect of estrogen depletion, and replacement, on the skeletal muscle proteome through an untargeted proteomic approach with TMT-labelling. Our study confirms that loss of estrogen in female mdx mice reduces exercise capacity, tricarboxylic acid cycle intermediates, and citrate synthase activity but that these deficits are offset through estrogen replacement therapy. Furthermore, ovariectomy downregulated protein expression of RNA-binding motif factor 20 (Rbm20), a critical regulator of sarcomeric and muscle homeostasis gene splicing, which impacted pathways involving ribosomal and mitochondrial translation. Estrogen replacement modulated Rbm20 protein expression and promoted metabolic processes and the upregulation of proteins involved in mitochondrial dynamics and metabolism. Our data suggest that estrogen mitigates dystrophinopathic features in female mdx mice and that estrogen replacement may be a potential therapy for post-menopausal DMD carriers.PMID:38847487 | DOI:10.1096/fj.202400329R

Plant Cell Environ. 2024 Jun 7. doi: 10.1111/pce.14989. Online ahead of print.ABSTRACTPlants share their habitats with a multitude of different microbes. This close vicinity promoted the evolution of interorganismic interactions between plants and many different microorganisms that provide mutual growth benefits both to the plant and the microbial partner. The symbiosis of Arabidopsis thaliana with the beneficial root colonizing endophyte Serendipita indica represents a well-studied system. Colonization of Arabidopsis roots with S. indica promotes plant growth and stress tolerance of the host plant. However, until now, the molecular mechanism by which S. indica reprograms plant growth remains largely unknown. This study used comprehensive transcriptomics, metabolomics, reverse genetics, and life cell imaging to reveal the intricacies of auxin-related processes that affect root growth in the symbiosis between A. thaliana and S. indica. Our experiments revealed the sustained stimulation of auxin signalling in fungus infected Arabidopsis roots and disclosed the essential role of tightly controlled auxin conjugation in the plant-fungus interaction. It particularly highlighted the importance of two GRETCHEN HAGEN 3 (GH3) genes, GH3.5 and GH3.17, for the fungus infection-triggered stimulation of biomass production, thus broadening our knowledge about the function of GH3s in plants. Furthermore, we provide evidence for the transcriptional alteration of the PIN2 auxin transporter gene in roots of Arabidopsis seedlings infected with S. indica and demonstrate that this transcriptional adjustment affects auxin signalling in roots, which results in increased plant growth.PMID:38847336 | DOI:10.1111/pce.14989

Int J Oncol. 2024 Jul;65(1):73. doi: 10.3892/ijo.2024.5661. Epub 2024 Jun 7.ABSTRACTSeveral studies have indicated that the gut microbiome and tumor microbiota may affect tumors. Emerging metabolomics research illustrates the need to examine the variations in microbial metabolite composition between patients with cancer and healthy individuals. Microbial metabolites can impact the progression of tumors and the immune response by influencing a number of mechanisms, including modulation of the immune system, cancer or immune‑related signaling pathways, epigenetic modification of proteins and DNA damage. Microbial metabolites can also alleviate side effects and drug resistance during chemotherapy and immunotherapy, while effectively activating the immune system to exert tumor immunotherapy. Nevertheless, the impact of microbial metabolites on tumor immunity can be both beneficial and harmful, potentially influenced by the concentration of the metabolites or the specific cancer type. The present review summarizes the roles of various microbial metabolites in different solid tumors, alongside their influence on tumor immunity and treatment. Additionally, clinical trials evaluating the therapeutic effects of microbial metabolites or related microbes on patients with cancer have been listed. In summary, studying microbial metabolites, which play a crucial role in the interaction between the microbiota and tumors, could lead to the identification of new supplementary treatments for cancer. This has the potential to improve the effectiveness of cancer treatment and enhance patient prognosis.PMID:38847233 | DOI:10.3892/ijo.2024.5661

Food Chem X. 2024 May 7;22:101446. doi: 10.1016/j.fochx.2024.101446. eCollection 2024 Jun 30.ABSTRACTThe bitter and astringent taste and miscellaneous smell of vine tea prevent its further development. In this study, we used a processing technology that mimics yellow tea to improve the flavor of vine tea and revealed its internal reasons through metabolomics. Sensory evaluation showed the yellowing process for 6-12 h reduced the bitterness and astringency significantly, and enriched the aroma. The improvement of taste was mainly related to the down-regulation of anthocyanins (54.83-97.38%), the hydrolysis of gallated catechins (34.80-47.81%) and flavonol glycosides (18.56-44.96%), and the subsequent accumulation of d-glucose (33.68-78.04%) and gallic acid (220.96-252.09%). For aroma, increase of total volatile metabolite content (23.88-25.44%) and key compounds like geraniol (239.32-275.21%) induced the changes. These results identified the positive effects of yellowing process on improvements in vine tea flavor and the key compounds that contribute to these changes.PMID:38846795 | PMC:PMC11154209 | DOI:10.1016/j.fochx.2024.101446

Front Microbiol. 2024 May 23;15:1373077. doi: 10.3389/fmicb.2024.1373077. eCollection 2024.ABSTRACTINTRODUCTION: Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.METHODS: Mice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS).RESULTS: In this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).CONCLUSION: These results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.PMID:38846566 | PMC:PMC11153696 | DOI:10.3389/fmicb.2024.1373077

Front Microbiol. 2024 May 23;15:1391558. doi: 10.3389/fmicb.2024.1391558. eCollection 2024.ABSTRACTSanghuangprous vaninii is a medicinal macrofungus cultivated extensively in China. Both the mycelia and fruiting bodies of S. vaninii have remarkable therapeutic properties, but it remains unclear whether the mycelia may serve as a substitute for the fruiting bodies. Furthermore, S. vaninii is a perennial fungus with therapeutic components that vary significantly depending on the growing year of the fruiting bodies. Hence, it is critical to select an appropriate harvest stage for S. vaninii fruiting bodies for a specific purpose. With the aid of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), metabolomics based on ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS) was used to preliminarily determine 81 key active metabolites and 157 active pharmaceutical metabolites in S. vaninii responsible for resistance to the six major diseases. To evaluate the substitutability of the mycelia and fruiting bodies of S. vaninii and to select an appropriate harvest stage for the fruiting bodies of S. vaninii, we analyzed the metabolite differences, especially active metabolite differences, among the mycelia and fruiting bodies during three different harvest stages (1-year-old, 2-year-old, and 3-year-old). Moreover, we also determined the most prominent and crucial metabolites in each sample of S. vaninii. These results suggested that the mycelia show promise as a substitute for the fruiting bodies of S. vaninii and that extending the growth year does not necessarily lead to higher accumulation levels of active metabolites in the S. vaninii fruiting bodies. This study provided a theoretical basis for developing and using S. vaninii.PMID:38846565 | PMC:PMC11153664 | DOI:10.3389/fmicb.2024.1391558

Physiol Mol Biol Plants. 2024 May;30(5):807-822. doi: 10.1007/s12298-024-01462-5. Epub 2024 May 22.ABSTRACTPolyamines play an important role in growth and differentiation by regulating numerous physiological and biochemical processes at the cellular level. In addition to their roborative effect, their essential role in plant stress responses has been also reported. However, the positive effect may depend on the fine-tuning of polyamine metabolism, which influences the production of free radicals and/or signalling molecules. In the present study, 0.3 mM hydroponic putrescine treatment was tested in wheat, maize, and rice in order to reveal differences in their answers and highlight the relation of these with polyamine metabolism. In the case of wheat, the chlorophyll content and the actual quantum yield increased after putrescine treatment, and no remarkable changes were detected in the stress markers, polyamine contents, or polyamine metabolism-related gene expression. Although, in maize, the actual quantum yield decreased, and the root hydrogen peroxide content increased, no other negative effect was observed after putrescine treatment due to activation of polyamine oxidases at enzyme and gene expression levels. The results also demonstrated that after putrescine treatment, rice with a higher initial polyamine content, the balance of polyamine metabolism was disrupted and a significant amount of putrescine was accumulated, accompanied by a detrimental decrease in the level of higher polyamines. These initial differences and the putrescine-induced shift in polyamine metabolism together with the terminal catabolism or back-conversion-induced release of a substantial quantity of hydrogen peroxide could contribute to oxidative stress observed in rice.PMID:38846465 | PMC:PMC11150351 | DOI:10.1007/s12298-024-01462-5

Open Res Eur. 2024 Jan 29;3:140. doi: 10.12688/openreseurope.16514.2. eCollection 2023.ABSTRACTThe Bulgarian research landscape, presented mainly by the research institutes that are part of the Bulgarian Academy of Sciences and the Agricultural Academy, needs diversification to match the research and innovation potential of the other European Union (EU) countries. This article describes the establishment of the Center of Plant Systems Biology and Biotechnology (CPSBB), a new innovative type of independent research organization that is changing the research landscape in Bulgaria. Supported by the EU Commission, Bulgarian Government, and Plovdiv Municipality, CPSBB has quickly become the leading plant science institute in Bulgaria, creating knowledge in diverse fields such as bioinformatics, biotechnology, genetics and genomics, metabolomics, and systems biology. We outline the organizational structure of CPSBB, the development of its infrastructure, and its scientific productivity. Finally, we compare CPSBB with other similar research establishments in Europe and we conclude that such new types of institutes have a bright future in Bulgaria due to their operational flexibility, productivity, and connections with academia and industry.PMID:38846177 | PMC:PMC11153986 | DOI:10.12688/openreseurope.16514.2

Front Pharmacol. 2024 May 23;15:1402758. doi: 10.3389/fphar.2024.1402758. eCollection 2024.ABSTRACTBACKGROUND: This study aimed to explore the regulatory effect of anserine on HUVEC cell injury and thrombosis in deep venous thrombosis (DVT) rats, and to elucidate the underlying molecular mechanisms.METHODS: Non-targeted metabolomics data analyses were conducted using an ultra-performance liquid chromatography system Vanquish UHPLC and mass spectrometer to detect plasma metabolism profiles. The transcriptome sequencing and gene intervention experiments were performed to verify the regulatory effect. Further in vivo and in vitro experiments were performed. Enzyme-linked immunosorbent assay was used to detect the levels of P-selectin, E-selectin, and vWF, hematoxylin-eosin (HE) staining was performed to observe thrombotic and inflammatory cell infiltration, flow cytometry and TUNEL assays were performed to detect apoptosis, and qPCR and WB assays were conducted to determine the gene and protein expression.RESULTS: Anserine alleviated HUVECs injury, reduced adhesion molecule expression, and inflammation. It decreased P-selectin, E-selectin, vWF, THBD, TFPI levels, and apoptosis while promoting NOS3, ET-1, and NO release in HUVECs. In DVT rats, anserine reduced P-selectin, E-selectin, vWF, thrombosis, cell infiltration, apoptosis, and promoted NO release. Transcriptome sequencing and gene intervention confirmed anserine's regulation of the PI3K-Akt pathway and coagulation via MYB. CARNMT1, a regulatory enzyme for anserine metabolism, increased anserine content, inhibiting coagulation, thrombosis, cell infiltration, and promoting NO release in rats.CONCLUSION: This study confirmed anserine could alleviate DVT by improving the inflammatory response, inhibiting blood agglutination, and promoting vasodilation, providing new potential therapeutic targets, important scientific evidence for the development of DVT management, and new clues for an in-depth understanding of its molecular mechanisms.PMID:38846090 | PMC:PMC11154784 | DOI:10.3389/fphar.2024.1402758

Front Mol Neurosci. 2024 May 23;17:1375973. doi: 10.3389/fnmol.2024.1375973. eCollection 2024.ABSTRACTPost-stroke cognitive impairment (PSCI) is a major stroke consequence that has a severe impact on patients' quality of life and survival rate. For this reason, it is especially crucial to identify and intervene early in high-risk groups during the acute phase of stroke. Currently, there are no reliable and efficient techniques for the early diagnosis, appropriate evaluation, or prognostication of PSCI. Instead, plenty of biomarkers in stroke patients have progressively been linked to cognitive impairment in recent years. High-throughput omics techniques that generate large amounts of data and process it to a high quality have been used to screen and identify biomarkers of PSCI in order to investigate the molecular mechanisms of the disease. These techniques include metabolomics, which explores dynamic changes in the organism, gut microbiomics, which studies host-microbe interactions, genomics, which elucidates deeper disease mechanisms, transcriptomics and proteomics, which describe gene expression and regulation. We looked through electronic databases like PubMed, the Cochrane Library, Embase, Web of Science, and common databases for each omics to find biomarkers that might be connected to the pathophysiology of PSCI. As all, we found 34 studies: 14 in the field of metabolomics, 5 in the field of gut microbiomics, 5 in the field of genomics, 4 in the field of transcriptomics, and 7 in the field of proteomics. We discovered that neuroinflammation, oxidative stress, and atherosclerosis may be the primary causes of PSCI development, and that metabolomics may play a role in the molecular mechanisms of PSCI. In this study, we summarized the existing issues across omics technologies and discuss the latest discoveries of PSCI biomarkers in the context of omics, with the goal of investigating the molecular causes of post-stroke cognitive impairment. We also discuss the potential therapeutic utility of omics platforms for PSCI mechanisms, diagnosis, and intervention in order to promote the area's advancement towards precision PSCI treatment.PMID:38845616 | PMC:PMC11153683 | DOI:10.3389/fnmol.2024.1375973

Chem Biol Drug Des. 2024 Jun;103(6):e14564. doi: 10.1111/cbdd.14564.ABSTRACTThe leaves of Araucaria cunninghamii are known to be nonedible and toxic. Previous studies have identified biflavones in various Araucaria species. This study aimed to investigate the in vitro cytotoxicity of the isolated compounds from Araucaria cunninghamii after metabolomics and network pharmacological analysis. Methanol extract of Araucaria cunninghamii leaves was subjected to bioassay-guided fractionation. The active fraction was analyzed using LC-HRMS, through strategic database mining, by comparing the data to the Dictionary of Natural Products to identify 12 biflavones, along with abietic acid, beta-sitosterol, and phthalate. Eight compounds were screened for network pharmacology study, where in silico ADME analysis, prediction of gene targets, compound-gene-pathway network and hierarchical network analysis, protein-protein interaction, KEGG pathway, and Gene Ontology analyses were done, that showed PI3KR1, EGFR, GSK3B, and ABCB1 as the common targets for all the compounds that may act in the gastric cancer pathway. Simultaneously, four biflavones were isolated via chromatography and identified through NMR as dimeric apigenin with varying methoxy substitutions. Cytotoxicity study against the AGS cell line for gastric cancer showed that AC1 biflavone (IC50 90.58 μM) exhibits the highest cytotoxicity and monomeric apigenin (IC50 174.5 μM) the lowest. Besides, the biflavones were docked to the previously identified targets to analyze their binding affinities, and all the ligands were found to bind with energy ≤-7 Kcal/mol.PMID:38845574 | DOI:10.1111/cbdd.14564

Plant Commun. 2024 Jun 5:100984. doi: 10.1016/j.xplc.2024.100984. Online ahead of print.ABSTRACTThe soybean root system is complex. In addition to being composed of various cell types, the soybean root system includes the primary root, the lateral roots, and the nodule, an organ in which mutualistic symbiosis with the N-fixing rhizobia occurs. A mature soybean root nodule is characterized by a central infection zone where the atmospheric nitrogen is fixed and assimilated by the symbiont, resulting from the close cooperation between the plant cell and the bacteria. To date, the transcriptome of individual cells isolated from developing soybean nodules has been established, but the transcriptomic signatures of the cells of the mature soybean nodule have not yet been characterized. Applying single nucleus RNA-seq and Molecular CartographyTM technologies, we precisely characterized the transcriptomic signature of the soybean root and mature nodule cell types and revealed the co-existence of different sub-populations of B. diazoefficiens-infected cells in the mature soybean nodule including those actively involved in nitrogen fixation, and those engaged in senescence. The mining of the single cell-resolution nodule transcriptome atlas and associated gene co-expression network confirmed the role of known nodulation-related genes and identified new genes controlling the nodulation process. For instance, we functionally characterized the role of GmFWL3, a plasma membrane microdomain-associated protein controlling rhizobia infection. Our study reveals the unique cellular complexity of the mature soybean nodule and helps redefine the concept of cell types when considering the infection zone of the soybean nodule.PMID:38845198 | DOI:10.1016/j.xplc.2024.100984

Lab Anim Res. 2024 Jun 6;40(1):23. doi: 10.1186/s42826-024-00209-3.ABSTRACTBACKGROUND: The aim of the study was to develop a technique for quantitative determination of rat urine metabolites by HPLC-MS/MS, which can be used to search for biomarkers of acute intoxication with organophosphates (OPs).RESULTS: The content of metabolites in the urine of rats exposed to a single dose of paraoxon (POX1x); interval, twice daily administration of paraoxon (POX2x); exposure to 2-(o-cresyl)-4H-1, 3, 2-benzodioxaphosphorin-2-oxide and paraoxon (CBPOX) was investigated. New data were obtained on the content in the urine of intact rats as well as rats in 3 models of OP poisoning: 3-methylhistidine, threonine, creatine, creatinine, lactic acid, acetylcarnitine, inosine, hypoxanthine, adenine, 3-hydroxymethyl-butyrate and 2-hydroxymethyl-butyrate.CONCLUSIONS: The proposed assay procedure is a simple and reliable tool for urine metabolomic studies. Within 1-3 days after OP exposure in all three models of acute intoxication, the concentration of metabolites in rat urine, with the exception of adenine, changes similarly and symmetrically, regardless of the method of poisoning modeling, in all three models of acute intoxication. Further studies are needed to determine the specificity and reliability of using urinary metabolite concentration changes as potential biomarkers of acute organophosphate intoxication.PMID:38845041 | DOI:10.1186/s42826-024-00209-3