PubMed

Biomolecules. 2024 Feb 28;14(3):286. doi: 10.3390/biom14030286.ABSTRACTDeath is a multifaceted process wherein each individual cell and tissue has a metabolic homeostasis and a time of functional cessation defined by the dying process as well as by intrinsic and extrinsic factors. Decomposition is physiologically associated with the release of different types of volatile organic compounds (VOCs), and these form volaboloma mortis. The main purpose of this study was to record the volabolomic fingerprint produced by volatile molecules during the physiological decomposition process of human tissue and muscle cells. The volatile chemical signature has important implications for an open issue in forensics and pathology, namely the estimation of the postmortem interval (PMI), which decreases in accuracy with the passage of time. Volatile metabolites emitted from human tissues and muscle cells at 0, 24, 48, and 72 h were recorded in real time with an electronic nose sensor device. The key findings were the continuous sampling of VOCs emitted from tissues and cells. These showed a common behavior as time progressed; particularly, after 48 h the distributions became dispersed, and after 72 h they became more variable. Volabolomic fingerprinting associated with time progression relevant to the study of PMIs was reconstructed. Additionally, there may be broader applications, such as in dog training procedures for detecting human remains, and perhaps even for studying scavenger and insect attractants.PMID:38540706 | DOI:10.3390/biom14030286

Genes (Basel). 2024 Mar 7;15(3):343. doi: 10.3390/genes15030343.ABSTRACTFenugreek (Trigonella foenum-graecum L.) is a traditional medicinal plant for treating human diseases that is widely cultivated in many countries. However, the component and related metabolic pathways are still unclear. To understand the changes in expression of the component and related genes during seed development, this study employed metabolomic and transcriptomic analyses and integrative analysis to explore the metabolites and pathways involved in the growth of fenugreek. The antifungal activity of the fenugreek seeds was also analyzed. A total of 9499 metabolites were identified in the positive ion mode, and 8043 metabolites were identified in the negative ion mode. Among them, the main components were fatty acyls, prenol lipids, steroids, steroid derivatives, flavonoids, and isoflavonoids. Among these enriched pathways, the top 20 pathways were "flavone and flavonol biosynthesis", "isoflavonoid biosynthesis", and "flavonoid biosynthesis". 3,7-Di-O-methylquercetin, flavonoids, pseudobaptigenin, isoflavonoids, methylecgonine, alkaloids, and derivatives were the most significantly upregulated metabolites. There were 38,137 differentially expressed genes (DEGs) identified via transcriptomic analysis. According to the KEGG pathway enrichment analysis, 147 DEGs were significantly enriched in "flavonoid biosynthesis". Ten DEGs of the six key enzymes were found to be involved in three pathways related to flavonoid and alkaloid synthesis in fenugreek. The antifungal activity test revealed the inhibitory effect of the ethanol extract of fenugreek seeds on Alternaria tenuissima (Kunze)Wiltshire and Magnaporthe oryzae. These findings further prove that the use of botanical pesticides in fenugreek fruit has research value.PMID:38540402 | DOI:10.3390/genes15030343

Biomedicines. 2024 Mar 14;12(3):654. doi: 10.3390/biomedicines12030654.ABSTRACTDevelopments in medicine and biology in recent decades have led to a significant increase in our knowledge of the complex interactions between the microbiota and human health. In the context of perinatal medicine and neonatology, particular attention is being paid to the potential impact of the maternal microbiota on fetal development. Among the many aspects of this relationship, the question of the impact of dysbiosis on the development of fetal heart defects is an important one. In this article, we present an analysis of recent research and scientific evidence on the relationship between a pregnant woman's microbiota and the development of fetal heart defects. We also discuss potential intervention strategies, including the role of probiotics and diet in optimising the maternal microbiota.PMID:38540267 | DOI:10.3390/biomedicines12030654

Biomedicines. 2024 Mar 7;12(3):607. doi: 10.3390/biomedicines12030607.ABSTRACTChronic kidney disease (CKD) affects approximately 12% of the global population, posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of non-dialysis-dependent (NDD) stage 5 CKD, contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in this population using semi-targeted metabolomics, which allowed us to quantify numerous metabolites with known identities before data acquisition through an in-house polar compound library. In a prospective observational design with 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high-resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5'-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (N-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in NDD stage 5 CKD, shedding light on cellular energy production and offering insights for further clinical validation.PMID:38540220 | DOI:10.3390/biomedicines12030607

Biomedicines. 2024 Feb 26;12(3):521. doi: 10.3390/biomedicines12030521.ABSTRACTTacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) has a detrimental effect on long-term kidney graft survival. However, the pathogenesis of TAC nephrotoxicity remains largely unknown. We explored it by focusing on metabolic changes in renal tissues. In this study, mice were separated into TAC and control groups (n = 5/group). TAC was administered to the TAC group (1 mg/kg/d for 28 days) subcutaneously. The control group was similarly treated with normal saline. Renal tissue metabolomes were evaluated. Renal fibrosis was observed only in the TAC group. Metabolomic analysis showed that carnitine and related metabolites were substantially lower in the TAC group than in the control group, presumably due to impaired biosynthesis and reabsorption. Low carnitine levels impair antioxidation in renal tissues and β-oxidation in mitochondria, which may lead to renal tissue damage. This metabolomic analysis revealed that carnitine deficiency in renal tissue appears to explain TAC nephrotoxicity.PMID:38540134 | DOI:10.3390/biomedicines12030521

Biomedicines. 2024 Feb 22;12(3):492. doi: 10.3390/biomedicines12030492.ABSTRACTBACKGROUND: Type 1 diabetes (T1D) is a devastating autoimmune disease, and its rising prevalence in the United States and around the world presents a critical problem in public health. While some treatment options exist for patients already diagnosed, individuals considered at risk for developing T1D and who are still in the early stages of their disease pathogenesis without symptoms have no options for any preventive intervention. This is because of the uncertainty in determining their risk level and in predicting with high confidence who will progress, or not, to clinical diagnosis. Biomarkers that assess one's risk with high certainty could address this problem and will inform decisions on early intervention, especially in children where the burden of justifying treatment is high. Single omics approaches (e.g., genomics, proteomics, metabolomics, etc.) have been applied to identify T1D biomarkers based on specific disturbances in association with the disease. However, reliable early biomarkers of T1D have remained elusive to date. To overcome this, we previously showed that parallel multi-omics provides a more comprehensive picture of the disease-associated disturbances and facilitates the identification of candidate T1D biomarkers.METHODS: This paper evaluated the use of machine learning (ML) using data augmentation and supervised ML methods for the purpose of improving the identification of salient patterns in the data and the ultimate extraction of novel biomarker candidates in integrated parallel multi-omics datasets from a limited number of samples. We also examined different stages of data integration (early, intermediate, and late) to assess at which stage supervised parametric models can learn under conditions of high dimensionality and variation in feature counts across different omics. In the late integration scheme, we employed a multi-view ensemble comprising individual parametric models trained over single omics to address the computational challenges posed by the high dimensionality and variation in feature counts across the different yet integrated multi-omics datasets.RESULTS: the multi-view ensemble improves the prediction of case vs. control and finds the most success in flagging a larger consistent set of associated features when compared with chance models, which may eventually be used downstream in identifying a novel composite biomarker signature of T1D risk.CONCLUSIONS: the current work demonstrates the utility of supervised ML in exploring integrated parallel multi-omics data in the ongoing quest for early T1D biomarkers, reinforcing the hope for identifying novel composite biomarker signatures of T1D risk via ML and ultimately informing early treatment decisions in the face of the escalating global incidence of this debilitating disease.PMID:38540105 | DOI:10.3390/biomedicines12030492

Animals (Basel). 2024 Mar 19;14(6):947. doi: 10.3390/ani14060947.ABSTRACTReactive oxygen species (ROS) are important factors that lead to a decline in sperm quality during semen preservation. Excessive ROS accumulation disrupts the balance of the antioxidant system in sperm and causes lipid oxidative damage, destroying its structure and function. Curcumin is a natural plant extract that neutralizes ROS and enhances the function of endogenous antioxidant enzymes. The effect of curcumin on the preservation of sheep semen has not been reported. This study aims to determine the effects of curcumin on refrigerated sperm (4 °C) and analyze the effects of curcumin on sperm metabolism from a Chinese native sheep (Hu sheep). The results showed that adding curcumin significantly improved (p < 0.05) the viability of refrigerated sperm at an optimal concentration of 20 µmol/L, and the plasma membrane and acrosome integrity in semen were significantly improved (p < 0.05). Adding curcumin to refrigerated semen significantly increased (p < 0.05) the levels of antioxidant enzymes (T-AOC, CAT, and SOD) and significantly decreased (p < 0.05) ROS production. A total of 13,796 metabolites in sperm and 20,581 metabolites in negative groups and curcumin-supplemented groups were identified using liquid chromatography-mass spectrometry. The proportion of lipids and lipid-like molecules among all metabolites in the sperm was the highest, regardless of treatment. We identified 50 differentially expressed metabolites (DEMs) in sperm between the negative control and curcumin-treated groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEMs were mainly enriched in the calcium signaling pathway, phospholipase D signaling pathway, sphingolipid metabolism, steroid hormone biosynthesis, 2-oxocarboxylic acid metabolism, and other metabolic pathways. The findings indicate that the addition of an appropriate concentration (20 µm/L) of curcumin to sheep semen can effectively suppress reactive oxygen species (ROS) production and extend the duration of cryopreservation (4 °C) by modulating the expression of sphingosine-1-phosphate, dehydroepiandrosterone sulfate, phytosphingosine, and other metabolites of semen. This discovery offers a novel approach to enhancing the cryogenic preservation of sheep semen.PMID:38540045 | DOI:10.3390/ani14060947

Plant Physiol Biochem. 2024 Mar 21:108549. doi: 10.1016/j.plaphy.2024.108549. Online ahead of print.ABSTRACTMedicinal plants, rich sources of valuable natural products with therapeutic potential, play a pivotal role in both traditional and modern medicine. The urgency for mass production and optimized utilization of plant secondary metabolites has intensified, particularly in response to the emergence of diseases following the COVID-19 pandemic. Groundbreaking advancements in genomics and biotechnologies have ushered in a new era of research, transforming our understanding of the biosynthesis, regulation, and manipulation of bioactive molecules in medicinal plants. This special issue serves as a convergence point for a diverse array of original research articles and reviews, collectively aiming to unveil the intricate regulatory mechanisms that govern the biosynthesis of secondary metabolites in medicinal plants. The issue delves into the exploration of the impact of both abiotic and biotic factors on the regulation of plant secondary metabolites. Furthermore, it extends its focus to innovative approaches, such as molecular breeding and synthetic biology, which provide valuable insights into modifying or enhancing the production of secondary metabolites. The special issue leverages cutting-edge techniques, including genomics, metabolomics, and microbiome characterization, to facilitate understanding the multifaceted aspects of specialized metabolism in medicinal plants. As we navigate through this scientific journey, the contributions within this special issue collectively enhance our knowledge and offer potential avenues for optimizing the production of natural products in medicinal plants.PMID:38538457 | DOI:10.1016/j.plaphy.2024.108549

J Ethnopharmacol. 2024 Mar 25:118100. doi: 10.1016/j.jep.2024.118100. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine, with the feature of synergistic effects of multi-component, multi-pathway and multi-target, plays an important role in the treatment of cancer, cardiovascular and cerebrovascular diseases, etc. However, chemical components in traditional Chinese medicine are complex and most of the pharmacological mechanisms remain unclear, especially the relationships of chemical components change during the metabolic process.AIM OF STUDY: Our aim is to provide a method based on complex network theory to analyze the causality and dynamic correlation of substances in the metabolic process of traditional Chinese medicine.MATERIALS AND METHODS: We proposed a framework named CDCS-TCM to analyze the causality and dynamic correlation between substances in the metabolic process of traditional Chinese medicine. Our method mainly consists two parts. The first part is to discover the local and global causality by the causality network. The second part is to investigate the dynamic correlations and identify the essential substance by dynamic substance correlation network.RESULTS: We developed a CDCS-TCM method to analyze the causality and dynamic correlation of substances. Using the XiangDan Injection for ischemic stroke as an example, we have identified the important substances in the metabolic process including substance pairs with strong causality and the dynamic changes of the core effector substance clusters.CONCLUSION: The proposed framework will be useful for exploring the correlations of active ingredients in traditional Chinese medicine more effectively and will provide a new perspective for the elucidation of drug action mechanisms and the new drug discovery.PMID:38537843 | DOI:10.1016/j.jep.2024.118100

Brain. 2024 Mar 27:awae097. doi: 10.1093/brain/awae097. Online ahead of print.ABSTRACTDopamine's role as the principal neurotransmitter in motor functions has long been accepted. We broaden this conventional perspective by demonstrating the involvement of non-dopaminergic mechanisms. In mouse models of Parkinson's Disease (PD), we observed that L-DOPA elicited a substantial motor response even when its conversion to dopamine was blocked by inhibiting the enzyme aromatic amino acid decarboxylase (AADC). Remarkably, the motor activity response to L-DOPA in the presence of an AADC inhibitor (NSD1015) showed a delayed onset, yet greater intensity and longer duration, peaking at 7 hours, compared to when L-DOPA was administered alone. This suggests an alternative pathway or mechanism, independent of dopamine signaling, mediating the motor functions. We sought to determine the metabolites associated with the pronounced hyperactivity observed, using comprehensive metabolomics analysis. Our results revealed that the peak in motor activity induced by NSD1015/L-DOPA in PD mice is associated with a surge (20-fold) in brain levels of the tripeptide ophthalmic acid (OA, also known as ophthalmate in its anionic form). Interestingly, we found that administering ophthalmate directly to the brain rescued motor deficits in PD mice in a dose-dependent manner. We investigated the molecular mechanisms underlying ophthalmate's action and discovered, through radioligand binding and cAMP-luminescence assays, that ophthalmate binds to and activates the calcium-sensing receptor (CaSR). Additionally, our findings demonstrated that a CaSR antagonist inhibits the motor-enhancing effects of ophthalmate, further solidifying the evidence that ophthalmate modulates motor functions through the activation of the CaSR. The discovery of ophthalmate as a novel regulator of motor function presents significant potential to transform our understanding of brain mechanisms of movement control and the therapeutic management of related disorders.PMID:38537648 | DOI:10.1093/brain/awae097

Cell Rep. 2024 Mar 21:113971. doi: 10.1016/j.celrep.2024.113971. Online ahead of print.ABSTRACTSorghum bicolor is among the most important cereals globally and a staple crop for smallholder farmers in sub-Saharan Africa. Approximately 20% of sorghum yield is lost annually in Africa due to infestation with the root parasitic weed Striga hermonthica. Existing Striga management strategies are not singularly effective and integrated approaches are needed. Here, we demonstrate the functional potential of the soil microbiome to suppress Striga infection in sorghum. We associate this suppression with microbiome-mediated induction of root endodermal suberization and aerenchyma formation and with depletion of haustorium-inducing factors, compounds required for the initial stages of Striga infection. We further identify specific bacterial taxa that trigger the observed Striga-suppressive traits. Collectively, our study describes the importance of the soil microbiome in the early stages of root infection by Striga and pinpoints mechanisms of Striga suppression. These findings open avenues to broaden the effectiveness of integrated Striga management practices.PMID:38537644 | DOI:10.1016/j.celrep.2024.113971

Cell Genom. 2024 Mar 22:100527. doi: 10.1016/j.xgen.2024.100527. Online ahead of print.ABSTRACTThe seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.PMID:38537634 | DOI:10.1016/j.xgen.2024.100527

Plant Physiol. 2024 Mar 27:kiae150. doi: 10.1093/plphys/kiae150. Online ahead of print.ABSTRACTThe hydrophobic cuticle is the first line of defense between aerial portions of plants and the external environment. On maize (Zea mays L.) silks, the cuticular cutin matrix is infused with cuticular waxes, consisting of a homologous series of very long-chain fatty acids (VLCFAs), aldehydes, and hydrocarbons. Together with VLC fatty-acyl-CoAs (VLCFA-CoAs), these metabolites serve as precursors, intermediates and end-products of the cuticular wax biosynthetic pathway. To deconvolute the potentially confounding impacts of the change in silk microenvironment and silk development on this pathway, we profiled cuticular waxes on the silks of the inbreds B73 and Mo17, and their reciprocal hybrids. Multivariate interrogation of these metabolite abundance data demonstrates that VLCFA-CoAs and total free VLCFAs are positively correlated with the cuticular wax metabolome, and this metabolome is primarily affected by changes in the silk microenvironment and plant genotype. Moreover, the genotype effect on the pathway explains the increased accumulation of cuticular hydrocarbons with a concomitant reduction in cuticular VLCFA accumulation on B73 silks, suggesting that the conversion of VLCFA-CoAs to hydrocarbons is more effective in B73 than Mo17. Statistical modeling of the ratios between cuticular hydrocarbons and cuticular VLCFAs reveals a significant role of precursor chain length in determining this ratio. This study establishes the complexity of the product-precursor relationships within the silk cuticular wax-producing network by dissecting both the impact of genotype and the allocation of VLCFA-CoA precursors to different biological processes, and demonstrates that longer chain VLCFA-CoAs are preferentially utilized for hydrocarbon biosynthesis.PMID:38537616 | DOI:10.1093/plphys/kiae150

Food Chem. 2024 Mar 23;448:139125. doi: 10.1016/j.foodchem.2024.139125. Online ahead of print.ABSTRACTIn this study, the ultrasonic-microwave pretreatment was defined as a processing technology in the production of tribute citrus powder, and it could increase the flavonoid compounds in the processing fruit powder. A total of 183 upregulated metabolites and 280 downregulated metabolites were obtained by non-targeted metabolomics, and the differential metabolites was mainly involved in the pathways of flavonoid biosynthesis, flavone and flavonol biosynthesis. A total of 8 flavonoid differential metabolites were obtained including 5 upregulated metabolites (6"-O-acetylglycitin, scutellarin, isosakuranin, rutin, and robinin), and 3 downregulated metabolites (astragalin, luteolin, and (-)-catechin gallate) by flavonoids-targeted metabolomics. The 8 flavonoid differential metabolites participated in the flavonoid biosynthesis pathways, flavone and flavonol biosynthesis pathways, and isoflavonoid biosynthesis pathways. The results provide a reference for further understanding the relationship between food processing and food components, and also lay a basis for the development of food targeted-processing technologies.PMID:38537547 | DOI:10.1016/j.foodchem.2024.139125

Reprod Biomed Online. 2023 Dec 5;48(6):103762. doi: 10.1016/j.rbmo.2023.103762. Online ahead of print.ABSTRACTMetabolomics offers new methods to identify biomarkers for oocyte and embryo quality, and for a better understanding of the physiopathology of infertility. This review investigated the latest findings regarding metabolome-derived biomarkers in follicular fluid of women with the most common types of infertility, and the potential impact on reproductive medicine outcomes. PubMed was searched for publications on metabolomics and human follicular fluid, and key biomarkers, kinetics and relationships with infertility diseases were identified. A reduced concentration of glucose and increased concentrations of lactate and pyruvate were found in follicular fluid of patients with endometriosis and diminished ovarian reserve, and the opposite was found in patients with polycystic ovary syndrome. These signatures may lead to the hypothesis of changed metabolite concentrations in patients with endometriosis and diminished ovarian reserve, and a metabolic pathway alteration with decreased aerobic glycolysis in patients with polycystic ovary syndrome. However, the pattern found in patients with endometriosis and low responders may also be expected in follicular fluid of fertile women. Larger studies are needed to confirm the results. An international database may help to highlight follicular fluid biomarkers in order to improve the selection of cryopreserved oocytes, and to enrich culture medium to restore normal metabolism and improve reproductive treatment outcomes.PMID:38537523 | DOI:10.1016/j.rbmo.2023.103762

Ecotoxicol Environ Saf. 2024 Mar 26;275:116253. doi: 10.1016/j.ecoenv.2024.116253. Online ahead of print.ABSTRACTPregnancy is a sensitive window period for bisphenol A (BPA) exposure. BPA can pass through the placenta and cause reproductive damage in offspring female mice. Even BPA that is not metabolized during lactation can be passed through milk. Cuscuta chinensis flavonoids (CCFs) can alleviate reproductive damage caused by BPA, but the mechanism of action is unclear. To investigate the potential mitigating impact of CCFs on ovarian damage resulting from BPA exposure during pregnancy, we administered BPA and CCFs to pregnant mice during the gestational period spanning from 0.5 to 17.5 days. Aseptic collection of serum and ovaries from female mice was conducted on postnatal day 21 (PND21). Serum hormone levels and tissue receptor levels were quantified utilizing ELISA and PCR, while ovaries underwent sequencing and analysis through transcriptomics and metabolomics techniques. Additionally, the assessment of ovarian oxidative stress levels was carried out as part of the comprehensive analysis. The results showed that CCFs administration mitigated the adverse effects induced by BPA exposure on ovarian index, hormone levels, receptor expression, and mRNA expression levels in female offspring mice. The joint analysis of transcriptome and metabolome revealed 48 enriched pathways in positive ion mode and 44 enriched pathways in negative ion mode. Among them, the central carbon metabolism pathway is significantly regulated by BPA and CCFs. The screened sequencing results were verified through qPCR and biochemical kits. In this study, CCFs may participate in the central carbon metabolism pathway by reducing the expression of Kit proto-oncogene (Kit), hexokinase 1 gene (Hk1) and pyruvate kinase M (Pkm) mRNA and increasing the expression of h-ras proto-oncogene (Hras), sirtuin 3 (Sirt3), sirtuin 6 (Sirt6) and TP53 induced glycolysis regulatory phosphatase gene (Tigar) mRNA, thereby resisting the effects of BPA on the body. At the same time, the metabolic levels of D-Fructose 1,6-bisphosphate and L-Asparagine tend to be stable. Moreover, CCFs demonstrated a capacity to diminish the BPA-induced escalation in reactive oxygen species (ROS) and malondialdehyde (MDA). Simultaneously, it exhibited the ability to elevate levels of glutathione (GSH) and catalase (CAT), thereby effectively preventing peroxidation. In summary, CCFs alleviate BPA-induced ovarian damage in offspring female mice by regulating the central carbon metabolism pathway. This study will improve the information on BPA reproductive damage antagonist drugs and provide a theoretical basis for protecting animal reproductive health.PMID:38537475 | DOI:10.1016/j.ecoenv.2024.116253

Phytomedicine. 2024 Jan 15;128:155366. doi: 10.1016/j.phymed.2024.155366. Online ahead of print.ABSTRACTBACKGROUND: Yinhua Miyanling tablets (YMT), comprising 10 Chinese medicinal compounds, is a proprietary Chinese medicine used in the clinical treatment of urinary tract infections. Medicinal compounds, extracts, or certain monomeric components in YMT all show good effect on ulcerative colitis (UC). However, no evidence supporting YMT as a whole prescription for UC treatment is available.PURPOSE: To evaluate the anti-UC activity of YMT and elucidate the underlying mechanisms. The objective of the study was to provide evidence for the add-on development of YMT to treat UC.METHODS: First, YMT's protective effect on the intestinal barrier was evaluated using a lipopolysaccharide (LPS)-induced Caco-2 intestinal injury model. Second, the UC mouse model was established using dextran sodium sulfate (DSS) to determine YMT's influence on symptoms, inflammatory factors, intestinal barrier, and histopathological changes in the colon. Third, an integrated method combining metabolomics and network pharmacology was employed to screen core targets and key metabolic pathways with crucial roles in YMT's therapeutic effect on UC. Molecular docking was employed to identify the key targets with high affinity. Finally, western blotting was performed to validate the mechanism of YMT action against UC.RESULTS: YMT enhanced the transepithelial electrical resistance value and improved the expression of proteins of the tight junctions dose-dependently in LPS-induced Caco-2 cells. UC mice treated with YMT exhibited alleviated pathological lesions of the colon tissue in the in vivo pharmacodynamic experiments. The colonic lengths tended to be normal, and the levels of inflammatory factors (TNF-α, IL-6, and iNOS) along with those of the core enzymes (MPO, MDA, and SOD) improved. YMT effectively ameliorated DSS-induced colonic mucosal injury; pathological changes along with ultrastructure damage were significantly alleviated (evidenced by a relatively intact colon tissue, recovery of epithelial damage, repaired gland, reduced infiltration of inflammatory cells and epithelial cells arranged closely with dense microvilli). Seven key targets (IL-6, TNF-α, MPO, COX-2, HK2, TPH, and CYP1A2) and four key metabolic pathways (arachidonic acid metabolism, linoleate metabolism, glycolysis, and gluconeogenesis and tyrosine biosynthesis) were identified to play vital roles in the treatment on UC using YMT.CONCLUSIONS: YMT exerts beneficial therapeutic effects on UC by regulating multiple endogenous metabolites, targets, and metabolic pathways, suggestive of its potential novel application in UC treatment.PMID:38537445 | DOI:10.1016/j.phymed.2024.155366

Plant Physiol Biochem. 2024 Mar 24;209:108526. doi: 10.1016/j.plaphy.2024.108526. Online ahead of print.ABSTRACTDrought stress inhibits seed germination, plant growth and development of tobacco, and seriously affects the yield and quality of tobacco leaves. However, the molecular mechanism underlying tobacco drought stress response remains largely unknown. In this study, integrated analysis of transcriptome and metabolome was performed on the germinated seeds of a cultivated variety K326 and its EMS mutagenic mutant M28 with great drought tolerance. The result showed that drought stress inhibited seed germination of the both varieties, while the germination rate of M28 was faster than that of K326 under drought stress. Besides, the levels of phytohormone ABA, GA19, and zeatin were increased by drought stress in M28. Five vital pathways were identified through integrated transcriptomic and metabolomic analysis, including zeatin biosynthesis, aspartate and glutamate synthesis, phenylamine metabolism, glutathione metabolism, and phenylpropanoid synthesis. Furthermore, 20 key metabolites in the above pathways were selected for further analysis of gene modular-trait relationship, and then four highly correlated modules were found. Then analysis of gene expression network was carried out of Top30 hub gene of these four modules, and 9 key candidate genes were identified, including HSP70s, XTH16s, APX, PHI-1, 14-3-3, SCP, PPO. In conclusion, our study uncovered some key drought-responsive pathways and genes of tobacco during seeds germination, providing new insights into the regulatory mechanisms of tobacco drought stress response.PMID:38537383 | DOI:10.1016/j.plaphy.2024.108526

Plant Physiol Biochem. 2024 Mar 19;209:108545. doi: 10.1016/j.plaphy.2024.108545. Online ahead of print.ABSTRACTWater shortage is one of the most important environmental factors limiting crop yield. In this study, we used wild soybean (Glycine soja Sieb. et Zucc.) and soybean (Glycinemax (L.) Merr.) seedlings as experimental materials, simulated drought stress using soil gravimetry, measured growth and physiological parameters, and analyzed differentially expressed genes and metabolites in the leaves of seedling by integrated transcriptomics and metabolomics techniques. The results indicate that under water deficit, Glycine soja maintained stable photosynthate by accumulating Mg2+, Fe3+, Mn2+, Zn2+ and B3+, and improved water absorption by increasing root growth. Notably, Glycine soja enhanced linoleic acid metabolism and plasma membrane intrinsic protein (PIP1) gene expression to maintain membrane fluidity, and increased pentose, glucuronate and galactose metabolism and thaumatin protein genes expression to remodel the cell wall, thereby increasing water-absorption to better tolerate to drought stress. In addition, it was found that secondary phenolic metabolism, such as phenylpropane biosynthesis, flavonoid biosynthesis and ascobate and aldarate metabolism were weakened, resulting in the collapse of the antioxidant system, which was the main reason for the sensitivity of Glycine max to drought stress. These results provide new insights into plant adaptation to water deficit and offer a theoretical basis for breeding soybean varieties with drought tolerance.PMID:38537381 | DOI:10.1016/j.plaphy.2024.108545

Cell Rep. 2024 Mar 26;43(4):114008. doi: 10.1016/j.celrep.2024.114008. Online ahead of print.ABSTRACTThe metabolic syndrome is accompanied by vascular complications. Human in vitro disease models are hence required to better understand vascular dysfunctions and guide clinical therapies. Here, we engineered an open microfluidic vessel-on-chip platform that integrates human pluripotent stem cell-derived endothelial cells (SC-ECs). The open microfluidic design enables seamless integration with state-of-the-art analytical technologies, including single-cell RNA sequencing, proteomics by mass spectrometry, and high-resolution imaging. Beyond previous systems, we report SC-EC maturation by means of barrier formation, arterial toning, and high nitric oxide synthesis levels under gravity-driven flow. Functionally, we corroborate the hallmarks of early-onset atherosclerosis with low sample volumes and cell numbers under flow conditions by determining proteome and secretome changes in SC-ECs stimulated with oxidized low-density lipoprotein and free fatty acids. More broadly, our organ-on-chip platform enables the modeling of patient-specific human endothelial tissue and has the potential to become a general tool for animal-free vascular research.PMID:38536819 | DOI:10.1016/j.celrep.2024.114008