PubMed

Clin Transl Sci. 2024 Mar;17(3):e13770. doi: 10.1111/cts.13770.ABSTRACTRenal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-β (TGF-β) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-β pathway.PMID:38501942 | DOI:10.1111/cts.13770

Diabetes Metab Res Rev. 2024 Mar;40(3):e3789. doi: 10.1002/dmrr.3789.ABSTRACTAIMS: Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD.MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis.RESULTS: The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (p < 0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered.CONCLUSIONS: We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.PMID:38501707 | DOI:10.1002/dmrr.3789

New Phytol. 2024 Mar 19. doi: 10.1111/nph.19687. Online ahead of print.ABSTRACTThe plant cuticle is a hydrophobic barrier, which seals the epidermal surface of most aboveground organs. While the cuticle biosynthesis of angiosperms has been intensively studied, knowledge about its existence and composition in nonvascular plants is scarce. Here, we identified and characterized homologs of Arabidopsis thaliana fatty acyl-CoA reductase (FAR) ECERIFERUM 4 (AtCER4) and bifunctional wax ester synthase/acyl-CoA:diacylglycerol acyltransferase 1 (AtWSD1) in the liverwort Marchantia polymorpha (MpFAR2 and MpWSD1) and the moss Physcomitrium patens (PpFAR2A, PpFAR2B, and PpWSD1). Although bryophyte harbor similar compound classes as described for angiosperm cuticles, their biosynthesis may not be fully conserved between the bryophytes M. polymorpha and P. patens or between these bryophytes and angiosperms. While PpFAR2A and PpFAR2B contribute to the production of primary alcohols in P. patens, loss of MpFAR2 function does not affect the wax profile of M. polymorpha. By contrast, MpWSD1 acts as the major wax ester-producing enzyme in M. polymorpha, whereas mutations of PpWSD1 do not affect the wax ester levels of P. patens. Our results suggest that the biosynthetic enzymes involved in primary alcohol and wax ester formation in land plants have either evolved multiple times independently or undergone pronounced radiation followed by the formation of lineage-specific toolkits.PMID:38501480 | DOI:10.1111/nph.19687

J Agric Food Chem. 2024 Mar 19. doi: 10.1021/acs.jafc.3c09362. Online ahead of print.ABSTRACTMetabolomics has become an important tool in elucidating the complex relationship between a plant genotype and phenotype. For over 20 years, nuclear magnetic resonance (NMR) spectroscopy has been known for its robustness, quantitative capabilities, simplicity, and cost-efficiency. 1H NMR is the method of choice for analyzing a broad range of relatively abundant metabolites, which can be used for both capturing the plant chemical profile at one point in time and understanding the pathways that underpin plant defense. This systematic Review explores how 1H NMR-based plant metabolomics has contributed to understanding the role of various compounds in plant responses to biotic stress, focusing on both primary and secondary metabolites. It clarifies the challenges and advantages of using 1H NMR in plant metabolomics, interprets common trends observed, and suggests guidelines for method development and establishing standard procedures.PMID:38501393 | DOI:10.1021/acs.jafc.3c09362

Breastfeed Med. 2024 Mar 19. doi: 10.1089/bfm.2023.0258. Online ahead of print.ABSTRACTObjectives: This study aimed to explore the associations of growth and body composition with gut microbiome and metabolome in preterm infants. Materials and Methods: A prospective cohort study including 73 human milk-fed very preterm infants was conducted. During hospitalization, fecal samples were collected to detect microbes and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Growth and body composition indices were measured at term equivalent age (TEA) and 6 months of corrected age (CA). Associations of the fecal microbiome and metabolome profiles with growth and body composition indices, as well as their changes, were analyzed. Results: A higher abundance of Streptococcus was associated with a lower fat-free mass (FFM) z-score at 6 months of CA (p = 0.002) and a smaller increase in FFM z-score from TEA to 6 months of CA (p = 0.018). Higher levels of 3'-sialyllactose and 6'-sialyllactose (6'-SL) in feces were correlated with a lower z-score of percentage body fat (PBF) (p = 0.018 and 0.020, respectively) and a lower z-score of fat mass (p = 0.044 and 0.043, respectively) at 6 months of CA. A higher level of 6'-SL in feces was correlated with a greater increase in FFM z-score from TEA to 6 months of CA (p = 0.021). Conclusions: This study sheds light on the role of specific microbial-host interactions in metabolic changes in preterm infants, indicating the potential role of sialylated human milk oligosaccharides in optimizing body composition.PMID:38501370 | DOI:10.1089/bfm.2023.0258

Biomed Chromatogr. 2024 Mar 19:e5858. doi: 10.1002/bmc.5858. Online ahead of print.ABSTRACTThis study analyzed the endogenous metabolites and metabolic pathways in the serum of Sprague-Dawley (SD) rats gavaged with the Eerdun Wurile basic formula (EWB) using metabolomics methods and network pharmacology to explore the possible mechanism of action of the EWB in improving postoperative cognitive dysfunction (POCD). SD rats were divided into the basic formula group, which received the EWB, and the control group, which received equal amounts of distilled water. The blood was collected from the abdominal aorta and analyzed for metabolite profiles using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Network pharmacology predicts the targets of the differential metabolites and disease targets; takes the intersection and constructs a "metabolite-disease-target" network; and performs protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 56 metabolites were selected for significant differences between the groups, mainly affecting amphetamine addiction, alcoholism, and regulation of lipolysis in adipocytes. A total of 177 potential targets for differential metabolite action in POCD were selected. The PI3K-Akt pathway, the HIF-1 pathway, and the FoxO pathway were in key positions. The studies have shown that EWB could improve POCD through multicomponents, multitargets, and multipathways, providing new possibilities and reference values for the treatment of POCD.PMID:38501365 | DOI:10.1002/bmc.5858

Heliyon. 2024 Mar 5;10(6):e27597. doi: 10.1016/j.heliyon.2024.e27597. eCollection 2024 Mar 30.ABSTRACTBACKGROUND: /aims: Atherosclerosis (AS) is the common pathological basis of a variety of cardiovascular diseases (CVD), and has become the main cause of human death worldwide, and the incidence is increasing and younger trend. Ginsenoside Rb1 (Rb1), an important monomer component of the traditional Chinese herb ginseng, known for its ability to improve blood lipid disorders and anti-inflammatory. In addition, Rb1 was proved to be an effective treatment for AS. However, the effect of Rb1 on AS remains to be elucidated. The aim of this study was to investigate the mechanisms of Rb1 in ameliorating AS induced by high-fat diet (HFD).MATERIALS AND METHODS: In this study, we developed an experimental AS model in Sprague-Dawley rats by feeding HFD with intraperitoneal injection of vitamin D3. The potential therapeutic mechanism of Rb1 in AS rats was investigated by detecting the expression of inflammatory factors, microbiome 16S rRNA gene sequencing, short-chain fatty acids (SCFAs) targeted metabolomics and untargeted metabolomics.RESULTS: Rb1 could effectively alleviate the symptoms of AS and suppress the overexpression of inflammation-related factors. Meanwhile, Rb1 altered gut microbial composition and concentration of SCFAs characterized by Bacteroidetes, Actinobacteria, Lactobacillus, Prevotella, Oscillospira enrichment and Desulfovibrio depletion, accompanied by increased production of acetic acid and propionic acid. Moreover, untargeted metabolomics showed that Rb1 considerably improved faecal metabolite profiles, particularly arachidonic acid metabolism and primary bile acid biosynthesis.CONCLUSION: Rb1 ameliorated the HFD-induced AS, and the mechanism is related to improving intestinal metabolic homeostasis and inhibiting systemic inflammation by regulating gut microbiota.PMID:38500998 | PMC:PMC10945261 | DOI:10.1016/j.heliyon.2024.e27597

iScience. 2024 Feb 29;27(4):109367. doi: 10.1016/j.isci.2024.109367. eCollection 2024 Apr 19.ABSTRACTAcetylation of histones by lysine acetyltransferases (KATs) provides a fundamental mechanism by which chromatin structure and transcriptional programs are regulated. Here, we describe a dual binding activity of the first winged helix domain of human MORF KAT (MORFWH1) that recognizes the TAZ2 domain of p300 KAT (p300TAZ2) and CpG rich DNA sequences. Structural and biochemical studies identified distinct DNA and p300TAZ2 binding sites, allowing MORFWH1 to independently engage either ligand. Genomic data show that MORF/MOZWH1 colocalizes with H3K18ac, a product of enzymatic activity of p300, on CpG rich promoters of target genes. Our findings suggest a functional cooperation of MORF and p300 KATs in transcriptional regulation.PMID:38500836 | PMC:PMC10946326 | DOI:10.1016/j.isci.2024.109367

iScience. 2024 Feb 28;27(4):109345. doi: 10.1016/j.isci.2024.109345. eCollection 2024 Apr 19.ABSTRACTAfrican swine fever virus (ASFV) infection usually causes viremia within a few days. However, the metabolic changes in pig serum after ASFV infection remain unclear. In this study, serum samples collected from ASFV-infected pigs at different times were analyzed using pseudotargeted metabolomics method. Metabolomic analysis revealed the dopaminergic synapse pathway has the highest rich factor in both ASFV5 and ASFV10 groups. By disrupting the dopamine synaptic pathway, dopamine receptor antagonists inhibited ASFV replication and L-dopa promoted ASFV replication. In addition, guanosine, one of the top20 changed metabolites in both ASFV5 and ASFV10 groups suppressed the replication of ASFV. Taken together, this study revealed the changed serum metabolite profiles of ASFV-infected pigs at various times after infection and verified the effect of the changed metabolites and metabolic pathways on ASFV replication. These findings may contribute to understanding the pathogenic mechanisms of ASFV and the development of target drugs to control ASF.PMID:38500823 | PMC:PMC10946325 | DOI:10.1016/j.isci.2024.109345

Anticancer Agents Med Chem. 2024 Mar 15. doi: 10.2174/0118715206291634240312062957. Online ahead of print.ABSTRACTINTRODUCTION: Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product.METHOD: Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction.RESULTS: Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined.CONCLUSION: Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.PMID:38500290 | DOI:10.2174/0118715206291634240312062957

BMC Nutr. 2024 Mar 18;10(1):51. doi: 10.1186/s40795-024-00833-1.ABSTRACTBACKGROUND: Many developing countries, Namibia included, have a high prevalence of malnutrition among children, especially in rural subsistence farming areas where inadequate food supply is common. Poor diets in children under 5 years may result in negative health impacts. This study determined the association of food consumption patterns and nutritional status of children under 5 years from rural households in Oshana and Oshikoto regions in Namibia.METHOD: Employing a cross-sectional descriptive design, 377 children under 5 years participated in this study using purposive sampling. Validated dietary diversity and food frequency questionnaires were used to obtain information on demographic characteristics, commonly consumed food per week, and meal frequencies for the recruited children. Anthropometric measurements were obtained to assess nutritional status of children using Emergency Nutrition Assessment (ENA) software. Descriptive and inferential statistics were computed using the IBM® SPSS® Statistics (Statistical Package for Social Sciences) version 27.RESULTS: Staple foods, mostly grains, roots and tubers, along with flesh foods, legumes and nuts were commonly consumed. Vitamin A-rich fruits and vegetables were solely consumed in Oshana region (10.7%) and not in Oshikoto. Oshana exhibited a lower dietary diversity score (4±1 SD) compared to Oshikoto (5±1 SD). The prevalence of adequate feeding practices varied, with Oshana having 38.8% meeting minimum milk feeding frequency (MMFF), 55.6% minimum dietary diversity (MDD), 69.8% minimum meal frequency (MMF), and 27% minimum acceptable diet (MAD). In Oshikoto, these figures were lower at 2%, 7%, 32%, and 0.5%, respectively. Stunting, underweight, wasting, and overweight were also documented, with slight differences between the two regions. The study did not find association between nutritional status and MMFF, MDD and MAD. However, significant associations were found between specific food types, amount of food, breastfeeding length, MMF and malnutrition indicators in both regions (p<0.05).CONCLUSION: Most study participants consumed locally available staple foods. Stunting, underweight, and wasting were prevalent among children in the two regions which were significantly associated to the amount of food consumed, MMF and/ some food types. Improving food environments and eliminating access barriers to diversified diets can mitigate high prevalence of malnutrition among rural children.PMID:38500224 | DOI:10.1186/s40795-024-00833-1

J Agric Food Chem. 2024 Mar 18. doi: 10.1021/acs.jafc.4c00271. Online ahead of print.ABSTRACTAntibiotics can be accidentally introduced into farmland by wastewater irrigation, and the environmental effects are still unclear. In this study, the effects of oxytetracycline on the residue of imidacloprid in soil and radishes were investigated. Besides, the rhizosphere microbiome and radish metabolome were analyzed. It showed that the persistence of imidacloprid in soil was unchanged, but the content of olefin-imidacloprid was increased by oxytetracycline. The residue of imidacloprid in radishes was increased by nearly 1.5 times, and the hazard index of imidacloprid was significantly raised by 1.5-4 times. Oxytetracycline remodeled the rhizosphere microbiome, including Actinobe, Elusimic, and Firmicutes, and influenced the metabolome of radishes. Especially, some amino acid metabolic pathways in radish were downregulated, which might be involved in imidacloprid degradation. It can be assumed that oxytetracycline increased the imidacloprid residue in radish through disturbing the plant-rhizosphere microbiome holobiont and, thus, increased the pesticide dietary risk.PMID:38500001 | DOI:10.1021/acs.jafc.4c00271

Intern Emerg Med. 2024 Mar 18. doi: 10.1007/s11739-024-03533-7. Online ahead of print.ABSTRACTSteatotic liver disease (SLD) is characterized by hepatic fat accumulation, potentially causing major consequences such as liver decompensation. Currently, we lack medications for the treatment of SLD. Therapeutic recommendations for patients include a hypocaloric diet, weight loss, and physical activity. In particular, the Mediterranean diet is frequently recommended. However, this diet might exacerbate intestinal problems in a subset of patients with coexisting small intestinal bacterial overgrowth (SIBO). Previous studies have reported that SIBO is more predominant in patients with fatty liver than in healthy individuals. Both our research and the findings of others have highlighted a challenge related to nutritional therapy in patients with fatty liver who also suffer from SIBO inasmuch as SIBO induces several phenomena (like bloating or abdominal pain) that can adversely affect patients' quality of life and might be exacerbated by the Mediterranean diet. This may lower their adherence to the intervention. As a solution, we suggest introducing additional diagnostics (e.g., breath test) in patients with SLD who complain of SIBO-like symptoms. The next step is to modify their diets temporarily starting with several weeks of "elimination and sanitation." This would involve restricting products rich in fermentable sugars and polyols, while simultaneously treating the bacterial overgrowth. In summary, while the hypocaloric Mediterranean diet is beneficial for patients with fatty liver, those with coexisting SIBO may experience exacerbated symptoms. It is vital to consider additional diagnostics and dietary modifications for this subset of patients to address both liver and intestinal health concurrently.PMID:38499938 | DOI:10.1007/s11739-024-03533-7

EMBO J. 2024 Mar 18. doi: 10.1038/s44318-024-00064-x. Online ahead of print.ABSTRACTRegulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten-eleven translocation (TET) family of dioxygenases, and it involves a redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish that human and mouse TREG cells express Fe-regulatory genes, including that encoding ferritin heavy chain (FTH), at relatively high levels compared to conventional T helper cells. We show that FTH expression in TREG cells is essential for immune homeostasis. Mechanistically, FTH supports TET-catalyzed demethylation of CpG-rich sequences CNS1 and 2 in the FOXP3 locus, thereby promoting FOXP3 transcription and TREG cell stability. This process, which is essential for TREG lineage stability and function, limits the severity of autoimmune neuroinflammation and infectious diseases, and favors tumor progression. These findings suggest that the regulation of intracellular iron by FTH is a stable property of TREG cells that supports immune homeostasis and limits the pathological outcomes of immune-mediated inflammation.PMID:38499786 | DOI:10.1038/s44318-024-00064-x

Plant Cell Rep. 2024 Mar 18;43(4):102. doi: 10.1007/s00299-024-03167-1.ABSTRACTThe transcriptomic, phenotypic and metabolomic analysis of transgenic plants overexpressing GhMPK31 in upland cotton revealed the regulation of H2O2 burst and the synthesis of defensive metabolites by GhMPK31. Mitogen-activated protein kinases (MAPKs) are a crucial class of protein kinases, which play an essential role in various biological processes in plants. Upland cotton (G. hirsutum) is the most widely cultivated cotton species with high economic value. To gain a better understanding of the role of the MAPK gene family, we conducted a comprehensive analysis of the MAPK gene family in cotton. In this study, a total of 55 GhMPK genes were identified from the whole genome of G. hirsutum. Through an investigation of the expression patterns under diverse stress conditions, we discovered that the majority of GhMPK family members demonstrated robust responses to abiotic stress, pathogen stress and pest stress. Furthermore, the overexpression of GhMPK31 in cotton leaves led to a hypersensitive response (HR)-like cell death phenotype and impaired the defense capability of cotton against herbivorous insects. Transcriptome and metabolomics data analysis showed that overexpression of GhMPK31 enhanced the expression of H2O2-related genes and reduced the accumulation of defensive related metabolites. The direct evidence of GhMPK31 interacting with GhRBOHB (H2O2-generating protein) were found by Y2H, BiFC, and LCI. Therefore, we propose that the increase of H2O2 content caused by overexpression of GhMPK31 resulted in HR-like cell death in cotton leaves while reducing the accumulation of defensive metabolites, ultimately leading to a decrease in the defense ability of cotton against herbivorous insects. This study provides valuable insights into the function of MAPK genes in plant resistance to herbivorous insects.PMID:38499710 | DOI:10.1007/s00299-024-03167-1

Biochim Biophys Acta Mol Basis Dis. 2024 Mar 16:167096. doi: 10.1016/j.bbadis.2024.167096. Online ahead of print.ABSTRACTUnilateral nephrectomy, a procedure reducing kidney mass, triggers a compensatory response in the remaining kidney, increasing its size and function to maintain a normal glomerular filtration rate (GFR). Recent research has highlighted the role of extracellular vesicles (EVs) in renal physiology and disease, although their involvement in unilateral nephrectomy has been underexplored. In this study, unilateral nephrectomy was performed on young mice, and urinary extracellular vesicles (uEVs) characterization and cargo were analyzed. Kidney volume increased significantly post-nephrectomy, demonstrating compensatory hypertrophy. Serum creatinine, cystatin C, and urinary electrolytes concentrations were similar in both nephrectomized and control groups. Western blot analysis revealed upregulation of sodium-glucose cotransporter 2 (SGLT2) and sodium chloride cotransporter (NCC), and downregulation of sodium‑potassium-chloride co-transporter (NKCC2) and epithelial sodium channel (ENaC) in the nephrectomized group. Metabolomic analysis of uEVs showed an enrichment of certain metabolites, including citrate and stachydrine. Interestingly, uEVs from the nephrectomized group demonstrated a protective effect, downregulating signal transducer and activator of transcription 3 (STAT3) and reducing reactive oxygen species (ROS) in renal proximal cells, compared to uEVs from the control group. This study suggests that uEVs contain bioactive components capable of inducing protective, anti-inflammatory, anti-fibrinolytic, and antioxidative effects in renal cells. These findings contribute to our understanding of uEVs' role in renal compensatory mechanisms after unilateral nephrectomy and may hold promise for future therapeutic interventions in renal diseases.PMID:38499276 | DOI:10.1016/j.bbadis.2024.167096

Exp Cell Res. 2024 Mar 16:114008. doi: 10.1016/j.yexcr.2024.114008. Online ahead of print.ABSTRACTHepatocytes are responsible for maintaining a stable blood glucose concentration during periods of nutrient scarcity. The breakdown of glycogen and de novo synthesis of glucose are crucial metabolic pathways deeply interlinked with lipid metabolism. Alterations in these pathways are often associated with metabolic diseases with serious clinical implications. Studying energy metabolism in human cells is challenging. Primary hepatocytes are still considered the golden standard for in vitro studies and have been instrumental in elucidating key aspects of energy metabolism found in vivo. As a result of several limitations posed by using primary cells, a multitude of alternative hepatocyte cellular models emerged as potential substitutes. Yet, there remains a lack of clarity regarding the precise applications for which these models accurately reflect the metabolic competence of primary hepatocytes. In this study, we compared primary hepatocytes, stem cell-derived hepatocytes, adult donor-derived liver organoids, immortalized Upcyte-hepatocytes and the hepatoma cell line HepG2s in their response to a glucose production challenge. We observed the highest net glucose production in primary hepatocytes, followed by organoids, stem-cell derived hepatocytes, Upcyte-hepatocytes and HepG2s. Glucogenic gene induction was observed in all tested models, as indicated by an increase in G6PC and PCK1 expression. Lipidomic analysis revealed considerable differences across the models, with organoids showing the closest similarity to primary hepatocytes in the common lipidome, comprising 347 lipid species across 19 classes. Changes in lipid profiles as a result of the glucose production challenge showed a variety of, and in some cases opposite, trends when compared to primary hepatocytes.PMID:38499143 | DOI:10.1016/j.yexcr.2024.114008

Nat Prod Res. 2024 Mar 18:1-14. doi: 10.1080/14786419.2024.2330515. Online ahead of print.ABSTRACTClusia is one of the most important genera of the Clusiaceae family, comprising up to 400 species. This review describes the identification of twenty-two flavonoids from Clusia species, which includes five flavonols (1-4 and 11), six flavones (5-10), one catechin (12), one flavanone (13), and nine biflavonoids (14-22). O- and C-glycosylation are frequently observed amongst these flavonoids. Furthermore, seven biphenyls (23-29) and nine xanthones (30-38) have been isolated from Clusia species. Biphenyls and xanthones show limited occurrence within the genus, but together with biosynthetic insights, they might offer important chemophenetics leads for the consolidation of the genus Clusia within the Clusiaceae family. Altogether, this work provides an overview of the chemistry of the genus Clusia in terms of flavonoids, biphenyls and xanthones, as well as it discusses biological activities and chemophenetics of the isolated compounds, when appropriate.PMID:38498692 | DOI:10.1080/14786419.2024.2330515

Plants (Basel). 2024 Feb 18;13(4):552. doi: 10.3390/plants13040552.ABSTRACTMechanization is the inevitable future of tea harvesting, but its impact on tea chemistry and quality remains uncertain. Our study examines untargeted metabolomic data from 185 oolong tea products (Tieguanyin) made from leaves harvested by hand or machine based on UPLC-QToF-MS analysis. The data revealed a minimum 50% loss for over half of the chemicals in the machine-harvested group, including catechins, theaflavin, gallic acid, chlorogenic acid, and kaempferol-3-gluocside. Integrating sensory evaluation, OPLS-DA identified the six most important metabolites as significant contributors to sensory decline caused by harvesting mechanization. Furthermore, our research validates the possibility of using DD-SIMCA modelling with untargeted metabolomic data for distinguishing handpicked from machine-harvested tea products. The model was able to achieve 93% accuracy. This study provides crucial insights into the chemical and sensory shifts during mechanization, along with tools to manage and monitor these changes.PMID:38498582 | DOI:10.3390/plants13040552

PLoS One. 2024 Mar 18;19(3):e0298163. doi: 10.1371/journal.pone.0298163. eCollection 2024.ABSTRACTBACKGROUND: Traditionally Momordica charantia (Bitter gourd) is known for its blood glucose lowering potential. This has been validated by many previous studies based on rodent models but human trials are less convincing and the physiological mechanisms underlying the bioactivity of Bitter gourd are still unclear. The present study compared the effects of whole fruit or stems-leaves from five different Bitter gourd cultivars on metabolic control in adult diabetic obese Göttingen Minipigs.METHODS: Twenty streptozotocin-induced diabetic (D) obese Minipigs (body weight ~85 kg) were subdivided in mildly and overtly D pigs and fed 500 g of obesogenic diet per day for a period of three weeks, supplemented with 20 g dried powdered Bitter gourd or 20 g dried powdered grass as isoenergetic control in a cross-over, within-subject design.RESULTS: Bitter gourd fruit from the cultivars "Palee" and "Good healthy" reduced plasma fructosamine concentrations in all pigs combined (from 450±48 to 423±53 and 490±50 to 404±48 μmol/L, both p<0.03, respectively) indicating improved glycemic control by 6% and 17%. These effects were statistically confirmed in mildly D pigs but not in overtly D pigs. In mildly D pigs, the other three cultivars of fruit showed consistent numerical but no significant improvements in glycemic control. The composition of Bitter gourd fruit was studied by metabolomics profiling and analysis identified three metabolites from the class of triterpenoids (Xuedanoside H, Acutoside A, Karaviloside IX) that were increased in the cultivars "Palee" (>3.9-fold) and "Good healthy" (>8.9-fold) compared to the mean of the other three cultivars. Bitter gourd stems and leaves from the cultivar "Bilai" increased plasma insulin concentrations in all pigs combined by 28% (from 53±6 to 67±9 pmol/L, p<0.03). The other two cultivars of stems and leaves showed consistent numerical but no significant increases in plasma insulin concentrations. The effects on plasma insulin concentrations were confirmed in mildly D pigs but not in overtly D pigs.CONCLUSIONS: Fruits of Bitter gourd improve glycemic control and stems-leaves of Bitter gourd increase plasma insulin concentrations in an obese pig model for mild diabetes. The effects of Bitter gourd fruit on glycemic control seem consistent but relatively small and cultivar specific which may explain the varying results of human trials reported in the literature.PMID:38498469 | DOI:10.1371/journal.pone.0298163