PubMed

J Ethnopharmacol. 2024 Apr 5:118148. doi: 10.1016/j.jep.2024.118148. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herb Panax notoginseng (PN) tonifies blood, and its main active ingredient is saponin. PN is processed by different methods, resulting in different compositions and effects.AIM OF THE STUDY: To investigate changes in the microstructure and composition of fresh PN processed by different techniques and the anti-anemia effects on tumor-bearing BALB/c mice after chemotherapy with cyclophosphamide (CTX).MATERIALS AND METHODS: Fresh PN was processed by hot-air drying (raw PN, RPN), steamed at 120 °C for 5 h (steamed PN, SPN), or fried at 130 °C, 160 °C, or 200 °C for 8 min (fried PN, FPN1, FPN2, or FPN3, respectively); then, the microstructures were compared with 3D optical microscopy, quasi-targeted metabolites were detected by liquid chromatography tandem mass spectrometry (LC‒MS/MS), and saponins were detected by high-performance liquid chromatography (HPLC). An anemic mouse model was established by subcutaneous H22 cell injection and treatment with CTX. The antianemia effects of PN after processing via three methods were investigated by measuring peripheral blood parameters, performing HE staining and measuring cell proliferation via immunofluorescence.RESULTS: 3D optical profiling revealed that the surface roughness of the SPN and FPN was greater than that of the other materials. Quasi-targeted metabolomics revealed that SPN and FPN had more differentially abundant metabolites whose abundance increased, while SPN had greater amounts of terpenoids and flavones. Analysis of the composition and content of the targeted saponins revealed that the contents of rare saponins (ginsenoside Rh1, 20(S)-Rg3, 20(R)-Rg3, Rh4, Rk3, Rg5) were greater in the SPN. In animal experiments, the RBC, WBC, HGB and HCT levels in peripheral blood were increased by SPN and FPN. HE staining and immunofluorescence showed that H-SPN and M-FPN promoted bone marrow and spleen cell proliferation.CONCLUSION: The microstructure and components of fresh PN differed after processing via different methods. SPN and FPN ameliorated CTX-induced anemia in mice, but the effects of PN processed by these two methods did not differ.PMID:38583734 | DOI:10.1016/j.jep.2024.118148

Pharmacol Res. 2024 Apr 5:107169. doi: 10.1016/j.phrs.2024.107169. Online ahead of print.ABSTRACTBACKGROUND: Defining the ability of prebiotic dietary carbohydrates to influence the composition and metabolism of the gut microbiota is central to defining their health impact in diverse individuals. Many clinical trials are using indirect methods. This study aimed to validate collection and fermentation methods enabling their use in the context of clinical studies.METHODS AND RESULTS: Parameters tested included stool sample acquisition, storage, and growth conditions. Stool from 3 infants and 3 adults was collected and stored under varying conditions. Samples were cultured anaerobically for two days in the presence of prebiotics, whereupon optical density and pH were measured across time. Whole genome shotgun sequencing and NMR metabolomics were performed. Neither the type of collection vial (standard vial and two different BD anaerobic collection vials) nor cryopreservation (-80oC or 4oC) significantly influenced either microbial composition at 16hrs of anaerobic culture or the principal components of the metabolome at 8 or 16hrs. Metagenomic differences were driven primarily by subject, while metabolomic differences were driven by fermentation sugar (2'-fucosyllactose or dextrose).CONCLUSIONS: These data identified a feasible and valid approach for prebiotic fermentation analysis of individual samples in large clinical studies: collection of stool microbiota using standard vials; cryopreservation prior to testing; and collecting fermentation read-out at 8 and 16hr. Thus, fermentation analysis can be a valid technique for testing the effects of prebiotics on human fecal microbiota.PMID:38583688 | DOI:10.1016/j.phrs.2024.107169

Sci Total Environ. 2024 Apr 5:172267. doi: 10.1016/j.scitotenv.2024.172267. Online ahead of print.ABSTRACTSoils represent crucial sinks for pharmaceuticals and microplastics, making them hotspots for pharmaceuticals and plastic pollution. Despite extensive research on the toxicity of pharmaceuticals and microplastics individually, there is limited understanding of their combined effects on soil biota. This study focused on the earthworm Eisenia fetida as test organism to evaluate the biotoxicity and bioaccumulation of the typical pharmaceutical naproxen and microplastics in earthworms. Results demonstrated that high concentrations of naproxen (100 mg kg-1) significantly increased the malondialdehyde (MDA) content, inducing lipid peroxidation. Even though the low exposure of naproxen exhibits no significant influence to Eisenia fetida, the lipid peroxidation caused by higher concentration than environmental relevant concentrations necessitate attention due to temporal and spatial concentration variability found in the soil environment. Meanwhile, microplastics caused oxidative damage to antioxidant enzymes by reducing the superoxide dismutase (SOD) activity and MDA content in earthworms. Metabolome analysis revealed increased lipid metabolism in naproxen-treated group and reduced lipid metabolism in the microplastic-treated group. The co-exposure of naproxen and microplastics exhibited a similar changing trend to the microplastics-treated group, emphasizing the significant influence of microplastics. The detection of numerous including lipids like 17-Hydroxyandrostane-3-glucuronide, lubiprostone, morroniside, and phosphorylcholine, serves to identify potential biomarkers for naproxen and microplastics exposure. Additionally, microplastics increased the concentration of naproxen in earthworms at sub-organ and subcellular level. This study contributes valuable insights into the biotoxicity and distribution of naproxen and microplastics in earthworms, enhancing our understanding of their combined ecological risk to soil biota.PMID:38583628 | DOI:10.1016/j.scitotenv.2024.172267

Sci Total Environ. 2024 Apr 5:172273. doi: 10.1016/j.scitotenv.2024.172273. Online ahead of print.ABSTRACTFirefighters are frequently exposed to a variety of chemicals formed from smoke, which pose a risk for numerous diseases, including cancer. Comparative urine proteome profiling could significantly improve our understanding of the early detection of potential cancer biomarkers. In this study, for the first time, we conducted a comparative protein profile analysis of 20 urine samples collected from ten real-life firefighters prior to and following emergency fire-induced smoke. Using a label-free quantitative proteomics platform, we identified and quantified 1325 unique protein groups, of which 45 proteins showed differential expressions in abundance in response to fire-smoke exposure (post) compared to the control (pre). Pathway analysis showed proteins associated with epithelium development (e.g., RHCG, HEG1, ADAMTSL2) and Alzheimer's disease (SORL1) were significantly increased in response to smoke exposure samples. A protein-protein-network study showed a possible link between these differentially abundant proteins and the known cancer gene (TP53). Moreover, a cross-comparison analysis revealed that seven proteins-ALDH1A1, APCS, POMC, COL2A1, RDX, DDAH2, and SDC4 overlapped with the previously published urine cancer proteome datasets, suggesting a potential cancer risk. Our findings demonstrated that the discovery proteomic platform is a promising analytical technique for identifying potential non-invasive biomarkers associated with fire-smoke exposure in firefighters that may be related to cancer.PMID:38583625 | DOI:10.1016/j.scitotenv.2024.172273

Clin Chim Acta. 2024 Apr 5:117894. doi: 10.1016/j.cca.2024.117894. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Pulpitis, a pulp disease caused by caries, trauma, and other factors, has a high clinical incidence. This study focused on identifying possible metabolic biomarkers of pulpitis cases and analyzing the related metabolic pathways for providing a theoretical foundation to diagnose and prevent pulpitis.MATERIALS AND METHODS: Pulp samples from 20 pulpitis cases together with 20 normal participants were analyzed with a serum metabolomics approach using ultra-high-performance liquid chromatography (UPLC)/Orbitrap mass spectrometry. Moreover, this work carried out multivariate statistical analysis for screening potential biomarkers of pulpitis.RESULTS: Through biomarker analysis and identification, such as partial least squares discrimination analysis, orthogonal partial least squares discriminant analysis model establishment, correlation analysis, and biomarker pathway analysis, 40 biomarkers associated with 20 metabolic pathways were identified, including 20 upregulated and 20 downregulated metabolites. Those major biomarkers included oxoglutaric acid, inosine, citric acid, and PA(14:1(9Z)/PGD1). Among them, oxoglutaric acid and inosine were most significantly downregulated and had the highest correlation with pulpitis. Among these metabolic pathways, GABAergic synapse and alanine, aspartate, and glutamate metabolism were positively correlated with pulpitis. 4.CONCLUSIONS: These biomarkers as well as metabolic pathways may offer the theoretical foundation to understand pulpitis pathogenesis and develop preventive drugs.PMID:38583552 | DOI:10.1016/j.cca.2024.117894

Food Chem Toxicol. 2024 Apr 5:114632. doi: 10.1016/j.fct.2024.114632. Online ahead of print.ABSTRACTPFOA is one of the most representative compounds in the family of perfluorinated organic compounds. Due to its varying toxicity, alternatives to PFOA are beginning to emerge. HFPO-TA is an alternative for PFOA. It is currently unclear whether HFPO-TA affects glucose and lipid metabolism. In this study, rats were used as an animal model to investigate the effects of HFPO-TA on liver glucose and lipid metabolism. We found that HFPO-TA can affect glucose tolerance. Through omics analysis and molecular detection, it was found that HFPO-TA mainly affects the PPAR signaling pathway in the liver of rats, inhibiting liver glycolysis while promoting glucose production. HFPO-TA not only promotes the synthesis of fatty acids in the liver, but also promotes the breakdown of fatty acids, which ultimately leads to the disruption of hepatic glucose and lipid metabolism. The effects of HFPO-TA on metabolism are discussed in this paper to provide a reference for the risk assessment of this PFOA substitute.PMID:38583503 | DOI:10.1016/j.fct.2024.114632

Food Chem. 2024 Apr 2;449:139235. doi: 10.1016/j.foodchem.2024.139235. Online ahead of print.ABSTRACTAcidic electrolyzed oxidizing water (AEOW) was applied to suppress disease development and maintain good quality of fresh fruit. However, the involvement of AEOW in improving disease resistance of fresh longan remains unknown. Here, transcriptomic and metabolic analyses were performed to compare non-treated and AEOW-treated longan during storage. The transcriptome analysis showed AEOW-induced genes associated with phenylpropanoid and flavonoid biosynthesis. The metabolome analysis found the contents of coumarin, phenolic acid, and tannin maintained higher levels in AEOW-treated longan than non-treated longan. Moreover, the weighted correlation network analysis (WGCNA) was performed to identify hub genes, and a gene-metabolite correlation network associated with AEOW-improved disease resistance in longan was constructed by the co-analysis of transcriptomics and metabolomics. These findings identified a series of important genes and metabolites involving in AEOW-induced disease resistance of longan fruit, expanding our knowledges on fruit disease resistance and quality maintenance at the transcript and metabolic levels.PMID:38583405 | DOI:10.1016/j.foodchem.2024.139235

Biomed Pharmacother. 2024 Apr 6;174:116557. doi: 10.1016/j.biopha.2024.116557. Online ahead of print.ABSTRACTMyricanol (MY) is one of the main active components from bark of Myrica Rubra. It is demonstrated that MY rescues dexamethasone (DEX)-induced muscle dysfunction via activating silent information regulator 1 (SIRT1) and increasing adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation. Since SIRT1 and AMPK are widely involved in the metabolism of nutrients, we speculated that MY may exert beneficial effects on DEX-induced metabolic disorders. This study for the first time applied widely targeted metabolomics to investigate the beneficial effects of MY on glucose, lipids, and protein metabolism in DEX-induced metabolic abnormality in mice. The results showed that MY significantly reversed DEX-induced soleus and gastrocnemius muscle weight loss, muscle fiber damage, and muscle strength loss. MY alleviated DEX-induced metabolic disorders by increasing SIRT1 and glucose transporter type 4 (GLUT4) expressions. Additionally, myricanol prevented muscle cell apoptosis and atrophy by inhibiting caspase 3 cleavages and muscle ring-finger protein-1 (MuRF1) expression. Metabolomics showed that MY treatment reversed the serum content of carnitine ph-C1, palmitoleic acid, PS (16:0_17:0), PC (14:0_20:5), PE (P-18:1_16:1), Cer (t18:2/38:1(2OH)), four amino acids and their metabolites, and 16 glycerolipids in DEX mice. Kyoto encyclopedia of genes and genomes (KEGG) and metabolic set enrichment analysis (MSEA) analysis revealed that MY mainly affected metabolic pathways, glycerolipid metabolism, lipolysis, fat digestion and absorption, lipid and atherosclerosis, and cholesterol metabolism pathways through regulation of metabolites involved in glutathione, butanoate, vitamin B6, glycine, serine and threonine, arachidonic acid, and riboflavin metabolism. Collectively, MY can be used as an attractive therapeutic agent for DEX-induced metabolic abnormalities.PMID:38583337 | DOI:10.1016/j.biopha.2024.116557

Atherosclerosis. 2024 Mar 26;392:117527. doi: 10.1016/j.atherosclerosis.2024.117527. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Diabetic atherosclerotic vascular disease is characterized by extensive vascular calcification. However, an elevated blood glucose level alone does not explain this pathogenesis. We investigated the metabolic markers underlying diabetic atherosclerosis and whether extracellular Hsp90α (eHsp90α) triggers vascular endothelial calcification in this particular metabolic environment.METHODS: A parallel human/animal model metabolomics approach was used. We analyzed 40 serum samples collected from 24 patients with atherosclerosis and from the STZ-induced ApoE-/- mouse model. A multivariate statistical analysis of the data was performed, and mouse aortic tissue was collected for the assessment of plaque formation. In vitro, the effects of eHsp90α on endothelial cell calcification were assessed by serum analysis, Western blotting and immunoelectron microscopy.RESULTS: Diabetic ApoE-/- mice showed more severe plaque lesions and calcification damage. Stearamide, oleamide, l-thyroxine, l-homocitrulline and l-citrulline are biomarkers of diabetic ASVD; l-thyroxine was downregulated in both groups, and the thyroid sensitivity index was correlated with serum Hsp90α concentration. In vitro studies showed that eHsp90α increased Runx2 expression in endothelial cells through the LRP1 receptor. l-thyroxine reduced the increase in Runx2 levels caused by eHsp90α and affected the distribution and expression of LRP1 through hydrogen bonding with glutamine at position 1054 in the extracellular segment of LRP1.CONCLUSIONS: This study provides a mechanistic link between characteristic serum metabolites and diabetic atherosclerosis and thus offers new insight into the role of extracellular Hsp90α in promoting vascular calcification.PMID:38583286 | DOI:10.1016/j.atherosclerosis.2024.117527

EBioMedicine. 2024 Apr 6;103:105101. doi: 10.1016/j.ebiom.2024.105101. Online ahead of print.ABSTRACTBACKGROUND: Gut dysbiosis is present in chronic hepatitis B virus (HBV) infection. In this study, we integrated microbiome and metabolome analysis to investigate the role of gut microbiome in virological response to nucleos(t)ide analogues (NAs) treatment.METHODS: Chronic HBV patients were prospectively recruited for steatosis and fibrosis assessments via liver elastography, with full-length 16S sequencing performed to identify the compositional gut microbiota differences. Fasting plasma bile acids were quantified by liquid chromatography-tandem mass spectrometry.FINDINGS: All patients (n = 110) were characterized into three distinct microbial clusters by their dominant genus: c-Bacteroides, c-Blautia, and c-Prevotella. Patients with c-Bacteroides had a higher plasma ursodeoxycholic acids (UDCA) level and an increase in 7-alpha-hydroxysteroid dehydrogenase (secondary bile acid biotransformation) than other clusters. In NAs-treated patients (n = 84), c-Bacteroides was associated with higher odds of plasma HBV-DNA undetectability when compared with non-c-Bacteroides clusters (OR 3.49, 95% CI 1.43-8.96, p = 0.01). c-Blautia was positively associated with advanced fibrosis (OR 2.74, 95% CI 1.09-7.31, p = 0.04). No such associations were found in treatment-naïve patients. Increased Escherichia coli relative abundance (0.21% vs. 0.03%, p = 0.035) was found in on-treatment patients (median treatment duration 98.1 months) with advanced fibrosis despite HBV DNA undetectability. An enrichment in l-tryptophan biosynthesis was observed in patients with advanced fibrosis, which exhibited a positive correlation with Escherichia coli.INTERPRETATION: Collectively, unique bacterial signatures, including c-Bacteroides and c-Blautia, were associated with virological undetectability and fibrosis evolution during NAs therapy in chronic HBV, setting up intriguing possibilities in optimizing HBV treatment.FUNDING: This study was supported by the Guangdong Natural Science Fund (2019A1515012003).PMID:38583259 | DOI:10.1016/j.ebiom.2024.105101

Chin Med. 2024 Apr 7;19(1):58. doi: 10.1186/s13020-024-00929-7.ABSTRACTBACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated.METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation.RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota.CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.PMID:38584284 | DOI:10.1186/s13020-024-00929-7

J Anim Sci Biotechnol. 2024 Apr 8;15(1):56. doi: 10.1186/s40104-024-01014-7.ABSTRACTBACKGROUND: Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation.RESULTS: Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation.CONCLUSIONS: Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.PMID:38584279 | DOI:10.1186/s40104-024-01014-7

Signal Transduct Target Ther. 2024 Apr 8;9(1):86. doi: 10.1038/s41392-024-01791-7.ABSTRACTDuring spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.PMID:38584163 | DOI:10.1038/s41392-024-01791-7

Acta Neuropathol. 2024 Apr 7;147(1):68. doi: 10.1007/s00401-024-02713-1.ABSTRACTMutations in the pivotal metabolic isocitrate dehydrogenase (IDH) enzymes are recognized to drive the molecular footprint of diffuse gliomas, and patients with IDH mutant gliomas have overall favorable outcomes compared to patients with IDH wild-type tumors. However, survival still varies widely among patients with IDH mutated tumors. Here, we aimed to characterize molecular signatures that explain the range of IDH mutant gliomas. By integrating matched epigenome-wide methylome, transcriptome, and global metabolome data in 154 patients with gliomas, we identified a group of IDH mutant gliomas with globally altered metabolism that resembled IDH wild-type tumors. IDH-mutant gliomas with altered metabolism have significantly shorter overall survival from their IDH mutant counterparts that is not fully accounted for by recognized molecular prognostic markers of CDKN2A/B loss and glioma CpG Island Methylator Phenotype (GCIMP) status. IDH-mutant tumors with dysregulated metabolism harbored distinct epigenetic alterations that converged to drive proliferative and stem-like transcriptional profiles, providing a window to target novel dependencies in gliomas.PMID:38583102 | DOI:10.1007/s00401-024-02713-1

Biomed Environ Sci. 2024 Feb 20;37(2):133-145. doi: 10.3967/bes2024.015.ABSTRACTOBJECTIVE: Postoperative delirium (POD) has become a critical challenge with severe consequences and increased incidences as the global population ages. However, the underlying mechanism is yet unknown. Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers.METHODS: Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group. Behavioral tests were conducted 24 h before surgery and 6, 9, and 24 h after surgery. Complement C3 (C3) and S100 calcium-binding protein B protein (S100beta) levels were measured in the hippocampus, and a metabolomics analysis was performed on saliva, hippocampus, cortex, and amygdala samples.RESULTS: In total, 43, 33, 38, and 14 differential metabolites were detected in the saliva, hippocampus, cortex, and amygdala, respectively. "Pyruvate" "alpha-linolenic acid" and "2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine" are enriched in one common pathway and may be potential non-invasive biomarkers for POD. Common changes were observed in the three brain regions, with the upregulation of 1-methylhistidine and downregulation of D-glutamine.CONCLUSION: Dysfunctions in energy metabolism, oxidative stress, and neurotransmitter dysregulation are implicated in the development of POD. The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.PMID:38582976 | DOI:10.3967/bes2024.015

BMC Plant Biol. 2024 Apr 6;24(1):251. doi: 10.1186/s12870-024-04935-7.ABSTRACTBACKGROUND: Many parasitic plants of the genera Striga and Cuscuta inflict huge agricultural damage worldwide. To form and maintain a connection with a host plant, parasitic plants deploy virulence factors (VFs) that interact with host biology. They possess a secretome that represents the complement of proteins secreted from cells and like other plant parasites such as fungi, bacteria or nematodes, some secreted proteins represent VFs crucial to successful host colonisation. Understanding the genome-wide complement of putative secreted proteins from parasitic plants, and their expression during host invasion, will advance understanding of virulence mechanisms used by parasitic plants to suppress/evade host immune responses and to establish and maintain a parasite-host interaction.RESULTS: We conducted a comparative analysis of the secretomes of root (Striga spp.) and shoot (Cuscuta spp.) parasitic plants, to enable prediction of candidate VFs. Using orthogroup clustering and protein domain analyses we identified gene families/functional annotations common to both Striga and Cuscuta species that were not present in their closest non-parasitic relatives (e.g. strictosidine synthase like enzymes), or specific to either the Striga or Cuscuta secretomes. For example, Striga secretomes were strongly associated with 'PAR1' protein domains. These were rare in the Cuscuta secretomes but an abundance of 'GMC oxidoreductase' domains were found, that were not present in the Striga secretomes. We then conducted transcriptional profiling of genes encoding putatively secreted proteins for the most agriculturally damaging root parasitic weed of cereals, S. hermonthica. A significant portion of the Striga-specific secretome set was differentially expressed during parasitism, which we probed further to identify genes following a 'wave-like' expression pattern peaking in the early penetration stage of infection. We identified 39 genes encoding putative VFs with functions such as cell wall modification, immune suppression, protease, kinase, or peroxidase activities, that are excellent candidates for future functional studies.CONCLUSIONS: Our study represents a comprehensive secretome analysis among parasitic plants and revealed both similarities and differences in candidate VFs between Striga and Cuscuta species. This knowledge is crucial for the development of new management strategies and delaying the evolution of virulence in parasitic weeds.PMID:38582844 | DOI:10.1186/s12870-024-04935-7

Pediatr Res. 2024 Apr 6. doi: 10.1038/s41390-024-03140-4. Online ahead of print.ABSTRACTBACKGROUND: Growth hormone deficiency(GHD) and idiopathic short stature(ISS) are the primary causes of short stature in children. Animal experiments have revealed a link between growth hormone(GH), gut microbiota and metabolism, however, limited information is available from human trials.METHODS: Fecal samples collected from GHD (n = 36), ISS (n = 32) and healthy control (HC) children(n = 16) were subjected to microbiome (16 S rRNA gene sequencing) and metabolome (nuclear magnetic resonance,NMR) analyses.RESULTS: GHD, ISS and HC exhibit distinct differences in beta diversity of gut microbiota.In addition, short stature (GHD and ISS) exhibit higher relative abundance of Prevotellaceae_NK3B31_group at genus level compared to HC, whereas Rodentibacter, Rothia, and Pelomonas showed lower abundance. Additionally,Fusobacterium_mortiferum was identified as the characteristic species of GHD. Moreover, glucose metabolism, pyruvate metabolism and pyrimidine metabolism might play significant roles for distinguishing between GHD and normal GH groups (ISS and HC). Furthermore, a disease prediction model based on differential bacteria and metabolites between GHD and ISS exhibited high diagnostic value.CONCLUSION: These findings highlight the characteristics of different GH levels on the gut microbiota and metabolism in children, providing novel perspectives for early diagnosis and prognostic treatment of short stature with abnormal GH levels.IMPACT: The key message of our study is to identify human-relevant gut microbiota and host metabolic patterns that are interfered with growth hormone levels, and to develop biomarker models to identify short stature associated with growth hormone deficiency. We used idiopathic short stature as a control group for growth hormone deficiency, complementing the absence of height as a factor in the existing literature. Our study ultimately hopes to shed new light on the diagnosis and treatment of short stature children associated with growth hormone deficiency.PMID:38582946 | DOI:10.1038/s41390-024-03140-4

IMA Fungus. 2024 Apr 7;15(1):10. doi: 10.1186/s43008-024-00141-0.ABSTRACTThe Apiospora genus comprises filamentous fungi with promising potential, though its full capabilities remain undiscovered. In this study, we present the first genome assembly of an Apiospora arundinis isolate, demonstrating a highly complete and contiguous assembly estimated to 48.8 Mb, with an N99 of 3.0 Mb. Our analysis predicted a total of 15,725 genes, with functional annotations for 13,619 of them, revealing a fungus capable of producing very high amounts of carbohydrate-active enzymes (CAZymes) and secondary metabolites. Through transcriptomic analysis, we observed differential gene expression in response to varying growth media, with several genes related to carbohydrate metabolism showing significant upregulation when the fungus was cultivated on a hay-based medium. Finally, our metabolomic analysis unveiled a fungus capable of producing a diverse array of metabolites.PMID:38582937 | DOI:10.1186/s43008-024-00141-0

Cell Death Dis. 2024 Apr 6;15(4):249. doi: 10.1038/s41419-024-06633-6.ABSTRACTAcyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAAR) γ2 subunit (GABAARγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAARγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists. For this, we built a molecular model of the interaction of ACBP/DBI with peptides derived from GABAARγ2. We then validated the interaction between recombinant and native ACBP/DBI protein and a GABAARγ2-derived eicosapeptide (but not its F77I mutant) by pull down experiments or surface plasmon resonance. The GABAARγ2-derived eicosapeptide inhibited the metabolic activation of hepatocytes by recombinant ACBP/DBI protein in vitro. Moreover, the GABAARγ2-derived eicosapeptide (but not its F77I-mutated control) blocked appetite stimulation by recombinant ACBP/DBI in vivo, induced autophagy in the liver, and protected mice against the hepatotoxin concanavalin A. We conclude that peptidomimetics disrupting the interaction between ACBP/DBI and GABAARγ2 might be used as ACBP/DBI antagonists. This strategy might lead to the future development of clinically relevant small molecules of the ACBP/DBI system.PMID:38582872 | DOI:10.1038/s41419-024-06633-6

Br J Cancer. 2024 Apr 6. doi: 10.1038/s41416-024-02670-2. Online ahead of print.ABSTRACTBACKGROUND: Mitochondrial dynamics play a fundamental role in determining stem cell fate. However, the underlying mechanisms of mitochondrial dynamics in the stemness acquisition of cancer cells are incompletely understood.METHODS: Metabolomic profiling of cells were analyzed by MS/MS. The genomic distribution of H3K27me3 was measured by CUT&Tag. Oral squamous cell carcinoma (OSCC) cells depended on glucose or glutamine fueling TCA cycle were monitored by 13C-isotope tracing. Organoids and tumors from patients and mice were treated with DRP1 inhibitors mdivi-1, ferroptosis inducer erastin, or combination with mdivi-1 and erastin to evaluate treatment effects.RESULTS: Mitochondria of OSCC stem cells own fragment mitochondrial network and DRP1 is required for maintenance of their globular morphology. Imbalanced mitochondrial dynamics induced by DRP1 knockdown suppressed stemness of OSCC cells. Elongated mitochondria increased α-ketoglutarate levels and enhanced glutaminolysis to fuel the TCA cycle by increasing glutamine transporter ASCT2 expression. α-KG promoted the demethylation of histone H3K27me3, resulting in downregulation of SNAI2 associated with stemness and EMT. Significantly, suppressing DRP1 enhanced the anticancer effects of ferroptosis.CONCLUSION: Our study reveals a novel mechanism underlying mitochondrial dynamics mediated cancer stemness acquisition and highlights the therapeutic potential of mitochondria elongation to increase the susceptibility of cancer cells to ferroptosis.PMID:38582810 | DOI:10.1038/s41416-024-02670-2