PubMed

Nat Ecol Evol. 2024 Jun 27. doi: 10.1038/s41559-024-02444-2. Online ahead of print.ABSTRACTA long-standing but poorly tested hypothesis in plant ecology and evolution is that biotic interactions play a more important role in producing and maintaining species diversity in the tropics than in the temperate zone. A core prediction of this hypothesis is that tropical plants deploy a higher diversity of phytochemicals within and across communities because they experience more herbivore pressure than temperate plants. However, simultaneous comparisons of phytochemical diversity and herbivore pressure in plant communities from the tropical to the temperate zone are lacking. Here we provide clear support for this prediction by examining phytochemical diversity and herbivory in 60 tree communities ranging from species-rich tropical rainforests to species-poor subalpine forests. Using a community metabolomics approach, we show that phytochemical diversity is higher within and among tropical tree communities than within and among subtropical and subalpine communities, and that herbivore pressure and specialization are highest in the tropics. Furthermore, we show that the phytochemical similarity of trees has little phylogenetic signal, indicating rapid divergence between closely related species. In sum, we provide several lines of evidence from entire tree communities showing that biotic interactions probably play an increasingly important role in generating and maintaining tree diversity in the lower latitudes.PMID:38937611 | DOI:10.1038/s41559-024-02444-2

Neurocrit Care. 2024 Jun 27. doi: 10.1007/s12028-024-02038-7. Online ahead of print.ABSTRACTBACKGROUND: Hypoxic-ischemic brain injury is a common cause of mortality after cardiac arrest (CA) and cardiopulmonary resuscitation; however, the specific underlying mechanisms are unclear. This study aimed to explore postresuscitation changes based on multi-omics profiling.METHODS: A CA swine model was established, and the neurological function was assessed at 24 h after resuscitation, followed by euthanizing animals. Their fecal, blood, and hippocampus samples were collected to analyze gut microbiota, metabolomics, and transcriptomics.RESULTS: The 16S ribosomal DNA sequencing showed that the microbiota composition and diversity changed after resuscitation, in which the abundance of Akkermansia and Muribaculaceae_unclassified increased while the abundance of Bifidobacterium and Romboutsia decreased. A relationship was observed between CA-related microbes and metabolites via integrated analysis of gut microbiota and metabolomics, in which Escherichia-Shigella was positively correlated with glycine. Combined metabolomics and transcriptomics analysis showed that glycine was positively correlated with genes involved in apoptosis, interleukin-17, mitogen-activated protein kinases, nuclear factor kappa B, and Toll-like receptor signal pathways.CONCLUSIONS: Our results provided novel insight into the mechanism of hypoxic-ischemic brain injury after resuscitation, which is envisaged to help identify potential diagnostic and therapeutic markers.PMID:38937417 | DOI:10.1007/s12028-024-02038-7

World J Microbiol Biotechnol. 2024 Jun 28;40(8):257. doi: 10.1007/s11274-024-04061-4.ABSTRACTIn this study, the utilization mechanism of oligosaccharides by Bifidobacterium was investigated through the transcriptome sequencing and non-targeted metabolomics technology of Bifidobacterium animalis cultured with fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS). The results showed that FOS affected the synthesis of adenosine triphosphate binding transporters (ABC transporters) by increasing the expression levels of msmE, msmG, and gluA. Similarly, GOS improved aminoacyl-tRNA synthases by upregulating the expression of tRNA-Ala, tRNA-Pro, and tRNA-Met. Bifidobacterium animalis cultured with FOS and GOS produced different metabolites, such as histamine, tartaric acid, and norepinephrine, with the functions of inhibiting inflammation, alleviating depression and diseases related to brain and nervous system and maintaining body health. Furthermore, the transcriptome and metabolome analysis results revealed that FOS and GOS promoted the growth and metabolism of Bifidobacterium animalis by regulating the related pathways of carbohydrate, energy, and amino acid metabolism. Overall, the experimental results provided significant insights into the prebiotic effects of FOS and GOS.PMID:38937374 | DOI:10.1007/s11274-024-04061-4

Plant Cell Environ. 2024 Jun 27. doi: 10.1111/pce.15019. Online ahead of print.ABSTRACTClimate warming poses major threats to temperate forests, but the response of tree root metabolism has largely remained unclear. We examined the impact of long-term soil warming (>14 years, +4°C) on the fine root metabolome across three seasons for 2 years in an old spruce forest, using a liquid chromatography-mass spectrometry platform for primary metabolite analysis. A total of 44 primary metabolites were identified in roots (19 amino acids, 12 organic acids and 13 sugars). Warming increased the concentration of total amino acids and of total sugars by 15% and 21%, respectively, but not organic acids. We found that soil warming and sampling date, along with their interaction, directly influenced the primary metabolite profiles. Specifically, in warming plots, concentrations of arginine, glycine, lysine, threonine, tryptophan, mannose, ribose, fructose, glucose and oxaloacetic acid increased by 51.4%, 19.9%, 21.5%, 19.3%, 22.1%, 23.0%, 38.0%, 40.7%, 19.8% and 16.7%, respectively. Rather than being driven by single compounds, changes in metabolite profiles reflected a general up- or downregulation of most metabolic pathway network. This emphasises the importance of metabolomics approaches in investigating root metabolic pathways and understanding the effects of climate change on tree root metabolism.PMID:38935880 | DOI:10.1111/pce.15019

Science. 2024 Jun 28;384(6703):1482-1488. doi: 10.1126/science.adm7607. Epub 2024 Jun 27.ABSTRACTHydrostatic pressure increases with depth in the ocean, but little is known about the molecular bases of biological pressure tolerance. We describe a mode of pressure adaptation in comb jellies (ctenophores) that also constrains these animals' depth range. Structural analysis of deep-sea ctenophore lipids shows that they form a nonbilayer phase at pressures under which the phase is not typically stable. Lipidomics and all-atom simulations identified phospholipids with strong negative spontaneous curvature, including plasmalogens, as a hallmark of deep-adapted membranes that causes this phase behavior. Synthesis of plasmalogens enhanced pressure tolerance in Escherichia coli, whereas low-curvature lipids had the opposite effect. Imaging of ctenophore tissues indicated that the disintegration of deep-sea animals when decompressed could be driven by a phase transition in their phospholipid membranes.PMID:38935710 | DOI:10.1126/science.adm7607

Diabetes Care. 2024 Jun 27:dc232441. doi: 10.2337/dc23-2441. Online ahead of print.ABSTRACTOBJECTIVE: We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes.RESEARCH DESIGN AND METHODS: We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10-17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0-36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors.RESULTS: Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function.CONCLUSIONS: Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.PMID:38935559 | DOI:10.2337/dc23-2441

Anal Bioanal Chem. 2024 Jun 27. doi: 10.1007/s00216-024-05399-2. Online ahead of print.ABSTRACTChiral analysis is of high interest in many fields such as chemistry, pharmaceuticals and metabolomics. Mass spectrometry and ion mobility spectrometry are useful analytical tools, although they cannot be used as stand-alone methods. Here, we propose an efficient strategy for the enantiomer characterization of amino acids (AAs) using non-covalent copper complexes. A single ion mobility monitoring (SIM2) method was applied on a TIMS-ToF mass spectrometer to maximize the detection and mobility separation of isomers. Almost all of the 19 pairs of proteinogenic AA enantiomers could be separated with at least one combination with the chiral references L-Phe and L-Pro. Furthermore, we extended the targeted SIM2 method by stitching several mobility ranges, in order to be able to analyze complex mixtures in a single acquisition while maintaining high mobility resolution. Most of the enantiomeric pairs of AAs separated with the SIM2 method were also detected with this approach. The SIM2 stitching method thus opens the way to a more comprehensive chiral analysis with TIMS-ToF instruments.PMID:38935145 | DOI:10.1007/s00216-024-05399-2

J Exp Med. 2024 Sep 2;221(9):e20232068. doi: 10.1084/jem.20232068. Epub 2024 Jun 27.ABSTRACTNuclear factor Foxp3 determines regulatory T (Treg) cell fate and function via mechanisms that remain unclear. Here, we investigate the nature of Foxp3-mediated gene regulation in suppressing autoimmunity and antitumor immune response. Contrasting with previous models, we find that Foxp3-chromatin binding is regulated by Treg activation states, tumor microenvironment, and antigen and cytokine stimulations. Proteomics studies uncover dynamic proteins within Foxp3 proximity upon TCR or IL-2 receptor signaling in vitro, reflecting intricate interactions among Foxp3, signal transducers, and chromatin. Pharmacological inhibition and genetic knockdown experiments indicate that NFAT and AP-1 protein Batf are required for enhanced Foxp3-chromatin binding in activated Treg cells and tumor-infiltrating Treg cells to modulate target gene expression. Furthermore, mutations at the Foxp3 DNA-binding domain destabilize the Foxp3-chromatin association. These representative settings delineate context-dependent Foxp3-chromatin interaction, suggesting that Foxp3 associates with chromatin by hijacking DNA-binding proteins resulting from Treg activation or differentiation, which is stabilized by direct Foxp3-DNA binding, to dynamically regulate Treg cell function according to immunological contexts.PMID:38935023 | DOI:10.1084/jem.20232068

mSystems. 2024 Jun 27:e0092923. doi: 10.1128/msystems.00929-23. Online ahead of print.ABSTRACTAirway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our understanding of host-microbe interactions, we have developed an integrated analytical and bioinformatic mass spectrometry (MS)-based metaproteomics workflow to analyze clinical bronchoalveolar lavage (BAL) samples from people with airway disease. Proteins from BAL cellular pellets were processed and pooled together in groups categorized by disease status (CF vs. non-CF) and bacterial diversity, based on previously performed small subunit rRNA sequencing data. Proteins from each pooled sample group were digested and subjected to liquid chromatography tandem mass spectrometry (MS/MS). MS/MS spectra were matched to human and bacterial peptide sequences leveraging a bioinformatic workflow using a metagenomics-guided protein sequence database and rigorous evaluation. Label-free quantification revealed differentially abundant human peptides from proteins with known roles in CF, like neutrophil elastase and collagenase, and proteins with lesser-known roles in CF, including apolipoproteins. Differentially abundant bacterial peptides were identified from known CF pathogens (e.g., Pseudomonas), as well as other taxa with potentially novel roles in CF. We used this host-microbe peptide panel for targeted parallel-reaction monitoring validation, demonstrating for the first time an MS-based assay effective for quantifying host-microbe protein dynamics within BAL cells from individual CF patients. Our integrated bioinformatic and analytical workflow combining discovery, verification, and validation should prove useful for diverse studies to characterize microbial contributors in airway diseases. Furthermore, we describe a promising preliminary panel of differentially abundant microbe and host peptide sequences for further study as potential markers of host-microbe relationships in CF disease pathogenesis.IMPORTANCEIdentifying microbial pathogenic contributors and dysregulated human responses in airway disease, such as CF, is critical to understanding disease progression and developing more effective treatments. To this end, characterizing the proteins expressed from bacterial microbes and human host cells during disease progression can provide valuable new insights. We describe here a new method to confidently detect and monitor abundance changes of both microbe and host proteins from challenging BAL samples commonly collected from CF patients. Our method uses both state-of-the art mass spectrometry-based instrumentation to detect proteins present in these samples and customized bioinformatic software tools to analyze the data and characterize detected proteins and their association with CF. We demonstrate the use of this method to characterize microbe and host proteins from individual BAL samples, paving the way for a new approach to understand molecular contributors to CF and other diseases of the airway.PMID:38934598 | DOI:10.1128/msystems.00929-23

mSystems. 2024 Jun 27:e0053224. doi: 10.1128/msystems.00532-24. Online ahead of print.ABSTRACTPrevotella copri is the dominant species of the Prevotella genus in the gut, which is genomically heterogeneous and difficult to isolate; hence, scarce research was carried out for this species. This study aimed to investigate the effect of P. copri on hyperglycemia. Thirty-nine strains were isolated from healthy individuals, and three strains (HF2123, HF1478, and HF2130) that had the highest glucose consumption were selected to evaluate the effects of P. copri supplementation on hyperglycemia. Microbiomics and non-target metabolomics were used to uncover the underlying mechanisms. Oral administration of P. copri in diabetic db/db mice increased the expression and secretion of glucagon-like peptide-1 (GLP-1), significantly improved hyperglycemia, insulin resistance, and lipid accumulation, and alleviated the pathological morphology in the pancreas, liver, and colon. P. copri changed the composition of the gut microbiota of diabetic db/db mice, which was characterized by increasing the ratio of Bacteroidetes to Firmicutes and increasing the relative abundance of genera Bacteroides, Akkermansia, and Faecalibacterium. After intervention with P. copri, fecal metabolic profiling showed that fumaric acid and homocysteine contents decreased, and glutamine contents increased. Furthermore, amino acid metabolism and cAMP/PKA signaling pathways were enriched. Our findings indicate that P. copri improved glucose metabolism abnormalities in diabetic db/db mice. Especially, one of the P. copri strains, HF2130, has shown superior performance in improving hyperglycemia, which may have the potential as a probiotic against hyperglycemia.IMPORTANCE: As a core member of the human intestinal ecosystem, Prevotelal copri has been associated with glucose metabolic homeostasis in previous studies. However, these results have often been derived from metagenomic studies, and the experimental studies have been based solely on the type of strain DSM 18205T. Therefore, more experimental evidence from additional isolates is needed to validate the results according to their high genomic heterogeneity. In this study, we isolated different branches of strains and demonstrated that P. copri could improve the metabolic profile of hyperglycemic mice by modulating microbial activity. This finding supports the causal contribution of P. copri in host glucose metabolism.PMID:38934548 | DOI:10.1128/msystems.00532-24

Ann Neurol. 2024 Jun 27. doi: 10.1002/ana.27019. Online ahead of print.ABSTRACTOBJECTIVE: Although metabolic abnormalities are implicated in the etiology of neurodegenerative diseases, their role in the development of amyotrophic lateral sclerosis (ALS) remains a subject of controversy. We aimed to identify the association between metabolic syndrome (MetS) and the risk of ALS.METHODS: This study included 395,987 participants from the UK Biobank to investigate the relationship between MetS and ALS. Cox regression model was used to estimate hazard ratios (HR). Stratified analyses were performed based on gender, body mass index (BMI), smoking status, and education level. Mediation analysis was conducted to explore potential mechanisms.RESULTS: In this study, a total of 539 cases of ALS were recorded after a median follow-up of 13.7 years. Patients with MetS (defined harmonized) had a higher risk of developing ALS after adjusting for confounding factors (HR: 1.50, 95% CI: 1.19-1.89). Specifically, hypertension and high triglycerides were linked to a higher risk of ALS (HR: 1.53, 95% CI: 1.19-1.95; HR: 1.31, 95% CI: 1.06-1.61, respectively). Moreover, the quantity of metabolic abnormalities showed significant results. Stratified analysis revealed that these associations are particularly significant in individuals with a BMI <25. These findings remained stable after sensitivity analysis. Notably, mediation analysis identified potential metabolites and metabolomic mediators, including alkaline phosphatase, cystatin C, γ-glutamyl transferase, saturated fatty acids to total fatty acids percentage, and omega-6 fatty acids to omega-3 fatty acids ratio.INTERPRETATION: MetS exhibits a robust association with an increased susceptibility to ALS, particularly in individuals with a lower BMI. Furthermore, metabolites and metabolomics, as potential mediators, provide invaluable insights into the intricate biological mechanisms. ANN NEUROL 2024.PMID:38934512 | DOI:10.1002/ana.27019

Antioxidants (Basel). 2024 May 27;13(6):653. doi: 10.3390/antiox13060653.ABSTRACTHeat stress-induced biochemical alterations in ovarian follicles compromise the function of granulosa cells (GCs) and the developmental competence of oocytes. Summer heat stress can have a far-reaching negative impact on overall fertility and reproductive success. Together with the heat stress, the rise of assisted reproductive technologies (ART), potential confounding hazards of in vitro handling and the absence of systemic body support in ART makes it imperative to study the heat stress ameliorative effects of vitamin C under in vitro conditions. Using in vitro heat stress treatment of 43 °C for two hours in bovine GCs, we studied the effects of vitamin C on cell growth, oxidative stress, apoptosis and cell cycle progression together with a comprehensive metabolomics profiling. This study investigates the molecular milieu underlying the vitamin C (VC)-led alleviation of heat-related disruptions to metabolic processes in bovine GCs. The supplementation of VC ameliorated the detrimental effects of heat stress by reducing oxidative stress and apoptosis while restoring cell proliferation. Normal cell function restoration in treated GCs was demonstrated through the finding of significantly high levels of progesterone. We observed a shift in the metabolome from biosynthesis to catabolism, mostly dominated by the metabolism of amino acids (decreased tryptophan, methionine and tyrosine) and the active TCA cycle through increased Succinic acid. The Glutathione and tryptophan metabolism were important in ameliorating the inflammation and metabolism nexus under heat stress. Two significant enzymes were identified, namely tryptophan 2,3-dioxygenase (TDO2) and mitochondrial phenylalanyl-tRNA synthetase (FARS2). Furthermore, our findings provide insight into the significance of B-complex vitamins in the context of heat stress during VC supplementation. This study underscores the importance of VC supplementation in heat stress and designates multiple metabolic intervention faucets in the context of ameliorating heat stress and enhancing reproductive efficiency.PMID:38929092 | DOI:10.3390/antiox13060653

J Hypertens. 2024 Aug 1;42(8):1307-1308. doi: 10.1097/HJH.0000000000003765. Epub 2024 Jun 27.NO ABSTRACTPMID:38934187 | DOI:10.1097/HJH.0000000000003765

Cancer Res Commun. 2024 Jun 26. doi: 10.1158/2767-9764.CRC-23-0355. Online ahead of print.ABSTRACTEscherichia coli that harbor the polyketide synthase (pks) genomic island produce colibactin and are associated with sporadic colorectal cancer development (CRC). Given the considerable prevalence of pks+ bacteria in healthy individuals, we sought to identify strategies to limit the growth and expansion of pks+ E. coli. We found that culture supernatants of the probiotic strain E. coli Nissle 1917 were able to inhibit the growth of the murine pathogenic strain pks+ E. coli NC101 (EcNC101). We performed a non-targeted analysis of the metabolome in supernatants from several E. coli strains and identified putrescine as a potential postbiotic capable of suppressing EcNC101 growth in vitro. The effect of putrescine supplementation was then evaluated in the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of CRC in mice colonized with EcNC101. Putrescine supplementation inhibited the growth of pks+ E. coli; reduced the number and size of colonic tumors; and downmodulated the release of inflammatory cytokines in the colonic lumen. Additionally, putrescine supplementation led to shifts in the composition and function of gut microbiota, characterized by an increase of the Firmicutes/Bacteroidetes ratio and enhanced acetate production. The effect of putrescine was further confirmed in vitro using a pks+ E. coli strain isolated from a CRC patient. These results suggest that probiotic-derived metabolites can be used as an alternative to live bacteria in individuals at risk of developing CRC due to the presence of pks+ bacteria in their colon.PMID:38934090 | DOI:10.1158/2767-9764.CRC-23-0355

Haematologica. 2024 Jun 27. doi: 10.3324/haematol.2023.284716. Online ahead of print.ABSTRACTThe treatment of blast phase chronic myeloid leukemia (bpCML) remains a challenge due at least in part to drug resistance of leukemia stem cells (LSCs). Recent clinical evidence suggests that the BCL-2 inhibitor venetoclax in combination with ABL-targeting tyrosine kinase inhibitors (TKIs) can eradicate bpCML LSCs. In this report, we employed preclinical models of bpCML to investigate the efficacy and underlying mechanism of LSC-targeting with venetoclax/TKI combinations. Transcriptional analysis of LSCs exposed to venetoclax and dasatinib revealed upregulation of genes involved in lysosomal biology, in particular lysosomal acid lipase A (LIPA), a regulator of free fatty acids. Metabolomic analysis confirmed increased levels of free fatty acids in response to venetoclax/dasatinib. Pre-treatment of leukemia cells with bafilomycin, a specific lysosome inhibitor, or genetic perturbation of LIPA, resulted in increased sensitivity of leukemia cells toward venetoclax/dasatinib, implicating LIPA in treatment resistance. Importantly, venetoclax/dasatinib treatment does not affect normal stem cell function, suggestive of a leukemia-specific response. These results demonstrate that venetoclax/dasatinib is an LSCselective regimen in bpCML and that disrupting LIPA and fatty acid transport enhances venetoclax/dasatinib response in targeting LSCs, providing a rationale for exploring lysosomal disruption as an adjunct therapeutic strategy to prolong disease remission.PMID:38934082 | DOI:10.3324/haematol.2023.284716

Heliyon. 2024 Jun 3;10(11):e32335. doi: 10.1016/j.heliyon.2024.e32335. eCollection 2024 Jun 15.ABSTRACTA comprehensive study of fruits and leaves extracts of Citrus medica var. sarcodactylis Swingle and Limonia acidissima L. family Rutaceae was accomplished to investigate their antiviral activity along with their zinc oxide nanoparticles formulation (ZnONPs) against the avian influenza H5N1 virus. A thorough comparative phytochemical investigation of C. medica and L.acidissima leaves and fruits was performed using UPLC-QTOF-MS-MS. Antiviral effects further aided by molecular docking proved the highly significant potential of using C. medica and L.acidissima extracts as medicinal agents. Antiviral potency is ascendingly arranged as L. acidissima leaves (LAL) > L. acidissima fruits (LAF) > C. medica leaves (CML) at 160 μg. Nano formulation of LAF has the most splendid antiviral upshot. The metabolomic profiling of CMF and LAL revealed the detection of 48 & 74 chromatographic peaks respectively. Docking simulation against five essential proteins in survival and replication of the influenza virus revealed that flavonoid di-glycosides (hesperidin, kaempferol-3-O-rutinoside, and kaempferol-7-neohesperidoside) have shown great affinity toward the five investigated proteins and achieved docking scores which approached or even exceeded that achieved by the native ligands. Hesperidin has demonstrated the best binding affinity toward neuraminidase (NA), haemagglutinin (HA), and polymerase protein PB2 (-10.675, -8.131, and -10.046 kcal/mol respectively. We propose using prepared crude methanol extracts of both plants as an antiviral agent.PMID:38933965 | PMC:PMC11200356 | DOI:10.1016/j.heliyon.2024.e32335

Front Endocrinol (Lausanne). 2024 Jun 12;15:1364609. doi: 10.3389/fendo.2024.1364609. eCollection 2024.ABSTRACTINTRODUCTION: Proliferative diabetic retinopathy (PDR) is a common diabetes complication, significantly impacting vision and quality of life. Previous studies have suggested a potential link between arginine pathway metabolites and diabetic retinopathy (DR). Connective tissue growth factor (CTGF) plays a role in the occurrence and development of fibrovascular proliferation (FVP) in PDR patients. However, the relationship between arginine pathway metabolites and FVP in PDR remains undefined. This study aimed to explore the correlation between four arginine pathway metabolites (arginine, asymmetric dimethylarginine[ADMA], ornithine, and citrulline) and the severity of FVP in PDR patients.METHODS: In this study, plasma and aqueous humor samples were respectively collected from 30 patients with age-related cataracts without diabetes mellitus (DM) and from 85 PDR patients. The PDR patients were categorized as mild-to-moderate or severe based on the severity of fundal FVP. The study used Kruskal-Wallis test to compare arginine, ADMA, ornithine, and citrulline levels across three groups. Binary logistic regression identified risk factors for severe PDR. Spearman correlation analysis assessed associations between plasma and aqueous humor metabolite levels, and between ADMA and CTGF levels in aqueous humor among PDR patients.RESULTS: ADMA levels in the aqueous humor were significantly greater in patients with severe PDR than in those with mild-to-moderate PDR(P=0.0004). However, the plasma and aqueous humor levels of arginine, ornithine, and citrulline did not significantly differ between mild-to-moderate PDR patients and severe PDR patients (P>0.05). Binary logistic regression analysis indicated that the plasma (P=0.01) and aqueous humor (P=0.006) ADMA levels in PDR patients were risk factors for severe PDR. Furthermore, significant correlations were found between plasma and aqueous humor ADMA levels (r=0.263, P=0.015) and between aqueous humor ADMA and CTGF levels (r=0.837, P<0.001).CONCLUSION: Elevated ADMA levels in plasma and aqueous humor positively correlate with the severity of FVP in PDR, indicating ADMA as a risk factor for severe PDR.PMID:38933824 | PMC:PMC11200173 | DOI:10.3389/fendo.2024.1364609

Front Vet Sci. 2024 Jun 12;11:1401592. doi: 10.3389/fvets.2024.1401592. eCollection 2024.ABSTRACTFeline chronic enteropathies (FCE) are common causes of chronic gastrointestinal signs in cats and include different diseases such as food-responsive enteropathy (FRE), inflammatory bowel diseases (IBD), and low-grade intestinal T-cell lymphoma (LGITL). Although changes in intestinal microbiota and fecal metabolites have been reported in dogs and humans with chronic enteropathy, research in cats has been limited. Therefore, this study aimed to evaluate the fecal microbiota and lipid-related fecal metabolites in cats with FCE to a clinically healthy comparison group (CG). A total of 34 cats with FCE (13 FRE, 15 IBD, and 6 LGITL) and 27 cats in the CG were enrolled in this study. The fecal microbiota was evaluated by the qPCR-based feline Dysbiosis Index (DI). The feline DI in cats with CE (median: 1.3, range: -2.4 to 3.8) was significantly higher (p < 0.0001) compared to CG (median: - 2.3, Range: -4.3 to 2.3), with no difference found among the FCE subgroups. The fecal abundances of Faecalibacterium (p < 0.0001), Bacteroides (p < 0.0001), Fusobacterium (p = 0.0398), Bifidobacterium (p = 0.0004), and total bacteria (p = 0.0337) significantly decreased in cats with FCE. Twenty-seven targeted metabolites were measured by gas chromatography-mass spectrometry, including long-chain fatty acids (LCFAs), sterols, and bile acids (BAs). Fecal concentrations of 5 of 12 LCFAs were significantly increased in cats with FCE compared to CG. Fecal concentrations of zoosterol (p = 0.0109), such as cholesterol (p < 0.001) were also significantly increased in cats with FCE, but those of phytosterols were significantly decreased in this group. No differences in fecal BAs were found between the groups. Although no differences were found between the four groups, the fecal metabolomic pattern of cats with FRE was more similar to that of the CG than to those with IBD or LGITL. This could be explained by the mild changes associated with FRE compared to IBD and LGITL. The study showed changes in intestinal microbiota and alteration of fecal metabolites in FCE cats compared to the CG. Changes in fecal lipids metabolites suggest a dysmetabolism of lipids, including LCFAs, sterols, and unconjugated BAs in cats with CE.PMID:38933703 | PMC:PMC11199873 | DOI:10.3389/fvets.2024.1401592

Front Pharmacol. 2024 Jun 11;15:1412231. doi: 10.3389/fphar.2024.1412231. eCollection 2024.ABSTRACTIntroduction: Bacillus licheniformis (B.licheniformis) was widely used in poultry feeds. However, it is still unclear about how B.licheniformis regulates the growth and development of Pekin ducks. Methods: The experiment was designed to clarify the effect and molecular mechanism of B. licheniformis on the lipid metabolism and developmental growth of Pekin ducks through multiomics analysis, including transcriptomic and metabolomic analyses. Results: The results showed that compared with the control group, the addition of 400 mg/kg B. licheniformis could significantly increase the body weight of Pekin ducks and the content of triglyceride (p < 0.05), at the same time, the addition of B. licheniformis could affect the lipid metabolism of liver in Pekin ducks, and the addition of 400 mg/kg B. licheniformis could significantly increase the content of lipoprotein lipase in liver of Pekin ducks. Transcriptomic analysis revealed that the addition of B. licheniformis primarily impacted fatty acid and glutathione, amino acid metabolism, fatty acid degradation, as well as biosynthesis and elongation of unsaturated fatty acids. Metabolomic analysis indicated that B. licheniformis primarily affected the regulation of glycerol phospholipids, fatty acids, and glycerol metabolites. Multiomics analysis demonstrated that the addition of B. licheniformis to the diet of Pekin ducks enhanced the regulation of enzymes involved in fat synthesis via the PPAR signaling pathway, actively participating in fat synthesis and fatty acid transport. Discussion: We found that B. licheniformis effectively influences fat content and lipid metabolism by modulating lipid metabolism-associated enzymes in the liver. Ultimately, this study contributes to our understanding of how B. licheniformis can improve the growth performance of Pekin ducks, particularly in terms of fat deposition, thereby providing a theoretical foundation for its practical application. Conclusion: B. licheniformis can increase the regulation of enzymes related to fat synthesis through PPAR signal pathway, and actively participate in liver fat synthesis and fatty acid transport, thus changing the lipid metabolism of Pekin ducks, mainly in the regulation of glycerol phospholipids, fatty acids and glycerol lipid metabolites.PMID:38933681 | PMC:PMC11201536 | DOI:10.3389/fphar.2024.1412231

IBRO Neurosci Rep. 2024 May 24;17:38-51. doi: 10.1016/j.ibneur.2024.05.006. eCollection 2024 Dec.ABSTRACTFirst-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve sufficient analgesia with these drugs. Opioids are considered third-line analgesics in NP due to potential severe and unpredictable adverse effects in long-term use. Also, opioid tolerance and NP may have shared mechanisms, raising further concerns about opioid use in NP. We set out to further elucidate possible shared and separate mechanisms after chronic morphine treatment and oxaliplatin-induced and diabetic polyneuropathies, and to identify potential diagnostic markers and therapeutic targets. We analysed thermal nociceptive behaviour, the transcriptome of dorsal root ganglia (DRG) and the metabolome of cerebrospinal fluid (CSF) in these three conditions, in rats. Several genes were differentially expressed, most following oxaliplatin and least after chronic morphine treatment, compared with saline-treated rats. A few genes were differentially expressed in the DRGs in all three models (e.g. Csf3r and Fkbp5). Some, e.g. Alox15 and Slc12a5, were differentially expressed in both diabetic and oxaliplatin models. Other differentially expressed genes were associated with nociception, inflammation, and glial cells. The CSF metabolome was most significantly affected in the diabetic rats. Interestingly, we saw changes in nicotinamide metabolism, which has been associated with opioid addiction and withdrawal, in the CSF of morphine-tolerant rats. Our results offer new hypotheses for the pathophysiology and treatment of NP and opioid tolerance. In particular, the role of nicotinamide metabolism in opioid addiction deserves further study.PMID:38933596 | PMC:PMC11201153 | DOI:10.1016/j.ibneur.2024.05.006