PubMed

Expert Rev Neurother. 2024 Oct 22:1-14. doi: 10.1080/14737175.2024.2415985. Online ahead of print.ABSTRACTINTRODUCTION: Alzheimer's disease (AD) is the most common neurodegenerative disorder, which is characterized by a progressive loss of cognitive functions. The high prevalence, chronicity, and multimorbidity are very common in AD, which significantly impair the quality of life and functioning of patients. Early detection and accurate diagnosis of Alzheimer's disease (AD) can stop the illness from progressing thereby postponing its symptoms. Therefore, for the early diagnosis and monitoring of AD, more sensitive, noninvasive, straightforward, and affordable screening tools are needed.AREAS COVERED: This review summarizes the importance of early detection methods and novel techniques for Alzheimer's disease diagnosis that can be used by healthcare professionals.EXPERT OPINION: Early diagnosis assists the patient and caregivers to understand the problem establishing reasonable goals and making future plans together. Early diagnosis techniques not only help in monitoring disease progression but also provide crucial information for the development of novel therapeutic targets. Researchers can plan to potentially alleviate symptoms or slow down the progression of Alzheimer's disease by identifying early molecular changes and targeting altered pathways.PMID:39435792 | DOI:10.1080/14737175.2024.2415985

Neural Regen Res. 2024 Oct 22. doi: 10.4103/NRR.NRR-D-24-00531. Online ahead of print.ABSTRACTAge-related macular degeneration Is a serious neurodegenerativo disease of the retina that significantly impacts vision. Unfortunately, the specific pathogenesis remains unclear, and effective early treatment options are consequently lacking. The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host. The intestinal microbiome undergoes dynamic changes owing to age, diet, genetics, and other factors. Such dysregulation of the intestinal flora can disrupt the microecological balance, resulting in immunological and metabolic dysfunction in the host, and affecting the development of many diseases. In recent decades, significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract, including the brain. Indeed, several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Similarly, the role of the "gut-eye axis" has been confirmed to play a role in the pathogenesis of many ocular disorders. Moreover, age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies. As such, the intestinal flora may play an important role in age-related macular degeneration. Given the above context, the present review aims to clarify the gut-brain and gut-eye connections, assess the effect of intestinal flora and metabolites on age-related macular degeneration, and identify potential diagnostic markers and therapeutic strategies. Currently, direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited, while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration. Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions, while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.PMID:39435619 | DOI:10.4103/NRR.NRR-D-24-00531

Adv Sci (Weinh). 2024 Oct 22:e2309331. doi: 10.1002/advs.202309331. Online ahead of print.ABSTRACTCD169+ macrophages are a newly defined macrophage subpopulation that can recognize and bind with other cells through related ligands, playing an essential role in antigen presentation and immune tolerance. However, its role in Allergic Rhinitis (AR) is still unclear. To investigate the characteristics of CD169+ macrophages in AR, this work first detects their expression patterns in the nasal mucosa of clinical patients. These results show a significant increase in CD169+ macrophages in the nasal mucosa of patients with AR. Subsequently, this work establishes an animal AR model using CD169 transgenic mice and compared the advantages of the two models. Moreover, this work also demonstrates the effects of CD169 knockout on eosinophils, Th cells, Treg cells, and the migration of dendritic cells (DCs). In addition, this metabolomic data shows that CD169+ macrophages can upregulate alanine production and increase reactive oxygen species (ROS) levels. This process may be mediated through the Keap1/Nrf2/HO-1 signaling pathway. In addition, this work also finds that SLC38A2 plays an essential role in the process of CD169+ macrophages promoting alanine uptake by DCs. This study confirms that CD169+ macrophages can upregulate their internal alanine production and increase ROS levels through the Keap1/Nrf2/HO-1 axis, playing an irreplaceable role in AR.PMID:39435598 | DOI:10.1002/advs.202309331

Mol Genet Metab Rep. 2024 Oct 5;41:101145. doi: 10.1016/j.ymgmr.2024.101145. eCollection 2024 Dec.ABSTRACTAutosomal dominant congenital disorder of glycosylation (CDG) type Iw (OMIM# 619714) is caused by a heterozygous mutation in the STT3A gene. Most CDGs have an autosomal recessive (AR) mode of inheritance, but several cases with an autosomal dominant (AD) form of an AR CDG have been recently identified. This report describes a 17-year-old male who was referred to the Undiagnosed Diseases Network (UDN) with a history of macrocephaly, failure to thrive, short stature, epilepsy, autism, attention-deficit/hyperactivity disorder, mild developmental delay, intermittent hypotonia, dysmorphic features, and mildly enlarged aortic root. Trio exome sequencing was negative. His biochemical workup included normal plasma amino acids, ammonia, acylcarnitine profile and urine organic and amino acids. His UDN genome sequencing (GS) identified a previously unreported de novo STT3A variant (c.1631A > G: p.Asn544Ser). This variant removes a glycosylation site and was predicted to be destabilizing by structural biology modeling. The patient was formally diagnosed by the UDN Metabolomics Core as having an abnormal transferrin profile indicative of CDG type Iw through metabolomic profiling. We report here an affected male with phenotypic, molecular, and metabolic findings consistent with CDG type Iw due to a heterozygous STT3A variant. This case highlights the importance of further testing of individuals with the phenotypic and metabolic findings of an AR disorder who are heterozygous for a single disease-causing allele and can be shown to have a new AD form of the disorder that represents clinical heterogeneity.PMID:39435313 | PMC:PMC11491968 | DOI:10.1016/j.ymgmr.2024.101145

Front Plant Sci. 2024 Oct 7;15:1468858. doi: 10.3389/fpls.2024.1468858. eCollection 2024.ABSTRACTCoconut meat and coconut water have garnered significant attention for their richness in healthful flavonoids. However, the dynamics of flavonoid metabolites in coconut water during different developmental stages remain poorly understood. This study employed the metabolomics approach using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the changes in flavonoid metabolite profiles in coconut water from two varieties, 'Wenye No.5'(W5) and Hainan local coconut (CK), across six developmental stages. The results showed that a total of 123 flavonoid metabolites including chalcones, dihydroflavonoids, dihydroflavonols, flavonoids, flavonols, flavonoid carboglycosides, and flavanols were identified in the coconut water as compared to the control. The total flavonoid content in both types of coconut water exhibited a decreasing trend with developmental progression, but the total flavonoid content in CK was significantly higher than that in W5. The number of flavonoid metabolites that differed significantly between the W5 and CK groups at different developmental stages were 74, 74, 60, 92, 40 and 54, respectively. KEGG pathway analysis revealed 38 differential metabolites involved in key pathways for flavonoid biosynthesis and secondary metabolite biosynthesis. This study provides new insights into the dynamics of flavonoid metabolites in coconut water and highlights the potential for selecting and breeding high-quality coconuts with enhanced flavonoid content. The findings have implications for the development of coconut-based products with improved nutritional and functional properties.PMID:39435019 | PMC:PMC11491327 | DOI:10.3389/fpls.2024.1468858

RSC Adv. 2024 Oct 21;14(45):33034-33047. doi: 10.1039/d4ra05758a. eCollection 2024 Oct 17.ABSTRACTEndophytes acquire flavonoid biosynthetic genes from the host medicinal plants. Despite tea (Camellia sinensis (L.) Kuntze) being the major source of bioactive catechins, catechin-producing endophytic fungi have never been reported from the tea plant. Here, we report the isolation and characterization of catechin-producing endophytic fungi isolated from tea leaves, their chemical characterization, and associated bioactivities. Among the nine isolated endophytes, two (CSPL6 and CSPL5b) produced catechin (381.48 and 166.40 μg per mg extract) and epigallocatechin-o-gallate (EGCG; 484.41 and 281.99 μg per mg extract) as quantified by high-performance liquid chromatography (HPLC). The isolates were identified as Pseudopestalotiopsis camelliae-sinensis and Didymella sinensis based on molecular and morphological characterization. Untargeted metabolomics using gas-chromatography mass spectroscopy (GCMS) revealed the presence of several bioactive phytochemicals mostly belonging to tyrosols, pyridoxines, fatty acids, aminopyrimidine, and benzenetriol classes. Metabolic pathways pertaining to the biosynthesis of unsaturated fatty acids (UFAs), butanoate metabolism, and linoleic acid metabolism were highly enriched in both catechin-producing isolates. The isolates were able to differentially scavenge intracellular O2 and N2 free-radicals, but CSPL5b demonstrated relatively superior bioactivities compared to CSPL6. Both isolates stimulated the growth of various probiotic strains, indicating prebiotic effects that are otherwise known to be associated with catechins. Collectively, the current study demonstrated that fungal endophytes CSPL6 and CSPL5b, isolated from tea leaves, could be used as alternative sources of catechins, and hold promising potential in evidence-based therapeutics.PMID:39434990 | PMC:PMC11492194 | DOI:10.1039/d4ra05758a

J Alzheimers Dis Rep. 2024 Jul 23;8(1):1093-1104. doi: 10.3233/ADR-230154. eCollection 2024.ABSTRACTBACKGROUND: Previous studies found that visual impairment (VI) is associated with higher risk of cognitive impairment, but the molecular basis of these conditions is unknown.OBJECTIVE: We aim to compare the metabolite associations of VI and cognitive impairment.METHODS: The study population with comprehensive measurements was derived from the UK Biobank study. Visual acuity worse than 0.3 logMAR units were defined as VI. Failure in one or more of the four cognitive tests was defined as cognitive impairment. A panel of 249 metabolites was measured using a nuclear magnetic resonance metabolites profiling platform. Logistic regression models were applied to compare metabolite associations with VI and cognitive impairment.RESULTS: 23,775 participants with complete data on visual acuity, cognitive tests and metabolomics, and without a history of neurological disorders at baseline were included. After adjusting for confounding factors, VI was significantly associated with cognitive impairment (odds ratio[OR] = 1.49, 95% confidence interval [CI]: 1.27-1.74, p < 0.001). After multiple testing correction (p < 9×10-4), five metabolites including the ratio of omega-6 to omega-3 fatty acids (FAs) (OR = 1.18[1.10-1.27]), ratio of omega-3 to total FAs (OR = 0.84[0.77-0.91]), ratio of docosahexaenoic acid (DHA) to total FAs (OR = 0.86[0.80-0.94]), DHA (OR = 0.85[0.78-0.92]), and omega-3 FAs (OR = 0.84[0.77-0.91]) were uniquely associated with VI. Glycoprotein acetyls (OR = 1.06[1.03-1.10]) and alanine (OR = 0.95[0.92-0.98]) were exclusively associated with cognitive impairment. Albumin was identified as the common metabolite shared by the two phenotypes (OR = 0.90[0.85-0.95] for VI, and 0.95[0.92-0.98]) for cognitive impairment).CONCLUSIONS: We identified distinct and overlapping metabolites associated with VI and cognitive impairment, unveiling their distinct metabolic profiles and potential common pathophysiology.PMID:39434817 | PMC:PMC11491940 | DOI:10.3233/ADR-230154

Korean J Intern Med. 2024 Oct 22. doi: 10.3904/kjim.2024.111. Online ahead of print.ABSTRACTDiabetic nephropathy (DN), a leading cause of chronic kidney disease and end-stage kidney disease (ESKD), poses global health challenges given its increasing prevalence. DN increases the risk of mortality and cardiovascular events. Early identification and appropriate DN management are crucial. However, current diagnostic methods rely on general traditional markers, highlighting the need for DN-specific diagnostics. Metabolomics, the study of small molecules produced by metabolic activity, promises to identify specific biomarkers that distinguish DN from other kidney diseases, decode the underlying disease mechanisms, and predict the disease course. Profound changes in metabolic pathways are apparent in individuals with DN, alterations in the tricarboxylic acid cycle and amino acid and lipid metabolism, suggestive of mitochondrial dysfunction. Metabolomics aids prediction of chronic kidney disease progression; several metabolites serve as indicators of renal functional decline and the risk of ESKD. Integration of such information with other omics data will further enhance our understanding of DN, paving the way to personalized treatment. In summary, metabolomics and multi-omics offer valuable insights into DN and are promising diagnostic and prognostic tools.PMID:39434603 | DOI:10.3904/kjim.2024.111

Biomed Chromatogr. 2024 Oct 21:e6029. doi: 10.1002/bmc.6029. Online ahead of print.ABSTRACTGiven the genetic and clinical overlap observed between schizophrenia and depression, the present study was to identify the similarities and differences in serum metabolic profiles between patients with schizophrenia and depression. Global metabolomics research methods based on UHPLC-QTOF-MS/MS were performed. A total of 113 and 118 differential metabolites were screened and identified in depression and schizophrenia groups, respectively, as compared to health control; among those, 94 differential metabolites were shared by both. Pathway analysis indicated arginine and proline metabolism, alanine, aspartate, and glutamate metabolism were two significant metabolic pathways both in depression and schizophrenia groups as compared with health control groups, respectively. Similarly, 77 differential metabolites were identified between depression and schizophrenia groups, in which, serum N-acetylglutamine and isovalerylglycine levels showed significant differences between patients with depression and schizophrenia with p values less than 0.001 and without significant outliers. Sphingolipid metabolism was identified as a significant metabolic pathway distinguishing between depression and schizophrenia groups based on pathway analysis. Conclusively, common alterations in arginine and proline metabolism, alanine, aspartate, and glutamate metabolism were observed in patients with schizophrenia and depression; whereas differences in serum N-acetylglutamine and isovalerylglycine levels as well as sphingolipid metabolism were discovered between the two categories of patients.PMID:39434479 | DOI:10.1002/bmc.6029

Genome Med. 2024 Oct 21;16(1):120. doi: 10.1186/s13073-024-01395-4.ABSTRACTBACKGROUND: Altered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites and proteins associating with cardiac disease.METHODS: Mendelian randomisation (MR) was used to assess the association of 174 metabolites measured in up to 86,507 participants with AF, HF, dilated cardiomyopathy (DCM), and non-ischemic cardiomyopathy (NICM). Subsequently, we sourced data on 1567 plasma proteins and performed cis MR to identify proteins affecting the identified metabolites as well as the cardiac diseases. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways.RESULTS: We identified 35 metabolites associating with cardiac disease. AF was affected by seventeen metabolites, HF by nineteen, DCM by four, and NCIM by taurine. HF was particularly enriched for phosphatidylcholines (p = 0.029) and DCM for acylcarnitines (p = 0.001). Metabolite involvement with AF was more uniform, spanning for example phosphatidylcholines, amino acids, and acylcarnitines. We identified 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. We recapitulated known associations, for example between the drug target of digoxin (AT1B2), taurine and NICM risk. Additionally, we identified numerous novel findings, such as higher RET values associating with phosphatidylcholines and decreasing AF and HF. RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy homeostasis in cardiac pathogenesis.CONCLUSIONS: This study identified 35 plasma metabolites involved with cardiac diseases and linked these to 38 druggable proteins, providing actionable leads for drug development.PMID:39434187 | DOI:10.1186/s13073-024-01395-4

Microbiome. 2024 Oct 21;12(1):208. doi: 10.1186/s40168-024-01932-8.ABSTRACTBACKGROUND: The disease resistance phenotype is closely related to immunomodulatory function and immune tolerance and has far-reaching implications in animal husbandry and human health. Microbes play an important role in the initiation, prevention, and treatment of diseases, but the mechanisms of host-microbiota interactions in disease-resistant phenotypes are poorly understood. In this study, we hope to uncover and explain the role of microbes in intestinal diseases and their mechanisms of action to identify new potential treatments.METHODS: First, we established the colitis model of DSS in two breeds of sheep and then collected the samples for multi-omics testing including metagenes, metabolome, and transcriptome. Next, we made the fecal bacteria liquid from the four groups of sheep feces collected from H-CON, H-DSS, E-CON, and E-DSS to transplant the fecal bacteria into mice. H-CON feces were transplanted into mice named HH group and H-DSS feces were transplanted into mice named HD group and Roseburia bacteria treatment named HDR groups. E-CON feces were transplanted into mice named EH group and E-DSS feces were transplanted into mice in the ED group and Roseburia bacteria treatment named EDR groups. After successful modeling, samples were taken for multi-omics testing. Finally, colitis mice in HD group and ED group were administrated with Roseburia bacteria, and the treatment effect was evaluated by H&E, PAS, immunohistochemistry, and other experimental methods.RESULTS: The difference in disease resistance of sheep to DSS-induced colitis disease is mainly due to the increase in the abundance of Roseburia bacteria and the increase of bile acid secretion in the intestinal tract of Hu sheep in addition to the accumulation of potentially harmful bacteria in the intestine when the disease occurs, which makes the disease resistance of Hu sheep stronger under the same disease conditions. However, the enrichment of harmful microorganisms in East Friesian sheep activated the TNFα signalling pathway, which aggravated the intestinal injury, and then the treatment of FMT mice by culturing Roseburia bacteria found that Roseburia bacteria had a good curative effect on colitis.CONCLUSION: Our study showed that in H-DSS-treated sheep, the intestinal barrier is stabilized with an increase in the abundance of beneficial microorganisms. Our data also suggest that Roseburia bacteria have a protective effect on the intestinal barrier of Hu sheep. Accumulating evidence suggests that host-microbiota interactions are associated with IBD disease progression. Video Abstract.PMID:39434180 | DOI:10.1186/s40168-024-01932-8

BMC Genomics. 2024 Oct 21;25(1):984. doi: 10.1186/s12864-024-10903-0.ABSTRACTBACKGROUND: Hydrogen peroxide (H2O2), a novel water treatment agent, can be used for disinfection, water quality adjustment, and disease prevention, while excessive H2O2 can injure farm animals, even leading to death. Hydrogen peroxide is a recommended disinfectant and bactericide for treating gill diseases and vibriosis in the greenfin horse-faced filefish Thamnaconus septentrionalis. However, its cumulative effect, toxic molecular mechanism and relevant signal transduction/metabolic networks in marine fishes are largely unknown.RESULTS: We employed a multi-omics approach to investigate the detrimental effects of 50 mg/L H2O2 exposure (2 h/d) on filefish for 2 d, 4 d, and 6 d. Transcriptome sequencing showed that differentially expressed genes (DEGs) were mainly classified into functions such as signal transduction, nervous system, liver and bile acid metabolism, energy metabolism, cell adhesion and communication, inflammation and immune response. Metabolomic analysis found that the significantly changed metabolites (SCMs) were involved in phenylalanine metabolism, inflammatory mediator regulation, linoleic acid metabolism, and necroptosis. The main SCMs were cholic acid, carnitine C12:1, dimethylmalonic acid, glutamic acid, L-lactic acid, shikimic acid, 2-methylsuccinic acid, and others. Moreover, H2O2-induced oxidative stress also disturbs the balance of the gut microbiota, altering the microbial composition and affecting digestive processes.CONCLUSIONS: Integrated multiomics analysis revealed that H2O2-induced detrimental impacts include mucosal damage, inflammatory and immune responses, altered energy metabolism, and gut microbiota disorders. These findings offer novel insights into the harmful effects and signal transduction/metabolic pathways triggered by H2O2 exposure in marine fishes.PMID:39434036 | DOI:10.1186/s12864-024-10903-0

EMBO J. 2024 Oct 21. doi: 10.1038/s44318-024-00269-0. Online ahead of print.ABSTRACTThe mevalonate pathway produces essential lipid metabolites such as cholesterol. Although this pathway is negatively regulated by metabolic intermediates, little is known of the metabolites that positively regulate its activity. We found that the amino acid glutamine is required to activate the mevalonate pathway. Glutamine starvation inhibited cholesterol synthesis and blocked transcription of the mevalonate pathway-even in the presence of glutamine derivatives such as ammonia and α-ketoglutarate. We pinpointed this glutamine-dependent effect to a loss in the ER-to-Golgi trafficking of SCAP that licenses the activation of SREBP2, the major transcriptional regulator of cholesterol synthesis. Both enforced Golgi-to-ER retro-translocation and the expression of a nuclear SREBP2 rescued mevalonate pathway activity during glutamine starvation. In a cell model of impaired mitochondrial respiration in which glutamine uptake is enhanced, SREBP2 activation and cellular cholesterol were increased. Thus, the mevalonate pathway senses and is activated by glutamine at a previously uncharacterized step, and the modulation of glutamine synthesis may be a strategy to regulate cholesterol levels in pathophysiological conditions.PMID:39433901 | DOI:10.1038/s44318-024-00269-0

Nat Commun. 2024 Oct 21;15(1):9063. doi: 10.1038/s41467-024-53127-2.ABSTRACTCaloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.PMID:39433757 | DOI:10.1038/s41467-024-53127-2

Food Chem. 2024 Oct 15:141649. doi: 10.1016/j.foodchem.2024.141649. Online ahead of print.ABSTRACTThroughout the natural aging process from new to aged white tea, the flavor evolves into a 'stale flavor', despite the initial umami diminishes. The flowering process, inoculation of Eurotium cristatum to white tea, improves the flavor. The impact on sensory qualities and underlying chemical basis of flowering in aged white tea warrant investigation. Sensory analysis, non-targeted metabolomics and volatilomics together deciphered flavor modifications of flowering in aged white tea from different aging years (FAWTs). Findings indicate the flowering process can recover the umami of aged white tea, enhancing the 'stale flavor'. These changes primarily stem from oxidations of catechins and free amino acids, enrichments of flavonols and soluble sugars, and 16 pivotal aroma compounds from degradations of lipids and glycosides. Additionally, 15 volatile and 39 non-volatile compounds were identified as potential biomarkers for FAWTs. These findings offer a viable strategy to improving the quality of aged white tea.PMID:39433449 | DOI:10.1016/j.foodchem.2024.141649

Clin Chim Acta. 2024 Oct 19:120010. doi: 10.1016/j.cca.2024.120010. Online ahead of print.ABSTRACTBACKGROUND: Plasma and extracellular vesicles (EVs) derived from plasma are important sources of information regarding individual health. Metabolomic analysis of plasma and EVs may provide new methods for predicting disease occurrence. This study aims to analyze the metabolomic characteristics of plasma and plasma EVs in asthma patients.METHODS: Plasma samples were collected from healthy individuals and asthma patients. EVs were isolated from the plasma using ultracentrifugation. The isolated EVs were characterized by nanoparticle tracking analysis and flow cytometry. Metabolomic analysis was performed using a liquid chromatography-mass spectrometry platform.RESULTS: This study successfully extracted EVs from plasma samples. Metabolomic analysis revealed that the composition of differential metabolites in the plasma and EVs of asthma patients was similar. KEGG pathway analysis indicated that the number of upregulated metabolic pathways enriched with differential metabolites in the plasma EVs of asthma patients was significantly greater than that in the plasma samples. Pathways associated with the onset of asthma included asthma, systemic lupus erythematosus, glycerophospholipid metabolism, and autophagy - other, primarily involving the following five metabolites: PS(18:1(9Z)/18:2(9Z,12Z)), PC(18:1(9Z)e/2:0), PS(24:1(15Z)/22:2(13Z,16Z)), PE(22:4(7Z,10Z,13Z,16Z)/22:5(4Z,7Z,10Z,13Z,16Z)), and PE(16:0/20:3(8Z,11Z,14Z)). Receiver operating characteristic analysis results suggested that these five differential metabolites may serve as potential biomarkers for asthma.CONCLUSION: We identified the metabolic characteristics of plasma and EVs in asthma patients, confirming that the metabolites in plasma EVs may serve as potential biomarkers for asthma. This finding not only enhances our understanding of the pathogenesis of asthma but also opens new avenues for targeted therapy.PMID:39433232 | DOI:10.1016/j.cca.2024.120010

J Ethnopharmacol. 2024 Oct 19:118977. doi: 10.1016/j.jep.2024.118977. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Hyperuricemia is a chronic condition characterized by persistently elevated uric acid levels, often leading to gouty arthritis and renal insufficiency. Poria cocos F.A.Wolf, a traditional Chinese medicinal herb, possesses notable diuretic and anti-inflammatory properties and is widely used to treat edema, inflammation, viral infections, and tumors. Recent studies suggest that Poria cocos has the potential to lower uric acid levels and mitigate kidney damage, making it a promising candidate for hyperuricemia treatment. However, its pharmacological mechanisms require further exploration.AIM OF THE STUDY: This study aims to elucidate the mechanisms by which Poria cocos alleviates hyperuricemia, using metabolomics and network pharmacology approaches.MATERIALS AND METHODS: Hyperuricemia was induced in rats via a high-yeast diet combined with potassium oxonate. The effects of Poria cocos were assessed by measuring serum uric acid, creatinine, urea nitrogen levels, hepatic xanthine oxidase activity, and renal tissue morphology. Non-targeted metabolomics was employed to identify differential metabolites and explore the metabolic pathways involved in its therapeutic effects. Network pharmacology was utilized to analyze potential targets and signaling pathways, which were validated through molecular docking and ELISA analysis.RESULTS: Poria cocos extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels, inhibited xanthine oxidase activity, and attenuated kidney damage. Metabolomics combined with network pharmacology identified xanthine dehydrogenase and fatty acid synthase as key targets, while purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis were identified as critical pathways. ELISA confirmed that Poria cocos suppressed xanthine dehydrogenase and fatty acid synthase expression in hyperuricemic rats. Molecular docking further verified strong binding interactions between core compounds and key targets.CONCLUSIONS: Poria cocos alleviates hyperuricemia by modulating multiple compounds, targets, and pathways. Through network pharmacology and metabolomics, it reveals that Poria cocos selectively regulates xanthine dehydrogenase and fatty acid synthase, influencing purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis pathways. These findings provide insights into its therapeutic mechanisms, supporting the clinical application of Poria cocos in treating metabolic disorders and kidney damage associated with hyperuricemia.PMID:39433165 | DOI:10.1016/j.jep.2024.118977

J Ethnopharmacol. 2024 Oct 19:118970. doi: 10.1016/j.jep.2024.118970. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Benign prostatic hyperplasia (BPH) is the most common urogenital disease in men with no definitive treatment. Inflammation, androgen imbalance, and oxidative stress play crucial roles in the pathogenesis of BPH. The flower of Hosta plantaginea (Lam.) Ascher is a pivotal medicinal plant in China, used to treat BPH. However, its effect and mechanism against BPH have not been clear.AIM OF THE STUDY: Our aim was to decipher the pharmacodynamics and mechanisms of H. plantaginea flower against BPH.MATERIALS AND METHODS: The extract yields and HPLC-based chemoprofile of ethanolic extract (HP) and total flavonoid (TF) of H. plantaginea flowers were used as reference standard to ensure their quality. The testosterone propionate-induced BPH rat model was used to assess the effects of HP and TF. Protein expression, metabolomics, and network pharmacology analyses were performed.RESULTS: Twenty constituents were identified in both HP and TF, with four quantitatively analyzed using the HPLC method. HP and TF demonstrated significant therapeutic effects on BPH, including reduced prostate size and prostatic index, improved pathological injury of prostate, as well as increased levels of testosterone, superoxide dismutase, glutathione, and glutathione peroxidase, along with decreased levels of dihydrotestosterone, 5 alpha-reductase, epidermal growth factor, TNF-α, IL-1β, IL-6, and malondialdehyde. Western blotting assay indicated that HP and TF prominently inhibited the protein expression of phosphorylated p65, IκBα, JNK, p38, Erk1/2, JAK1, STAT3, PI3K, Akt, and AMPKα1 in a dose-dependent manner. Integrating metabolomics and network pharmacology analyses revealed that HP and TF observably regulated 30 differential metabolites and 11 hub genes across the aforementioned pathways, which are closely associated with amino acid metabolism.CONCLUSION: The proposed comprehensive strategy of in vivo experiments, metabolomics, and network pharmacology studies has demonstrated that HP and TF could alleviate BPH injury in rats by suppressing inflammation, androgen imbalance, oxidative stress, and amino acid metabolism through the inhibition of NF-κB, MAPK, JAK-STAT, PI3K-Akt, and AMPK pathways, which provides novel insights into the potential of H. plantaginea flower as a treatment for BPH.PMID:39433163 | DOI:10.1016/j.jep.2024.118970

Food Chem. 2024 Oct 15;464(Pt 1):141650. doi: 10.1016/j.foodchem.2024.141650. Online ahead of print.ABSTRACTIn this study, we employ both targeted and untargeted approaches to explore the metabolomic profiles of Vanilla spp., with a particular focus on V. cribbiana (VCR) and its comparison with V. planifolia (VP). We also examine V. bahiana and V. chamissonis using targeted approaches. Through advanced analytical techniques, our untargeted LC-HRMS approach led to the annotation of 60 metabolites, revealing a complex chemical composition with 34 novel compounds in the Vanilla genus in VCR and VP. These findings highlight significant flavoring compounds and lay the foundation for a subsequent quantitative estimation approach. Our targeted analysis, which measured key molecules, underscores VCR's potential in producing vanillin and acetovanillone at levels comparable to the commercially valuable VP and even higher levels of vanillic acid. This research enriches our understanding of flavor composition in vanilla species and emphasizes the importance of exploring wild relatives of vanilla crop for sustainable production and biodiversity conservation.PMID:39432966 | DOI:10.1016/j.foodchem.2024.141650

J Anim Sci. 2024 Oct 21:skae322. doi: 10.1093/jas/skae322. Online ahead of print.ABSTRACTIn the commercial swine farm setting, the post-weaning period is a critical window during which piglets are highly susceptible to infection and enterotoxigenic E. coli (ETEC)-associated diarrhea. Short chain fatty acids and their glycerides are compounds which may influence intestinal health; however, valerate is one that has not been well-characterized for its role as a dietary supplement. Therefore, the major objective of this experiment was to investigate two forms of valerate glycerides on diarrhea, intestinal physiology, and systemic immunity of weaned pigs experimentally infected with ETEC F18. Dietary treatments included a control diet and three additional diets supplemented with 0.075% monovalerin, 0.1% monovalerin, or 0.1% trivalerin, respectively. Piglets were weaned (21-24 d of age), individually housed, and experimental diets were fed throught the 28-day trial period. After a seven-day period, all piglets were inoculated on three consecutive days with 1010 CFU ETEC F18/3 mL. Growth performance was monitored throughout the trial and daily diarrhea scores were recorded. Rectal swabs were collected for bacterial culture to confirm the presence or absence of β-hemolytic coliforms throughout the trial. Serum samples were collected and analyzed for inflammatory biomarkers on d 0, 3, 6, and 21 post-inoculation (PI) and untargeted metabolomics on d 6 PI. Intestinal mucosa and tissue sections were harvested from pigs sacrificed on d 7 PI for gene expression and histology analysis. All data, except for frequency of diarrhea and metabolomics, were analyzed by ANOVA using the PROC MIXED of SAS. Dietary trivalerin reduced (P < 0.05) the frequency of severe diarrhea over the entire trial period and the frequency of β-hemolytic coliforms on d 7 PI compared with control. The intestinal villus height on d 7 PI in jejunum tissue was increased (P < 0.05) in pigs fed trivalerin. The mRNA expression of TNF-α was decreased (P < 0.05) in the trivalerin group, while that of ZO1 was increased (P < 0.05) compared with control. Throughout the trial, serum TNF-α was reduced in pigs fed trivalerin compared with control. Serum metabolites, adenosine, inosine, and shikimic acid were reduced (P < 0.05) on d 6 PI in all treatment groups compared with control. In conclusion, the present results indicate supplementing dietary valerate glycerides exhibited beneficial impacts on diarrhea, inflammation, and intestinal gene expression of piglets during the post-weaning period.PMID:39432563 | DOI:10.1093/jas/skae322