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BACKGROUND: Diffuse gliomas are among the most common brain tumors in adults and are associated with a dismal prognosis, especially in patients with glioblastoma. To date, tumor tissue acquisition is mandatory for conclusive diagnosis and therapeutic decision-making. In this study, we aimed to identify possible diagnostic and prognostic biomarkers in cerebrospinal fluid (CSF) and blood. METHODS: During glioma surgery at our institution, CSF and blood samples were collected from patients. Subsequently, targeted metabolomics analysis was used to detect and quantify circulating metabolites. The metabolome profiles of glioma patients were compared with those of patients in a control group who had undergone neurosurgery for other entities, such as nonglial tumors or hydrocephalus, and were correlated with established glioma diagnostic molecular markers. RESULTS: In this study, a total of 30 glioma patients were included, along with a control group of 21 patients without glioma. Serum metabolomic analysis did not detect any significant differences between the groups, whereas CSF-metabolome analysis revealed increased levels of six metabolites in glioma patients. Among these, the most pronounced differences were found for the biogenic amine putrescine (p = 0.00005). p-Cresol sulfate was identified as a potential CSF marker for determining isocitrate dehydrogenase (IDH) status in glioma patients (p = 0.0037). CONCLUSION: CSF-metabolome profiling, unlike blood profiling, shows promise as a diagnostic tool for glioma patients with the potential to assign molecular subtypes. The next step will involve a larger multicenter study to validate these findings, with the ultimate objective of integrating CSF metabolomics analysis into clinical practice.

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The distinct chemical structure of thiourea derivatives provides them with an advantage in selectively targeting cancer cells. In our previous study, we selected the most potent compounds, 2 and 8, with 3,4-dichloro- and 3-trifluoromethylphenyl substituents, respectively, across colorectal (SW480 and SW620), prostate (PC3), and leukemia (K-562) cancer cell lines, as well as non-tumor HaCaT cells. Our research has demonstrated their anticancer potential by targeting key molecular pathways involved in cancer progression, including caspase 3/7 activation, NF-κB (Nuclear Factor Kappa-light-chain-enhancer of activated B cells) activation decrease, VEGF (Vascular Endothelial Growth Factor) secretion, ROS (Reactive Oxygen Species) production, and metabolite profile alterations. Notably, these processes exhibited no significant alterations in HaCaT cells. The effectiveness of the studied compounds was also tested on spheroids (3D culture). Both derivatives 2 and 8 increased caspase activity, decreased ROS production and NF-κB activation, and suppressed the release of VEGF in cancer cells. Metabolomic analysis revealed intriguing shifts in cancer cell metabolic profiles, particularly in lipids and pyrimidines metabolism. Assessment of cell viability in 3D spheroids showed that SW620 cells exhibited better sensitivity to compound 2 than 8. In summary, structural modifications of the thiourea terminal components, particularly dihalogenophenyl derivative 2 and para-substituted analog 8, demonstrate their potential as anticancer agents while preserving safety for normal cells.

Asunto(s)

Antineoplásicos , FN-kappa B , Especies Reactivas de Oxígeno , Tiourea , Factor A de Crecimiento Endotelial Vascular , Humanos , Tiourea/farmacología , Tiourea/análogos & derivados , Antineoplásicos/farmacología , Antineoplásicos/química , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Línea Celular Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismo , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Caspasa 7/metabolismo , Caspasa 3/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Relación Estructura-Actividad

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INTRODUCTION: Bovine milk contains a rich matrix of nutrients such as carbohydrates, fat, protein and various vitamins and minerals, the composition of which is altered by factors including dietary regime. OBJECTIVES: The objective of this research was to investigate the impact of dietary regime on the metabolite composition of bovine whole milk powder and buttermilk. METHODS: Bovine whole milk powder and buttermilk samples were obtained from spring-calving cows, consuming one of three diets. Group 1 grazed outdoors on perennial ryegrass which was supplemented with 5% concentrates; group 2 were maintained indoors and consumed a total mixed ration diet; and group 3 consumed a partial mixed ration diet consisting of perennial ryegrass during the day and total mixed ration maintained indoors at night. RESULTS: Metabolomic analysis of the whole milk powder (N = 27) and buttermilk (N = 29) samples was preformed using liquid chromatography-tandem mass spectrometry, with 504 and 134 metabolites identified in the samples respectively. In whole milk powder samples, a total of 174 metabolites from various compound classes were significantly different across dietary regimes (FDR adjusted p-value ≤ 0.05), including triglycerides, of which 66% had their highest levels in pasture-fed samples. Triglycerides with highest levels in pasture-fed samples were predominantly polyunsaturated with high total carbon number. Regarding buttermilk samples, metabolites significantly different across dietary regimes included phospholipids, sphingomyelins and an acylcarnitine. CONCLUSION: In conclusion the results reveal a significant impact of a pasture-fed dietary regime on the metabolite composition of bovine dairy products, with a particular impact on lipid compound classes.

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Alimentación Animal , Suero de Mantequilla , Metabolómica , Leche , Animales , Bovinos/metabolismo , Leche/química , Leche/metabolismo , Metabolómica/métodos , Suero de Mantequilla/análisis , Alimentación Animal/análisis , Dieta/veterinaria , Polvos , Metaboloma , Espectrometría de Masas en Tándem , Femenino , Cromatografía Liquida/métodos

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Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation.

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Antiinflamatorios , Bacterias , Colitis Ulcerosa , Sulfato de Dextran , Microbioma Gastrointestinal , Phyllanthus emblica , Extractos Vegetales , Polisacáridos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Sulfato de Dextran/efectos adversos , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/administración & dosificación , Polisacáridos/aislamiento & purificación , Phyllanthus emblica/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/administración & dosificación , Masculino , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/metabolismo , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/efectos de los fármacos , Bacterias/genética , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Ratones Endogámicos C57BL , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis/microbiología , Modelos Animales de Enfermedad , Colon/microbiología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/inmunología

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OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

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Metabolómica , Humanos , Metabolómica/métodos , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/metabolismo , Neoplasias Gástricas/sangre , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/diagnóstico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Neoplasias Gastrointestinales/sangre , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/diagnóstico , Metaboloma/fisiología , Estudios de Casos y Controles , Unión Esofagogástrica/patología , Unión Esofagogástrica/metabolismo

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We aimed to elucidate the toxic effects and biological activities of 3-phenoxybenzoic acid (3PBA) and its metabolite products.Numerous in silico methods were used to identify the toxic effects and biological activities of 3PBA, including PASS online, molecular docking, ADMETlab 2.0, ADMESWISS, MetaTox, and molecular dynamic simulation.Ten metabolite products were identified via Phase II reactions (O-glucuronidation, O-sulfation, and methylation).All of the investigated compounds were followed by Lipinski's rule, indicating that they were stimulants or inducers of hazardous processes.Because of their high gastrointestinal absorption and ability to reach the blood-brain barrier, the studied compounds' physicochemical and pharmacokinetic properties matched existing evidence of harmful effects, including haematemesis, reproductive dysfunction, allergic dermatitis, toxic respiration, and neurotoxicity.The studied compounds have been linked to the apoptotic pathway, the reproductivity system, neuroendocrine disruptors, phospholipid-translocating ATPase inhibitors, and JAK2 expression.An O-glucuronidation metabolite product demonstrated higher binding affinity and interaction with CYP2C9, CYP3A4, caspase 3, and caspase 8 than 3PBA and other metabolite products, whereas metabolite products from methylation were predominant and more toxic.Our in silico findings partly meet the 3Rs principle by minimizing animal testing before more study is needed to identify the detrimental effects of 3PBA on other organs (liver, kidneys).Future research directions may involve experimental validation of in silico predictions, elucidation of molecular mechanisms, and exploration of therapeutic interventions.These findings contribute to our understanding of the toxicological profile of 3PBA and its metabolites, which has implications for risk assessment and regulatory decisions.

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Key properties & pharmacokinetics of 3PBA & its metabolites were reportedMetabolite products from methylation were predominant and more toxicMain toxics: haematemesis, reproductive dysfunction, toxic respiration, dermatitis.

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Benzoatos , Simulación por Computador , Benzoatos/química , Benzoatos/metabolismo , Benzoatos/toxicidad , Modelos Moleculares , Conformación Molecular , Fenómenos Químicos , Caspasa 3/química , Caspasa 3/metabolismo , Caspasa 8/química , Caspasa 8/metabolismo , Sitios de Unión de Anticuerpos , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo

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The Cannabis species is one of the potent ancient medicinal plants acclaimed for its medicinal properties and recreational purposes. The plant parts are used and exploited all over the world for several agricultural and industrial applications. For many years Cannabis spp. has proven to present a highly diverse metabolomic profile with a pool of bioactive metabolites used for numerous pharmacological purposes ranging from anti-inflammatory to antimicrobial. Cannabis sativa has since been an extensive subject of investigation, monopolizing the research. Hence, there are fewer studies with a comprehensive understanding of the composition of bioactive metabolites grown in different environmental conditions, especially C. indica and a few other Cannabis strains. These pharmacological properties are mostly attributed to a few phytocannabinoids and some phytochemicals such as terpenoids or essential oils which have been tested for antimicrobial properties. Many other discovered compounds are yet to be tested for antimicrobial properties. These phytochemicals have a series of useful properties including anti-insecticidal, anti-acaricidal, anti-nematicidal, anti-bacterial, anti-fungal, and anti-viral properties. Research studies have reported excellent antibacterial activity against Gram-positive and Gram-negative multidrug-resistant bacteria as well as methicillin-resistant Staphylococcus aureus (MRSA). Although there has been an extensive investigation on the antimicrobial properties of Cannabis, the antimicrobial properties of Cannabis on phytopathogens and aquatic animal pathogens, mostly those affecting fish, remain under-researched. Therefore, the current review intends to investigate the existing body of research on metabolomic profile and anti-microbial properties whilst trying to expand the scope of the properties of the Cannabis plant to benefit the health of other animal species and plant crops, particularly in agriculture.

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BACKGROUND: The metabolites produced from choline contribute to atherosclerosis (AS) pathogenesis, and the gut microbiota is redundantly essential for this process. Indole-3-carbinol (I3C), found in cruciferous vegetables such as broccoli, cabbage, cauliflower and brussels sprouts, helps prevent hyperlipidemia, maintain the gut microbiota balance, and decrease the production of trimethylamine-N-oxide (TMAO) from choline in the diet. PURPOSE: The objective of this research was to investigate the impact of I3C on choline-induced AS and to further elucidate the underlying mechanism involved. METHODS: AS models of high-choline-induced ApoE-/- mice and TMAO-promoted foamy macrophages were established to observe the effect of I3C on the formation of atherosclerotic plaques and foam cells and changes in AS-related indicators (including blood biochemical indicators, TMA, TMAO, SRA, and SRB1), and integrated analyses of the microbiome and metabolome were used to reveal the mechanism of action of I3C. RESULTS: We found that I3C inhibited high-choline-induced atheroma formation (50-100 mg/kg/d, in vivo) and slightly improved the lipid profile (15 mg/kg/d, in vivo). Moreover, I3C suppressed lipid influx at a concentration of 40 µmol/L in vitro, enhanced the diversity of the gut microbiota and the abundance of the phylum Verrucomicrobia, and consequently modified the gut microbial metabolites at a dosage of 50 mg/kg/d in the mice. Associative analyses based on microbiome and metabolomics revealed that 1-methyladenosine was a key modulator of the protective effect of I3C against AS in high-choline-induced ApoE-/- mice. CONCLUSION: These findings demonstrate for the first time that I3C ameliorates AS progression through remodeling of the gut microbiome and metabolomics, which paves the way for the possible therapeutic use of this vegetable-derived natural compound and may reduce the clinical severity of AS-related cardiovascular diseases.

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Aterosclerosis , Colina , Microbioma Gastrointestinal , Indoles , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Colina/farmacología , Indoles/farmacología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Ratones , Masculino , Apolipoproteínas E , Metilaminas/metabolismo , Metilaminas/farmacología , Ratones Endogámicos C57BL , Metabolómica , Metaboloma/efectos de los fármacos , Placa Aterosclerótica/tratamiento farmacológico

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Culex pipiens (Linnaeus, 1758) mosquitoes search plant sources of sugars to cope with the energetic demand of various physiological processes. The crop as part of the digestive system is devoted to the storage of sugar-based meal obtained from various nectars sources. The profiling of sugars and metabolites in the Culex pipiens' crop is scarce, and only few studies used Liquid Chromatography - Mass Spectrometry (LC-MS), which provides broad detection for biomonitoring environmental substances and even contaminants in the sugar diet of mosquitoes populations. Therefore, sugar and metabolite profiling were performed on crops obtained from mosquitoes exposed to plant nectar under laboratory or natural conditions by Ultra High-Performance LC-MS (UHPLC-MS). This method allowed us a precise quantitative and qualitative identification of sugar diet and associated environmental compounds in the crop of the mosquito C. pipiens. Under laboratory condition, mosquitoes were allowed to feed on either glucose solution, commercially-available flowers or field collected flowers. In addition, we collected mosquitoes from the field to compare those crop metabolomes with metabolome patterns occurring after nectar feeding in the lab. The sugar quantities and quality obtained from the crops of mosquitoes collected in the field were similar to those crops obtained from mosquitoes that fed on commercially-available flowers and from field collected flowers with a limit of detection of 10 µg/L for sucrose, glucose and sucrose. Next to sugar compounds, we identified 2 types of amino acids, 12 natural products, and 9 pesticides. Next to the diversity of sugar compounds, we could confirm that secondary metabolites and environmental pollutants are typically up taken from floral nectar sources by C. pipiens. The in-depth knowledge on mosquito-plant interactions may inspire the development and further optimization of mosquito trap systems and arboviral surveillance systems.

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BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed. METHODS: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post-HA and TPE sessions on days 7 and 14 using high-resolution mass spectrometry. RESULTS: The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p < .05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine-proline metabolism (6 metabolites) and microbial metabolism respectively (p < .05). Metabolites linked to taurine-hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post-TPE therapy (p < .05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post-HA therapy compared to TPE and SMT (p < .05). Higher baseline plasma level of 11-deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p < .05) and mortality (log-rank-p < .05). Notably, 51 of the 64 metabolite signatures (ACLF non-survivor) were reversed post-HA treatment compared to TPE and SMT(p < .05). CONCLUSION: HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11-deoxycorticosterone level correlates with early mortality in ACLF patients.

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Insuficiencia Hepática Crónica Agudizada , Hemoperfusión , Humanos , Adsorción , Triptófano , Metaboloma , Ácidos y Sales Biliares , Desoxicorticosterona

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ETHNOPHARMACOLOGICAL RELEVANCE: The Zishen Yutai pills (ZYP), a Chinese medicinal formulation derived from the Qing Dynasty prescription "Shou Tai pills", have been documented to exhibit beneficial effects in clinical observations treating premature ovarian failure (POF). However, the anti-POF effects and its comprehensive systemic mechanism have not yet been clarified. AIM OF THE REVIEW: Therapeutic effects and systemic mechanism of ZYP in POF were evaluated. MATERIALS AND METHODS: After pulverization, sieving, and stirring, ZYP was administered intragastrically to cisplatin-induced POF mice at a dose of 1.95 mg/kg/d for 14 days. The anti-POF effects of ZYP were investigated by assessing the number of ovarian follicles at different developmental stages, as well as measuring serum estradiol (E2) levels and ovarian-expressed anti-Müllerian hormone (AMH). Reproductive performance and offspring health were evaluated to predict fertility restoration. Furthermore, a combination of proteomic and metabolomic profiling was employed to elucidate the underlying molecular mechanism of ZYP in treating POF. Western blot (WB) analyses and real-time quantitative polymerase chain reaction (RT-qPCR) were conducted to explore the mechanisms through which ZYP exerted its anti-POF effects. RESULTS: We have demonstrated that oral administration of ZYP reversed the reduction in follicles at different developmental stages and stimulated the expressions of serum E2 and ovarian-expressed AMH in a cisplatin-induced POF model. Additionally, ZYP ameliorated follicle apoptosis in ovaries affected by cisplatin-induced POF. Furthermore, treatment with ZYP restored the quantity and quality of oocytes, as well as enhanced fertility. Our results revealed 62 differentially expressed proteins (DEPs) through proteomic analyses and identified 26 differentially expressed metabolites (DEMs) through metabolomic analyses. Both DEPs and DEMs were highly enriched in the arachidonic acid (AA) metabolism pathway. ZYP treatment effectively upregulated the protein and mRNA expression of critical targets in AA metabolism and the AKT pathway, including CYP17α1, HSD3ß1, LHR, STAR, and AKT, in cisplatin-induced POF mice. CONCLUSIONS: These results indicated that ZYP exerted protective effects against POF and restored fertility from cisplatin-induced apoptosis. ZYP could be a satisfying alternative treating POF.

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Medicamentos Herbarios Chinos , Menopausia Prematura , Insuficiencia Ovárica Primaria , Femenino , Humanos , Ratones , Animales , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Insuficiencia Ovárica Primaria/metabolismo , Ácido Araquidónico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Cisplatino/efectos adversos , Proteómica , Fertilidad , Hormona Antimülleriana

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive cartilage and bone erosion. This work aimed to evaluate the metabolomic profile of Medicago sativa L. (MS) (alfalfa) seeds and explore its therapeutic impact against RA in rats. Arthritis was induced by complete Freund's adjuvant (CFA) and its severity was assessed by the arthritis index. Treatment with MS seeds butanol fraction and interlukin-1 receptor antagonist (IL-1RA) were evaluated through measuring interlukin-1 receptor (IL-1R) type 1 gene expression, interlukin-1 beta (IL-1ß), oxidative stress markers, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), caspase-3 (Cas-3), intracellular adhesion molecule-1 (ICAM-1), DNA fragmentation, and chromosomal damage. Total phenolics/ flavonoids content in the ethyl acetate, butanol fraction and crude extract of MS seeds were estimated. The major identified compounds were Quercetin, Trans-taxifolin, Gallic acid, 7,4'-Dihydroxyflavone, Cinnamic acid, Kudzusaponin SA4, Isorhamnetin 3-O-beta-D-2'',3'',4''-triacetylglucopyranoside, Apigenin, 5,7,4'-Trihydroxy-3'-methoxyflavone, Desmethylxanthohumol, Pantothenic acid, Soyasapogenol E, Malvidin, Helilandin B, Stigmasterol, and Wairol. Treatment with MS seeds butanol fraction and IL-1RA enhanced all the biochemical parameters and the histopathological features of the ankle joint. In conclusion, Trans-taxifolin was isolated for the first time from the genus Medicago. MS butanol fraction seeds extract and IL-1 RA were considered as anti-rheumatic agents.

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Artritis Experimental , Artritis Reumatoide , Ratas , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Medicago sativa/metabolismo , Antiinflamatorios/farmacología , Fitoterapia , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/uso terapéutico , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Interleucinas/metabolismo , Interleucinas/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Estrés Oxidativo , Butanoles , Citocinas/metabolismo

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"Sulmona Red Garlic" is a well-known Italian traditional product. Bulbs, used for culinary purposes, have been largely investigated for their medicinal properties whereas aerial bulbils are usually removed as waste material. Here, for the first time, chemical composition and biological properties of the hydroalcoholic extract from aerial bulbils were investigated. Complementary information on metabolite composition were obtained using both NMR based untargeted and HPLC-DAD targeted methodologies. The NMR analysis revealed the presence of sugars, organic acids, amino acids, organosulphur compounds (methiin, alliin, allicin and cycloalliin), and other secondary metabolites. In particular, methiin and alliin were identified for the first time in the NMR spectra of aerial bulbil garlic extracts. Polyphenol content was determined by HPLC-DAD analysis: catechin, chlorogenic acid, and gallic acid turned out to be the most abundant phenolics. Hydroalcoholic extract blocked cell proliferation of colon cancer cell line HCT116 with an IC50 of 352.07 µg/mL, while it was non-toxic to myoblast cell line C2C12. In addition, it caused seedling germination reduction of two edible and herbaceous dicotyledon species, namely Cichorium intybus and C. endivia. Moreover, the same extract reduced the gene expression of TNF-α (tumor necrosis factor), HIF1-α (hypoxia-inducible factor), VEGFA (vascular endothelial growth factor), and transient receptor potential (TRP) M8 (TRPM8) indicating the ability to contrast cancer development through the angiogenic pathway. Final, in silico experiments were also carried out supporting the biological effects of organosulphur compounds, particularly alliin, which may directly interact with TRPM8. The results here reported suggest the potential use of garlic aerial bulbils often considered a waste product as a source in phytotherapeutic remedies.

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Neoplasias del Colon , Ajo , Ajo/química , Ecotipo , Factor A de Crecimiento Endotelial Vascular/genética , Extractos Vegetales/farmacología , Antioxidantes , Compuestos de Azufre/farmacología , Compuestos de Azufre/análisis , Neoplasias del Colon/patología

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Mung bean (Vigna radiata (L.) Wilczek) sprouts are popular over the world because of their taste, nutritional value, well-balanced biochemical composition, and other properties beneficial for human health. Germination conditions affect the composition of metabolites in mung bean sprouts, so a detailed study into its variability is required. This article presents the results of a comparison of the metabolite composition in the leaves of mung bean sprouts germinated first in the dark (DS) and then in the light (LS). Gas chromatography with mass spectrometry (GC-MS) made it possible to identify more than 100 compounds representing various groups of phytochemicals. Alcohols, amino acids, and saccharides predominated in the total amount of compounds. The analysis of metabolomic profiles exposed a fairly high intra- and intervarietal variability in the metabolite content. DS and LS differed in the qualitative and quantitative content of the identified compounds. The intravarietal variability was more pronounced in DS than in LS. DS demonstrated higher levels of saccharides, fatty acids, acylglycerols, and phenolic compounds, while amino acids were higher in LS. Changes were recorded in the quantitative content of metabolites participating in the response of plants to stressors-ornithine, proline, GABA, inositol derivatives, etc. The changes were probably induced by the stress experienced by the sprouts when they were transferred from shade to light. The analysis of variance and principal factor analysis showed the statistically significant effect of germination conditions on the content of individual compounds in leaves. The identified features of metabolite variability in mung bean genotypes grown under different conditions will contribute to more accurate selection of an illumination pattern to obtain sprouts with desirable biochemical compositions for use in various diets and products with high nutritional value.

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By-products from plant sources are recently regarded as a valuable source of bioactive compounds. In this regard, the present study aims to assess the bioactivities of the 70 % MeOH extract obtained from Vicia faba peels and analyze its metabolomic profile. Acetylcholinesterase and carbohydrate metabolizing enzymes inhibitory activities of the plant extract were assayed using quantitative colorimetric tests. Antioxidant activity was estimated by DPPH assay, and cytotoxic activity was evaluated against normal fibroblast skin cells (1-BJ1). Ninety-one metabolites were tentatively identified using ultra-high-performance liquid chromatography (UHPLC) hyphenated with quadrupole-time-of-flight tandem mass spectrometry (QTOF-MS). Most of these compounds were described for the first time in the plant. In addition, catechin, rutin, quercitrin, and rhamnetin were isolated from the plant extract. The plant extract and the isolated compounds possessed no cytotoxic activity on (1-BJ1), while they exhibited anticholinesterase with the highest activity for 70 % MeOH extract (IC50 =120.11 mg/L), antioxidant potential with the highest activity for rutin (90.54±0.73 %), and carbohydrate metabolizing inhibitory activities with the highest activity for rutin. These discoveries imply that V. faba peels might serve as an efficient antioxidant, exhibit anticholinesterase properties, and have the potential for use in managing diabetes, all while avoiding cytotoxicity in normal cells.

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Fabaceae , Vicia faba , Vicia faba/química , Antioxidantes/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Acetilcolinesterasa , Extractos Vegetales/farmacología , Extractos Vegetales/química , Rutina/farmacología , Carbohidratos

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Bactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.

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Ácido Pirúvico , Tephritidae , Animales , Drosophila , Ácidos Grasos , Hipoxia

RESUMEN

BACKGROUND: Wilson's disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson's disease patients (who exhibit similar symptoms but have normal copper levels). RESULTS: Our pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson's disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson's disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson's disease). CONCLUSIONS: Our analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD.

Asunto(s)

Degeneración Hepatolenticular , Enfermedad de Parkinson , Humanos , Femenino , Masculino , Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/genética , Cobre , Cromatografía Liquida , Espectrometría de Masas en Tándem , Cirrosis Hepática/diagnóstico

RESUMEN

Porcine epidemic diarrhea virus (PEDV) is a main cause of severe enteric disease in piglets, leading to millions of dollars lost annually in the global pig industry. Parenteral vaccination is limited in generating sufficient mucosal immunity, which is crucial for early defense against PEDV. Here, we orally administered ginseng stem-leaf saponins (GSLS) to mice before parenteral vaccination and found that GSLS significantly enhanced the phagocytosis of dendritic cells, promoted the activities of CD4+ T cells and increased PEDV-specific IgA antibodies in the intestinal mucosa. Transcriptomic results showed that the altered genes following GSLS treatment were mostly related to the immune response and metabolism. In addition, integrated analysis of the transcriptome and metabolome revealed that the mechanism by which GSLS enhances mucosal immunity may be associated with progesterone-related pathways. Further studies are needed to explore the detailed molecular mechanisms.

Asunto(s)

Infecciones por Coronavirus , Panax , Virus de la Diarrea Epidémica Porcina , Saponinas , Enfermedades de los Porcinos , Animales , Porcinos , Ratones , Inmunidad Mucosa , Transcriptoma , Saponinas/farmacología , Vacunación , Hojas de la Planta , Infecciones por Coronavirus/prevención & control

RESUMEN

The genus Cecropia is used in the traditional medicine of Tabasco, Mexico, in diabetes and hypertension treatments, mainly without distinction of the species. This contribution aimed to carry out the metabolic analysis and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy-based fingerprinting of the hydroalcoholic leaf extracts of Cecropia peltata (Cp) and Cecropia obtusifolia (Co) collected in five sub-regions of the State of Tabasco (Cp1, "Centro"; Cp2, "Chontalpa"; Cp3, "Pantanos"; Cp4, "Ríos" and Co5, "Sierra"). Firstly, the extracts were evaluated for their Total Phenol Content (TPC) and Total Flavonoid Content (TFC) by spectrophotometric methods. In addition, metabolic analysis was performed using High-Performance Liquid Chromatography with Diode-Array Detection HPLC-DAD, which allowed the quantification of the chemical markers: chlorogenic acid, isoorientin, and orientin, as well as a vitexin analog. Finally, metabolomic analysis was carried out based on the 1H-NMR spectra. The Cp4 extract (C. peltata from the "Ríos" sub-region) presented the highest values of TPC (155 ± 9.1 mg GAE/g E) and TFC (724 ± 22.2 mg RE/g E). The metabolic analysis was similar among the five samples; the highest concentrations of the four chemical markers were found in Cp3 (C. peltata from the "Pantanos" sub-region) for chlorogenic acid (39.8 ± 2.3 mg/g) and isoorientin (51.5 ± 2.9 mg/g), in Cp4 for orientin (49.9 ± 0.6 mg/g), and in Cp2 (C. peltata from the "Chontalpa" sub-region) for the vitexin analog (6.2 ± 0.2 mg/g). The metabolic analysis and the 1H-NMR fingerprint analysis showed intraspecies differences among the C. peltata samples and interspecies between C. peltata and C. obtusifolia, which were attributed to variations in the metabolite groups as well as in the proportion of sugars such as glucose and xylose.

RESUMEN

Alzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a brain disease and harms the whole-body metabolism. We analyzed 630 polar and apolar metabolites in the blood of 20 patients with AD and 20 healthy individuals, to determine whether the composition of plasma metabolites could offer additional indicators to evaluate any alterations in the metabolic pathways related to the illness. Multivariate statistical analysis showed that there were at least 25 significantly dysregulated metabolites in patients with AD compared with the controls. Two membrane lipid components, glycerophospholipids and ceramide, were upregulated, whereas glutamic acid, other phospholipids, and sphingolipids were downregulated. The data were analyzed using metabolite set enrichment analysis and pathway analysis using the KEGG library. The results showed that at least five pathways involved in the metabolism of polar compounds were dysregulated in patients with AD. Conversely, the lipid pathways did not show significant alterations. These results support the possibility of using metabolome analysis to understand alterations in the metabolic pathways related to AD pathophysiology.

Asunto(s)

Enfermedad de Alzheimer , Humanos , Anciano , Enfermedad de Alzheimer/metabolismo , Metabolómica/métodos , Metaboloma/fisiología , Espectrometría de Masas , Redes y Vías Metabólicas