Metabolite Concentrations Research Articles

Helicobacter pylori promotes intestinal flora imbalance and hepatic metabolic disorders under arsenic stress.

Environmental arsenic contamination is a serious issue that cannot be ignored, since arsenic levels in drinking water frequently exceed safety standards, and there is an increased prevalence of Helicobacter pylori (H. pylori) infection. This results in an increasing population at risk of simultaneous exposure to both harmful agents, yet whether a synergistic interaction exists between them remains unclear. Therefore, this study aims to investigate the combined effects and underlying pathogenic mechanisms of concurrent exposure to these two hazardous factors by establishing a mouse model that is infected with H. pylori and exposed to inorganic arsenic through drinking water. Analysis of intestinal flora revealed significant alterations in the composition, relative abundance (Akkermansia, Faecalibaculum, Ilieibacterium, etc.), and metabolic potential of the intestinal microflora (amino acid metabolism and energy metabolism) in the combinatory exposure group. Non-targeted metabolomics analysis identified that the combinatory exposure group exhibited greater fluctuations in metabolite content, particularly in triacylglycerol, fatty-acid, peptide and amino acid. Moreover, H. pylori infection and arsenic exposure had increased levels of metabolites associated with the intestinal microbiota in their livers (4-Ethylphenyl sulfate and Phenylacetylglycine). Further analysis revealed significant correlations between changes in the intestinal flora and alterations in liver metabolic profiles. Herein, we hypothesize that H. pylori infection may exacerbate the intestinal flora imbalance and hepatic metabolic disturbances caused by arsenic exposure, which may disrupt enterohepatic homeostasis and potentially increase biological susceptibility to heavy metal toxicity.

Continuous carbon source supply is essential for high rifamycin productivity of Amycolatopsis mediterranei in nitrate-stimulated fermentation revealed by a metabolomic study.

Amycolatopsis mediterranei U32 is an industrial strain capable of producing therapeutically useful rifamycin SV. In early days of fermentation studies, nitrate was found to increase the yield of rifamycin along with globally, affecting both carbon and nitrogen metabolism in favor of antibiotic biosynthesis; thus, the nitrate-stimulating effect (NSE) hypothesis was proposed. Although GlnR is likely the master regulator of the pleotropic effect of NSE, the global metabolism affected by NSE has never been systematically examined. In this study, we use mass spectrometry-based metabolomics to quantitatively monitor the metabolomic responses of A. mediterranei U32 to nitrate supplementation. The concentrations of many metabolites involved in central carbon metabolism, including glucose 6-phosphate, glucose 1-phosphate, UDP-glucose, and acetyl-coenzyme A, decrease significantly after the addition of 80 mM potassium nitrate to the medium. We find that the rifamycin SV production yield could be increased by the addition of glucose during the logarithmic growth phase. Moreover, at multiple time points during glucose supplementation in the mid- and late-exponential phases, the yield of rifamycin SV further increases, reaching 354.3%. Quantitative real-time PCR assays of the key genes corresponding to the synthesis of the rifamycin SV precursor combined with data from metabolomics analysis confirm that carbon source deficiency is compensated for after glucose supplementation and that the expression of genes involved in the pathway of 3-amino-5-hydroxybenzoic acid synthesis by UDP-glucose and glutamine is significantly increased. This preliminary exploration of dynamic metabolomic profiles has the potential to increase our understanding of the NSE.

Widely targeted metabolomics analysis reveals dynamic changes in metabolites of 'Hass' avocado during postharvest ripening period.

Avocado (Persea americana Mill) is a climacteric fruit harvested at the green stage that ripens postharvest to become edible. The 'Hass' cultivar, known for its rich, buttery flavor and pear-shaped appearance, was studied for metabolite changes during postharvest ripening using UPLC-MS/MS approach. The 16-day ripening period could be divided into three stages: evolution (days 1-9), edible ripe (days 10-15) and overripe (day 16). A total of 1397 metabolites were identified across 13 classes. Among them, amino acids transitioned from conjugated to free forms, while sugars converted to monosaccharides, enhancing savory and sweet tastes. The concentration of certain secondary metabolites like terpenes, coumarins, and alkaloids increased, likely supporting antimicrobial defense, alongside a substantial increase in lipid content. Additionally, 20 compounds were screened as markers for edible ripeness. This study provides valuable insights into avocado postharvest ripening and offers references for optimizing shelf-life.

Chitosan nanoparticles loaded with Lactobacillus rhamnosus bioactive metabolites: Preparation, characterization, and antifungal activity.

Aspergillus flavus is a severe danger to worldwide maize (Zea mays) cultivation, due to its extreme toxicity of aflatoxins produced by the fungi, and its ability to cause economic losses while also posing a health concern to humans and animals. Among the measures that may be considered for A. flavus control, applying coatings based on natural ingredients appears to be the most promising. The current work examines the antagonistic ability of Lactobacillus rhamnosus bioactive metabolites added to chitosan nanoparticles against A. flavus on maize kernels. The chitosan nanoparticles loaded with L. rhamnosus bioactive metabolites were characterized using the transmission electron microscope (TEM), zeta potential, size distribution, polydiversity index (PDI), pH, encapsulation efficiency and Fourier transform infrared spectroscopy (FTIR). The TEM revealed that the chitosan nanoparticles loaded with bioactive metabolites were spherical and smooth on the surface, and by increasing the concentration of bioactive metabolites added to the chitosan nanoparticles, the diameter of the chitosan nanoparticle grew. The zeta potential and size distribution values increased as the quantity of L. rhamnosus bioactive metabolites increased in the chitosan nanoparticles. The FTIR analysis indicated the presence of several functional groups, including alkynes, alkene, aliphatic primary amines, and other functional groups. The chitosan nanoparticles loaded with L. rhamnosus bioactive metabolites at a concentration of 7mg/mL showed significant antifungal activity against A. flavus, reducing their growth in maize kernels by 89.42% after 10 days of storage. They also reduced the percentage of germination inhibition rate and viability percentage. It could be concluded that adding L. rhamnosus bioactive metabolites to chitosan nanoparticles might have significant implications for food safety by using it in the industry to reduce the fungal contamination of grains.

Integrated gut microbiota and multi-omics analysis revealed the growth differences of female giant freshwater prawn (Macrobrachium rosenbergii).

Macrobrachium rosenbergii (giant freshwater prawn; GFP) holds considerable importance in aquaculture due to its high market demand and economic significance. Female GFP growth varies significantly, however, the processes responsible for these growth disparities remain unknown. In this study, intestinal and hemolymph samples of large (FL), medium (FM), and small (FS) female GFPs were collected to investigate the molecular mechanism of female GFP growth. Through the utilization of 16S rRNA sequencing and liquid chromatography-mass spectrometry metabolomics, significant intestinal flora and metabolites linked to the growth performance of female GFPs were identified. The dominant phyla of the three groups were the same, namely Firmicutes and Proteobacteria. Among groups, small females exhibited the lowest abundance of Proteobacteria (27.26%) and the highest abundance of Firmicutes (70.10%). The most abundant genus in each group was Lactococcus. Liquid chromatography-mass spectrometry identified 115 annotated differential metabolites, and essential metabolites related to female GFP growth performance were screened. The concentration of serum metabolites in the larger females exhibited a statistically significant variance compared to that of the smaller females. Through association analysis, we identified key genes, metabolites, and gut microbiota that influence the growth of female GFPs. Likewise, we used multi-omics techniques to establish two relationship models ("gut microbiota-GFP phenotype-metabolite", "gut microbiota-GFP phenotype-transcript"), and three important network association models ("DN5520_c0_g1-CW1-Bacteroides", "DN537746_c0_g1-BW-Roseburia" and "Picolinic acid-phenotype-Roseburia") were further developed. The present study provides novel insights into the mechanisms underlying the variability in individual growth among female GFPs. Our findings offer valuable information for future investigations exploring the correlation between gut flora and host organisms in aquatic environments.

Whole blood concentrations of fingolimod and its pharmacologically active metabolite fingolimod phosphate obtained during routine health care of patients with multiple sclerosis.

Fingolimod is a first-in-class, orally administered drug indicated for the treatment of relapsing-remitting multiple sclerosis. It acts as an immunomodulator, is classified as a "disease-modifying therapy", and its main mechanism of action is the modulation of sphingosine-1-phosphate receptors. In this prospective pilot study, whole blood concentrations of fingolimod and fingolimod phosphate obtained during routine health care were measured. In this study, we aimed to determine whether therapeutic monitoring of fingolimod and fingolimod phosphate concentrations can help personalise pharmacotherapy for patients with multiple sclerosis. The study group consisted of 73 patients treated with oral fingolimod (0.5 mg) once daily. Blood samples were collected between July 2021 and January 2022. The whole blood concentrations of fingolimod and fingolimod phosphate were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. The relationship between the measured concentrations and the absolute peripheral blood lymphocyte count was evaluated. Fingolimod concentrations ranged from 0.61 to 6.21 µg/L, and fingolimod phosphate concentrations from 0.48 to 4.28 µg/L. Significantly higher concentrations of the active metabolite, fingolimod phosphate, and a significantly higher fingolimod phosphate/fingolimod concentration ratio were observed in women. The sum of fingolimod and fingolimod phosphate concentrations was significantly higher in the subgroup of patients with a lower absolute peripheral blood lymphocyte count. Although all patients were treated with the same dose of fingolimod (0.5 mg orally daily), a 10-fold difference was observed in the achieved whole blood concentrations of fingolimod and fingolimod phosphate. This wide inter-individual variability may lead to potential toxicity or suboptimal concentrations, with the risk of further deterioration in the clinical condition of patients with multiple sclerosis. Therefore, fingolimod is a suitable candidate for therapeutic drug monitoring, including monitoring patient adherence to treatment.

Chemical Compounds from Seaweeds on the Tropical Coast of Brazil

Seaweeds have been explored by humans for thousands of years as a source of chemical compounds. This study describes the content of minerals, ash, carbohydrates, protein, lipids, and main metabolites of dichloromethane / methanol extracts of the seaweed Ulva lactuca, Padina gymnospora, Palisada perforata and Gelidiella acerosa from sandstone reefs on the Brazilian tropical coast (Pernambuco, Northeastern of Brazil). The content (% dry weight) of carbohydrates ranged from 14.35-48.52, proteins 7.49-14.98, total lipids 0.40-8.92, and ash 18.51-37.02. The concentration (mg kg dry algae-1) of Ca (900-3468), Mg (1655-4902), K (810-1707), Na (1062-4580), Mn (19-4462), and Cu (3.6-6.4) were maximum in Palisada and minimum in Padina. In turn, the lowest and highest contents (mg kg dry algae-1) of Fe (100-2312), Zn (18-43), and Cr (0.08-0.93) were recorded in Gelidiella and Ulva, respectively. Neophytadiene was the major compound. Phytol and palmitic acid were found in all seaweeds, although in low quantities. Palisada had the highest contents (% dry weight) of metabolites (neophytadiene: 23.89, phytol: 8.29; palmitic acid: 8.32), while Ulva had the lowest, except phytone, which was present only in this species. Our findings highlight the potential of these macroalgae from the coastal reefs as a source of chemical compounds.

ZnONPs alleviate cadmium toxicity in pepper by reducing oxidative damage.

Cadmium (Cd) is a genotoxic heavy metal causing severe toxicity symptoms in plants, which has been a major threat to worldwide crop production. Recently, nanoparticles (NPs) have been employed as a novel strategy to facilitate the Cd stress and act as nano-fertilizers directly. Therefore, this study aims to explore the effects of zinc oxide nanoparticles (ZnONPs; 15mg/L) on plant growth, photosynthetic activity, antioxidant activity and root morphology in Capsicum chinense Jacq. under Cd (CdCl2; 50μM/L) stress. The pepper plants were treated with Cd stress for 14 days, and the treatment was given directly into the hydroponic solution, while ZnONPs were applied as foliar spray two times a day (9 a.m. - 3 p.m.). The results revealed that Cd stress inhibited plant growth and biomass by impairing photosynthesis in photosystem function, gas exchange parameters, root activity, and morphology. In contrast, ZnONPs application notably reinforced the plant growth traits, increased photosynthesis efficiency in terms of chlorophyll content, SPAD index, gas exchange parameters and PSII maximum efficiency (Fv/Fm) and decreased Cd accumulation in leaf and root by 30% and 75%. Furthermore, ZnONPs efficiently restricted the hydrogen peroxide, superoxide ion (H2O2, O2•-). They restored cellular integrity (less MDA production) by triggering the antioxidant enzyme activities such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR), protein content, sugar level and proline content. Besides, ZnONPs treatment enhanced secondary metabolites (phenols and flavonoids) contents and these metabolites potentially restricted excess H2O2 accumulation. In conclusion, our findings deciphered the potential functions of ZnONPs in alleviating Cd-induced phytotoxicity in pepper plants by boosting biomass production, photosynthesis, secondary metabolism and reducing oxidative stress.

Cortical Neurotransmitters Measured by Magnetic Resonance Spectroscopy Change Following Traumatic Brachial Plexus Injury.

Introduction GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the brain. In response to injury within the central nervous system, GABA promotes cortical plasticity and represents a potential pharmacological target to improve functional recovery. However, it is unclear how GABA changes in the brain after traumatic brachial plexus injuries (tBPIs) which represents the rationale for this pilot study. Methods We serially scanned seven males (mean age 42 years [SD 19] without head injury) up to 19 months after tBPIs. T1-weighted images (1-mm isotropic resolution) and J-edited spectra (MEscher-GArwood Point RESolved Spectroscopy [MEGA-PRESS], TE 68 ms, TR 2,000 ms, 2 cm isotropic voxels) were acquired using a MAGNETOM Prisma 3T (Siemens Healthcare, Erlangen, Germany). Data were analyzed in jMRUI blind to clinical information to quantify GABA, creatine plus phosphocreatine (Cr), and N-acetylaspartate (NAA) concentrations. Additionally, gray matter and white matter proportions were assessed using SPECTRIM software. Interhemispheric means were compared using linear methods. Confidence intervals (CIs) were generated to the 95% level. Results Within weeks of injury, the hemisphere representing the injured upper limb had a significantly lower GABA:NAA ratio (mean difference 0.23 [CI 0.06-0.40]) and GABA:Cr ratio (mean difference 0.75 [CI 0.24-1.25]) than the uninjured side. There were no interhemispheric differences in NAA:Cr. By 12 months post-injury, interhemispheric differences in metabolite concentrations equalized. There was no difference in the proportion of gray matter, white matter, or cerebrospinal fluid between the injured and uninjured hemispheres. Conclusion After brachial plexus injuries, there are interhemispheric differences in GABA concentrations within the sensory and motor cortex. This represents a potential pharmacological target that warrants further investigation.

Macromolecule Modelling for Improved Metabolite Quantification Using Short Echo Time Brain 1H-MRS at 3 T and 7 T: The PRaMM Model.

To improve reliability of metabolite quantification at both, 3 T and 7 T, we propose a novel parametrized macromolecules quantification model (PRaMM) for brain 1H MRS, in which the ratios of macromolecule peak intensities are used as soft constraints. Full- and metabolite-nulled spectra were acquired in three different brain regions with different ratios of grey and white matter from six healthy volunteers, at both 3 T and 7 T. Metabolite-nulled spectra were used to identify highly correlated macromolecular signal contributions and estimate the ratios of their intensities. These ratios were then used as soft constraints in the proposed PRaMM model for quantification of full spectra. The PRaMM model was validated by comparison with a single-component macromolecule model and a macromolecule subtraction technique. Moreover, the influence of the PRaMM model on the repeatability and reproducibility compared with those other methods was investigated. The developed PRaMM model performed better than the two other approaches in all three investigated brain regions. Several estimates of metabolite concentration and their Cramér-Rao lower bounds were affected by the PRaMM model reproducibility, and repeatability of the achieved concentrations were tested by evaluating the method on a second repeated acquisitions dataset. Although the observed effects on both metrics were not significant, the fit quality metrics were improved for the PRaMM method (p ≤ 0.0001). Minimally detectable changes are in the range 0.5-1.9 mM, and the percentage coefficients of variations are lower than 10% for almost all the clinically relevant metabolites. Furthermore, potential overparameterization was ruled out. Here, the PRaMM model, a method for an improved quantification of metabolites, was developed, and a method to investigate the role of the MM background and its individual components from a clinical perspective is proposed.

Plasma metabolomic signature of a proinflammatory diet in relation to breast cancer risk: a prospective cohort study.

A proinflammatory diet has been linked to an increased risk of breast cancer. However, the underlying metabolic roles remain to be elucidated. To investigate the metabolic mechanism between proinflammatory diet and breast cancer risk. This prospective study included 273,324 females from the UK Biobank. The dietary inflammatory potential was assessed via an energy-adjusted dietary inflammatory index (E-DII) based on a 24-hour recall questionnaire. The plasma metabolome was profiled via high-throughput nuclear magnetic resonance spectroscopy (NMR). A metabolic signature was constructed by summing selected metabolite concentrations weighted by the coefficients via absolute shrinkage and selection operator (LASSO) analysis. Multivariate Cox regression was applied to assess the associations of the E-DII and metabolic signature with breast cancer risk. We constructed a metabolic signature comprising 26 metabolites associated with a proinflammatory diet. These metabolites primarily included lipoproteins, amino acids, fatty acids, and ketone bodies. Both the E-DII and metabolic signature were positively associated with breast cancer risk (hazard ratio [HR] comparing the highest quintile to the lowest quintile = 1.17, 95% confidence interval [CI] = (1.04, 1.32); and 1.21, 95% CI = (1.01, 1.46), respectively). Furthermore, we found that saturated fatty acids to total fatty acids percentage and acetone concentration were positively associated (HR = 1.20, 95% CI = (1.04, 1.37); 1.15, 95% CI = (1.01, 1.32), respectively), while the degree of unsaturation was inversely associated with breast cancer risk (HR = 0.86; 95% CI = 0.75, 0.99). We identified a metabolic signature that reflects a proinflammatory diet and is associated with an increased risk of breast cancer.

Blood cortisol and faecal cortisol metabolite concentrations following an ACTH challenge in unanaesthetized brown bears (Ursus arctos).

Faecal cortisol metabolites (FCMs) are increasingly used to index physiological stress in wildlife. Cortisol and other stress hormones act to mobilize glucose, providing energy for the organism to respond to environmental perturbations. Cortisol, the predominant glucocorticoid (GC) in most mammals, is metabolized by the liver and excreted as FCMs. For FCMs to serve as a meaningful physiological index of stress in brown bears (Ursus arctos), we sought to quantify the relationship between blood cortisol and FCM concentrations. Consequently, we conducted an adrenocorticotropic hormone (ACTH) challenge on nine unanaesthetized captive brown bears at the Washington State University Bear Research, Education, and Conservation Center. We collected 10ml of blood at 0, 3, 6, 24, 48 and 72h post-injection to measure changes in blood cortisol concentrations. Faecal samples were collected between 7:00am and 8:00pm from 24h prior to injection through 72h post ACTH challenge. We found that FCM concentration was positively correlated with blood cortisol concentrations and that peak blood cortisol concentrations occurred between 3 and 6h following an ACTH challenge, whereas FCMs peaked between 10 and 27h after injection.

Metabolomics signatures of serotonin reuptake inhibitor (escitalopram), serotonin norepinephrine reuptake inhibitor (duloxetine) and cognitive-behavioral therapy on key neurotransmitter pathways in major depressive disorder.

Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this exploratory study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive-Behavioral Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways. Changes in metabolite concentrations related to each treatment arm were identified and compared to define metabolic signatures of exposure. In addition, association between metabolites and depressive symptom severity (assessed with the 17-item Hamilton Rating Scale for Depression [HRSD17]) and anxiety symptom severity (assessed with the 14-item Hamilton Rating Scale for Anxiety [HRSA14]) were evaluated, both at baseline and after 12 weeks of treatment. Significant reductions in serum serotonin level and increases in tryptophan-derived indoles that are gut bacterially derived were observed with escitalopram and duloxetine arms but not in CBT arm. These include indole-3-propionic acid (I3PA), indole-3-lactic acid (I3LA) and Indoxyl sulfate (IS), a uremic toxin. Purine-related metabolites were decreased across all arms. Different metabolites correlated with improved symptoms in the different treatment arms revealing potentially different mechanisms between response to antidepressant medications and to CBT.

Decreasing R:FR ratio in a grow light spectrum increases inflorescence yield but decreases plant specialized metabolite concentrations in Cannabis sativa

Decreasing R:FR ratio in a grow light spectrum increases inflorescence yield but decreases plant specialized metabolite concentrations in Cannabis sativa

Association Between Endocrine-Disrupting Chemicals Exposure and Attention-Deficit/Hyperactivity Disorder Symptoms in Children With Attention-Deficit/Hyperactivity Disorder.

This study investigated the relationship between exposure to endocrine-disrupting chemicals (EDCs), specifically phthalates, bisphenol A, bisphenol F, and bisphenol S, and the severity of attention-deficit/hyperactivity disorder (ADHD) symptoms using neuropsychological tests in children diagnosed with ADHD. This study included 67 medication-naïve children with ADHD aged 6-16 years. The urinary concentrations of EDCs were measured, and ADHD symptom severity was evaluated using neuropsychological tests and clinical symptom scale measurements. The Jonckheere-Terpstra test, Pearson and Spearman correlation analyses, linear regression models, and multiple regression models were used to examine the relationship between EDC exposure and ADHD symptoms. A significant correlation was observed between urinary phthalate metabolite concentrations and commission error T-scores in the visual Advanced Test of Attention test. No significant associations were found with other neuropsychological indicators or bisphenol levels. Phthalate exposure affects impulsivity in children with ADHD, which is consistent with the results of previous studies that used parental surveys. However, bisphenols are not clearly associated with ADHD symptoms, which is consistent with the results of previous studies.

Phytochemical Screening and Anti-hyperglycemic Effect Test of Ethanol Extract of Waru Leaf (Hibiscus tiliaceus) on Glucose-loaded Mice

Background: The treatment of diabetes mellitus relies on synthetic drugs with various side effects. Therefore, it is necessary to explore alternative treatments with herbal therapies, such as Hibiscus tiliaceus leaves. Objectives: The aim of this study was to determine the anti-hyperglycemic effect of an ethanol extract from Hibiscus tiliaceus leaves in glucose-loaded mice. Methods: The initial stage of dried leaf characterization was to ensure the identity, quality, purity, and safety to be used, and then extracted using the maceration method with 70% ethanol solvent. The next step was phytochemical screening to identify secondary metabolite content. The anti-hyperglycemic effect was evaluated using the oral glucose tolerance test (OGTT) on 25 male mice divided into five treatment groups. The negative control group was given Na CMC 0.5% w/v Na CMC, and the positive control group was administered glibenclamide. The ethanol extract of Hibiscus tiliaceus leaves was administered at doses of 200, 400, and 800 mg/kg. Approximately 200 µL of blood was collected and analyzed for glucose levels. The data were statistically analyzed using one-way analysis of variance (ANOVA) with SPSS ver. 25 program. Results: Hibiscus tiliaceus leaves contain alkaloids, flavonoids, saponins, and tannins. The highest decrease in blood glucose levels was observed in the ethanol extract group at a dose of 400 mg/kg BW, with a decrease of 78.52%, followed by a dose of 200 mg/kg BW of 76.63%, a dose group of 800 mg/kg BW of 73.48%, and a positive control group (glibenclamide) of 34.68%, which was significantly different from the negative control group (Na CMC 0.5%) (p < 0.05). Conclusion: The ethanol extract of H. tiliaceus has anti-hyperglycemic effects.

Evaluation of the antimicrobial activities of Napoleona imperialis leaf extracts against multi-drug resistant bacterial isolates from diabetic foot ulcer

Background: The increased resistance of Gram-negative bacteria, particularly those that produce extended beta-lactamase, are limiting the efficacy of antimicrobial drugs in treating infected diabetic foot ulcers. This study evaluates antimicrobial activities of Napoleona imperialis leaf extracts on bacterial isolates of diabetic foot ulcers as a way of developing novel antimicrobials that will be effective in treating infections caused by multi-drug-resistant (MDR) bacterial isolates. Methodology: Fresh leaves of N. imperialis were collected and identified by a plant taxonomist at the Department of Plant Biology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria. The leaves were washed and air- dried under shade and pulverized into fine powder using local milling machine. The pulverized plant was extracted using methanol, hexane, ethyl-acetate, and water. The test organisms used were MDR bacteria isolated from fresh clinical samples collected from patients with diabetic ulcer. The samples were processed using conventional cultures, biochemical identification and molecular detection by PCR methods, and antimicrobial susceptibility testing was done by the disc diffusion technique. The phytochemical compositions of the extract were assessed using standard methods. Antibacterial activity of the extracts was performed at a concentration of 400mg/ml of the extracts using agar well diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MIC) of the extracts were determined using serial (doubling) dilution technique. The time-kill assay of the plant extract was also evaluated. Results: The MDR isolates recovered from the diabetic ulcer were Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. The plant extract yield showed that aqueous fraction of the leaf extract gave higher yield of 37.3%, followed by ethyl acetate fraction of the leaf extract at 26.8%, hexane fraction of the leaf extract at 22.3%, and the least was crude methanol leaf extract at 13.4%. The phytochemical analysis showed that the leaf extracts contained phenols, flavonoid, tannins, glycosides, alkaloids, saponin, terpenoids and triterpenes. The methanol extract produced highest mean inhibition zone diameter of 19.7±00mm against E. coli, 19.3±1.2mm against P. aeruginosa, 19.3±1.2mm against S. pneumoniae, 18.7±1.2mm against S. aureus and 17.7±1.5mm against K. pneumoniae. The bacteriostatic (MIC) activities of this methanol extract at different concentrations ranged from 3.125 to 25.00mg/ml, and bactericidal (MBC) activities ranged from 6.25 to 50.00mg/ml. The time- kill assay of the crude methanol leaf extract at 1xMIC, 2xMIC and 3x MIC showed a decrease in the number of viable cells count of the initial inoculum within 2-8 hours of incubation, indicating high activity. Conclusion: The methanol leaf extracts of N. imperialis could be used as a complementary source of antimicrobials to the conventional antibiotic in the treatment of wound infections caused by MDR bacteria due to the contents of essential secondary metabolites in the plant extract and the antibacterial activities observed.

In vitro assessment of Bionectria ochroleuca metabolites: A promising approach for controlling root-knot nematode, Meloidogyne incognita

Meloidogyne incognita, a highly destructive root-knot nematode, causes substantial crop losses worldwide by infesting plant roots, which disrupts nutrient and water uptake. This pest is notoriously challenging to manage due to its broad host range and growing resistance to many chemical nematicides, emphasizing the urgent need for sustainable, eco-friendly alternatives. In this context, the current study investigated the nematicidal potential of secondary metabolites derived from the entomopathogenic fungus, Bionectria ochroleuca against M. incognita. The in vitro assays demonstrated a dose- and time-dependent inhibition of egg hatching and juvenile survival. At a crude metabolite concentration of 100%, egg hatching was reduced to 5.64% and juvenile mortality increased to 95.4% after 72 h. Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified key metabolites, including palmitic acid, butanedioic acid, lactic acid, and oleic acid, which appear to inhibit nematode growth through mechanisms that impair cell membrane integrity, disrupt energy metabolism, and interfere with essential metabolic pathways. Further, metabolite enrichment analysis revealed their involvement in the biosynthetic pathways, such as unsaturated fatty acids, galactose metabolism, and phenylalanine metabolism. Molecular docking studies supported these findings by showing high binding affinities of these metabolites to virulent nematode proteins, including Cytochrome c oxidase subunit 1 and NAD(H) oxidase, suggesting interference with essential biological processes within the nematode. Overall, these findings position the metabolites of B. ochroleuca as promising candidates for managing nematode infestations, offering a potent alternative to chemical nematicides and thereby contributing to sustainable agricultural practices.

Indole derivatives and their associated microbial genera are associated with the 1-year changes in cardiometabolic risk markers in Chinese adults

BackgroundAlthough emerging evidence suggests that indole derivatives, microbial metabolites of tryptophan, may improve cardiometabolic health, the effective metabolites remain unclear. Also, the gut microbiota that involved in producing indole derivatives are less studied. We identified microbial taxa that can predict serum concentrations of the key indole metabolite indole-3-propionic acid (IPA) at population level and investigated the associations of indole derivatives and IPA-predicting microbial genera with cardiometabolic risk markers.MethodsIn a cohort of 318 community-dwelling adults, serum indole metabolites and fecal microbiota (16S ribosomal RNA) were measured at baseline. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose were repeatedly measured at baseline and again after 1 year. Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were measured after 1 year. The association between indole derivatives and the 1-year changes in blood lipids and glucose, and association of indole derivatives with baPWV and ABI were investigated using linear regression models.ResultsEach 1 µmol/L increase in indole-3-acetic acid (IAA) levels was associated with 5.08% (P = 0.046) decrease in LDL-C. IPA levels were inversely associated with baPWV (percentage difference = -1.32%, P = 0.036). Per 1 µmol/L increase in Indole-3-aldehyde (IAld) levels was associated with 1.91% (P = 0.004) decrease in TC and 0.58% (P = 0.019) increase in ABI, but 1.79% decrease in HDL-C with borderline significance (P = 0.050). We identified 18 bacterial genera whose relative abundance was positively associated with serum IPA concentrations (PFDR < 0.05) and constructed a microbial score to reflect the overall IPA-producing potential. This score was inversely associated with baPWV (percentage difference = -0.48%, P = 0.007).ConclusionsOur results suggest that IAA, IPA, IAld, and IPA-predicting microbial score are favorably associated with several cardiometabolic risk markers, although IAld may decrease HDL-C levels.

Associations between fecal glucocorticoid levels and social bonds vary with relatedness in juvenile rhesus macaques

Strong social bonds in gregarious adult animals have been associated with lower levels of glucocorticoids. However, similar research is lacking for juvenile primates. We examined relationships between social bonds and mean concentrations of fecal glucocorticoid metabolites (fGCMs) in 44 free-ranging juvenile rhesus macaques (Macaca mulatta) on Cayo Santiago, Puerto Rico. We measured frequencies of affiliative behavior (grooming, play, approaches and proximity) with other same-sex, same-aged juveniles (peers) and the total number of affiliative peer relationships. We found a positive relationship between fGCMs and grooming frequencies. Females that spent more time in proximity to peers also had higher fGCMs. In contrast, among juveniles with more closely related peers, those with more affiliative peers or more frequent play bouts had lower fGCMs. However, strong peer bonds in most juveniles did not appear to be associated with reduced glucocorticoid levels. fGCMs were higher for females than males, but were unassociated with physical activity, aggression, or peer seeking tendencies. We propose that the establishment and navigation of some peer bonds at this life stage may involve increased metabolic demand.