Metabolite Concentrations Research Articles

Hybridization promotes growth performance by altering rumen microbiota and metabolites in sheep.

Hybridization can substantially improve growth performance. This study used metagenomics and metabolome sequencing to examine whether the rumen microbiota and its metabolites contributed to this phenomenon. We selected 48 approximately 3 month-old male ♂Hu × ♀Hu (HH, n = 16), ♂Poll Dorset × ♀Hu (DH, n = 16), and ♂Southdown × ♀Hu (SH, n = 16) lambs having similar body weight. The sheep were fed individually under the same nutritional and management conditions for 95 days. After completion of the trial, seven sheep close to the average weight per group were slaughtered to collect rumen tissue and content samples to measure rumen epithelial parameters, fermentation patterns, microbiota, and metabolite profiles. The final body weight (FBW), average daily gain (ADG), and dry matter intake (DMI) values in the DH and SH groups were significantly higher and the feed-to-gain ratio (F/G) significantly lower than the value in the HH group; additionally, the papilla height in the DH group was higher than that in the HH group. Acetate, propionate, and total volatile fatty acid (VFA) concentrations in the DH group were higher than those in the HH group, whereas NH3-N concentration decreased in the DH and SH groups. Metagenomic analysis revealed that several Prevotella and Fibrobacter species were significantly more abundant in the DH group, contributing to an increased ability to degrade dietary cellulose and enrich their functions in enzymes involved in carbohydrate breakdown. Bacteroidaceae bacterium was higher in the SH group, indicating a greater ability to digest dietary fiber. Metabolomic analysis revealed that the concentrations of rumen metabolites (mainly lysophosphatidylethanolamines [LPEs]) were higher in the DH group, and microbiome-related metabolite analysis indicated that Treponema bryantii and Fibrobacter succinogenes were positively correlated with the LPEs. Moreover, we found methionine sulfoxide and N-methyl-4-aminobutyric acid were characteristic metabolites in the DH and SH groups, respectively, and are related to oxidative stress, indicating that the environmental adaptability of crossbred sheep needs to be further improved. These findings substantially deepen the general understanding of how hybridization promotes growth performance from the perspective of rumen microbiota, this is vital for the cultivation of new species and the formulation of precision nutrition strategies for sheep.

Metabolit Sekunder dan Aktivitas Antibakteri Ekstrak Metanol Daun Kamboja Putih (Plumeria acuminata Ait) Terhadap Beberapa Bakteri Uji

Kamboja (Plumeria acuminata Ait) plant is traditional medicine used as medication for ulcer and abscess. Steroid and tanin is component of chemical compound in kamboja leaves that supposed to have antibacterial activity. This study aims to determine the content of secondary metabolites and effective concentration of methanol extracts of kamboja leaves as antibacterial. Identification contains of secondary metabolites by used reagent Mayer, Dragendorf, Liebermann-Burchard, FeCl, Mg powder and HCl. Analysis of secondary metabolites characterized by the presence of sediment or froth. The antibacterial activity test carried out by agar diffusion method. Inhibition zone is analyzed by Anava and Duncan test. Secondary metabolite the compound containing steroid and tanin. The effective concentration of 40% were significantly different with a value of p = 0.00 (p<0.05) on the growth of Streptococcus mutans and Staphylococcus aureus bacteria and a concentration of 30% is very significantly different from the value of p = 0.00 (p<0.05) on the growth of Escherichia coli bacteria in vitro.

Association between phthalates exposure and non-alcoholic fatty liver disease under different diagnostic criteria: a cross-sectional study based on NHANES 2017 to 2018.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. Phthalates have been suggested to influence the development of NAFLD due to their endocrine-disrupting properties, but studies based on nationally representative populations are insufficient, and existing studies seem to have reached conflicting conclusions. Due to changes in legislation, the use of traditional phthalates has gradually decreased, and the phthalates substitutes is getting more attention. This study aims to delve deeper into how the choice of diagnostic approach influences observed correlations and concern about more alternatives of phthalates, thereby offering more precise references for the prevention and treatment of NAFLD. A cohort of 641 participants, sourced from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 database, was evaluated for NAFLD using three diagnostic methods: the Hepatic Steatosis Index (HSI), the US Fatty Liver Indicator (US.FLI), and Vibration Controlled Transient Elastography (VCTE). The urinary metabolite concentrations of Di-2-ethylhexyl phthalate (DEHP), Di-isodecyl phthalate (DIDP), Di-isononyl phthalate (DINP), Di-n-butyl phthalate (DnBP), Di-isobutyl phthalate (DIBP), Di-ethyl phthalate (DEP) and Di-n-octyl phthalate (DnOP) were detected. The association between NAFLD and urinary phthalate metabolites was evaluated through univariate and multivariate logistic regression analyses, considering different concentration gradients of urinary phthalates. Univariate logistic regression analysis found significant correlations between NAFLD and specific urinary phthalate metabolites, such as Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and Mono-(carboxyisoctyl) phthalate (MCiOP), across different diagnostic criteria. In a multivariate logistic regression analysis adjusting only for demographic data, MEOHP (OR = 3.26, 95% CI = 1.19-8.94, p = 0.029), MEHHP (OR = 3.98, 95% CI = 1.43-11.1, p = 0.016), MECPP (OR = 3.52, 95% CI = 1.01-12.2, p = 0.049), and MCiOP (OR = 4.55, 95% CI = 1.93-10.7, p = 0.005) were positively related to NAFLD defined by HSI and VCTE. The correlation strength varied with the concentration of phthalates, indicating a potential dose-response relationship. Adjusting for all covariates in multivariate logistic regression, only MCiOP (OR = 4.22, 95% CI = 1.10-16.2, p = 0.044), as an oxidative metabolite of DINP, remained significantly associated with NAFLD under the VCTE criterion, suggesting its potential role as a risk factor for NAFLD. This research highlights a significant association between DINP and NAFLD. These findings underscore the need for further investigation into the role of the phthalates substitutes in the pathogenesis of NAFLD and the importance of considering different diagnostic criteria in research.

Biological characteristics of marine Streptomyces SK3 and optimization of cultivation conditions for production of compounds against Vibiriosis pathogen isolated from cultured white shrimp (Litopenaeus vannamei).

Antibiotic resistance in shrimp farms has emerged as an extremely serious situation worldwide. The main aim of this study was to optimize the cultural conditions for producing new antibiotic agents from marine Streptomyces species. Streptomyces SK3 was isolated from marine sediment and was identified by its 16S rDNA as well as biochemical characteristics. This microbe produced the highest concentration of bioactive secondary metabolites (BSMs) when cultured in YM medium (YM/2). It produced the maximum total protein (41.8 ± 6.36 mg/ml) during the late lag phase period. The optimum incubation temperature was recorded at 30 °C; BSMs were not produced at ≤10 °C within an incubation period of 3-4 days. The suitable agitation speed was found to be 200 rpm with pH 7.00. The proper carbon, nitrogen, and trace elements supplementation consisted of starch, malt extract, calcium carbonate (CaCO3), and magnesium sulfate (MgSO4). The ethyl acetate extract was found to act strongly against three vibriosis pathogens, Vibrio harveyi, Vibrio parahaemolyticus, and Vibrio vunificus, as indicated by the inhibition zones at 34.5, 35.4, and 34.3 mm, respectively. The extract showed the strongest anti-V. harveyi activity, as indicated by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.101 ± 0.02 and 0.610 ± 0.04 mg/ml, respectively. Basic chemical investigation of the crude extract using thin layer chromatography (TLC), bioautography, liquid chromatography tandem mass spectrometry (LC‒MS/MS), Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance (1H-NMR) revealed that the active components were the terpenoid and steroid groups of compounds. They showed carboxylic acid and ester functions in their molecules.

The Effectiveness of Tawandakulo (Kleinhovia Hospita L.) On SGOT, SGPT Enzyme Levels, and Hepatocyte Regeneration in Paracetamol-Induced Rats

Background:Paracetamol is metabolized by cytochrome P450 enzymes into a highly toxic reactive metabolite, N-acetyl-p-benzoquinonimine (NAPQI), which can cause liver damage. Antioxidants play a crucial role in mitigating liver toxicity. Kleinhovia hospitaL. (also known as Tawandakulo) is a potent plant antioxidant due to its content of secondary metabolites, such as phenolics, flavonoids, saponins, and terpenoids. Objective:This study aimed to investigate the levels of SGOT and SGPT enzymes, as well as liver histopathology, as indicators of liver health. Methods:An experimental research design with a randomized post-test control group was used. The study involved 25 rats, randomly divided into five groups. Paracetamol was administered at a toxic dose of 2.5 g/kg body weight, dissolved in distilled water, and given orally through NGT no. 5. Results:The study found a decrease in SGOT levels in the treatment group and a significant reduction in SGPT enzyme levels between pre-intervention (P2) and post-intervention (P3). There was a significant change in enzyme levels in treatment group 2 (p = 0.00) and treatment group 3 (p = 0.03). However, no significant difference was observed in treatment group 4 (p = 0.09). Liver cells in treatment groups P1, P2, and P3 showed signs of regeneration, whereas cells in the control group did not regenerate. Group P4 exhibited slower liver cell regeneration than the other treatment groups. Conclusion:This study concludes that a decoction of Kleinhovia hospitaL. can stimulate liver cell growth and reduce SGOT and SGPT enzyme levels. Keywords: Kleinhovia hospitaL; SGOT; SGPT; Liver cell regeneration; Indonesia.

Metabolomic Fingerprints of Medical Therapy Versus Bariatric Surgery in Patients With Obesity and Type 2 Diabetes: The STAMPEDE Trial.

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective procedures to treat and manage type 2 diabetes (T2D). However, the underlying metabolic adaptations that mediate improvements in glucose homeostasis remain largely elusive. The purpose of this study was to identify metabolic signatures associated with biochemical resolution of T2D after medical therapy (MT) or bariatric surgery. Plasma samples from 90 patients (age 49.9 ± 7.6 years; 57.7% female) randomly assigned to MT (n = 30), RYGB (n = 30), or SG (n = 30) were retrospectively subjected to untargeted metabolomic analysis using ultra performance liquid chromatography with tandem mass spectrometry at baseline and 24 months of treatment. Phenotypic importance was determined by supervised machine learning. Associations between change in glucose homeostasis and circulating metabolites were assessed using a linear mixed effects model. The circulating metabolome was dramatically remodeled after SG and RYGB, with largely overlapping signatures after MT. Compared with MT, SG and RYGB profoundly enhanced the concentration of metabolites associated with lipid and amino acid signaling, while limiting xenobiotic metabolites, a function of decreased medication use. Random forest analysis revealed 2-hydroxydecanoate as having selective importance to RYGB and as the most distinguishing feature between MT, SG, and RYGB. To this end, change in 2-hydroxydecanoate correlated with reductions in fasting glucose after RYGB but not SG or MT. We identified a novel metabolomic fingerprint characterizing the longer-term adaptations to MT, RYGB, and SG. Notably, the metabolomic profiles of RYGB and SG procedures were distinct, indicating equivalent weight loss may be achieved by divergent effects on metabolism.

High light intensity improves yield of specialized metabolites in medicinal cannabis (Cannabis sativa L.), resulting from both higher inflorescence mass and concentrations of metabolites

Medicinal cannabis (Cannabis sativa L.) contains various plant specialized metabolites, such as cannabinoids and terpenoids. These metabolites are mainly accumulated in inflorescences and are the primary focus of cultivation. Medicinal cannabis is often cultivated in indoor farming with electrical light, which allows for light intensities to optimize quantity and quality of production. Although it is known that an increase in light intensity results in increased inflorescence yield in cannabis, its impact on specialized metabolites remains unclear. We aim to quantify the effects of light intensity on the yield of specialized metabolites, and to elucidate which plant traits explain these effects, using a yield component analysis. Hereto, we conducted an experiment in a climate-controlled chamber using broad-band white LEDs at three light intensities: 600, 800, and 1000 µmol m−2 s−1 photosynthetic photon flux density (PPFD), applied during the generative phase (8 weeks with a 12-h photoperiod) in cannabis cv. ‘Critical CBD’. Yield of specialized metabolites, including cannabinoids and terpenoids, strongly increased with increasing PPFD due to increases in both their concentrations and inflorescence yield. The inflorescence yield showed a proportional increase with PPFD, resulting in a constant light use efficiency. The higher inflorescence dry mass was mainly caused by an increase in total plant dry matter production, and to a lesser extent a larger fraction of dry mass partitioned to the inflorescences. Leaf photosynthesis was higher for plants grown at higher PPFD. This study shows that cannabis can use very high light intensity, resulting in high yield of specialized metabolites due to high inflorescence mass and metabolite concentrations.

El extracto metanólico de <i>Tillandsia recurvata</i> reduce los niveles de glucosa, triglicéridos y colesterol en sangre

Background: Tillandsia recurvata collected in San Luis Potosí does not have studies focused on its use as an adjuvant in treating diabetes mellitus. Questions and / or Hypotheses: Will Tillandsia recurvata L. (Bromeliaceae) have antidiabetic activity in vitro and in vivo? Studied species: Tillandsia recurvata L. (Bromeliaceae) Study site and dates: T. recurvata was collected in Guadalcázar municipality, San Luis Potosí, México, in December 2021. Methods: The antidiabetic potential of Tillandsia recurvata methanol extract (TRM) was evaluated using in vitro and in vivo models, and its secondary metabolite content was analyzed using Gas chromatography-mass spectrometry. Results: Results demonstrate that extract reduces blood glucose, triglyceride, and cholesterol levels in vivo. In addition, in vitro tests showed that extract diminished the formation of advanced glycation end products, methylglyoxal concentrations, and glycosylated hemoglobin levels. Gas chromatography-mass spectrometry analysis identified several compounds in the extract, including 2-methylbenzaldehyde, 4-hydroxy-2-methylacetophenone, 3',5' dimethoxyacetophenone, pentanoic acid, palmitic acid, linoleic acid, phytol, margaric acid, oleamide, cis-11-eicosenamide, stearic acid, 13-docosenamide, (Z), campesterol, and β-sitosterol. Conclusions: These results highlight the potential of T. recurvata collected in San Luis Potosi as an adjuvant in treatment of diabetes mellitus.

Wearable SERS sensor based on Bionic Sea urchin-Cavity structure for dual in-situ detection of metabolites and VOCs gas

Diagnosis of diseases by monitoring the metabolite concentration on the skin surface and volatile organic compounds (VOCs) in exhaled gas is an active area of research with great potential for development and application. Therefore, the development of a sensor that can monitor in real time slight changes in metabolite concentrations on the surface of the skin in the resting state and accurately detect VOCs gases in exhaled gas is of significant practical value. To address these challenges, we designed and fabricated the wearable Bionic Sea urchin-Cavity (BSC) SERS sensor with high sensitivity and adaptability. Our testing revealed that the SERS sensor exhibited strong responsiveness to human metabolites. The subtle concentration changes in urea on the resting state skin surface also successfully detected. Furthermore, the SERS sensor successfully detected trace acetone gas volatilized from the 30 mmol/L aqueous acetone solution similar to the acetone concentration in diabetic blood. We anticipate that this SERS sensor could serve as a multi-functional wearable device for medical applications and provide a new platform for the field.

Nutritional Qualities, Metabolite Contents, and Antioxidant Capacities of Yardlong Beans (Vigna unguiculata subsp. sesquipedalis) of Different Pod and Seed Colors.

Studying the effects of genetic and environmental factors on plant biochemical components helps in selecting the best varieties for the food industry and breeding programs. This study analyzed the nutritional qualities, secondary metabolites, and antioxidant activities of 14 field-grown yardlong beans accessions and how they are affected by differences in pod and seed colors. The analyzed parameters varied significantly among the yardlong bean accessions, with variances ranging from 1.36% in total unsaturated fatty acid content to 51.01% in DPPH• scavenging activity. Accessions YLB4, YLB7, and YLB14 performed the best, showing antioxidant indices of 100.00, 70.10, and 67.88%, respectively. Among these, YLB14 showed a characteristic property, having the highest levels of vitamin C (2.62 mg/g) and omega-6 to omega-3 ratio (2.67). It also had the second highest dietary fiber (21.45%), stearic acid (4.44%), and linoleic acid (40.39%) contents, as well as the lowest thrombogenicity index (0.38). Although cluster and principal component analyses did not clearly separate the yardlong beans based on pod or seed color, analysis of variance revealed that these factors and their interaction had significant effects on total phenol, DPPH• scavenging activity, ABTS•+ scavenging activity, and reducing power. In contrast, the nutritional parameters, except for dietary fiber, were not significantly affected by pod and seed color variations. Therefore, consuming yardlong beans of different pod and seed colors may not affect the overall nutrient intake. In general, this study identified yardlong beans with green pods and black seeds as good sources of antioxidants. Accordingly, further metabolomics and genomics studies are suggested to thoroughly explore their characteristics.

Rifaximin ameliorates influenza A virus infection-induced lung barrier damage by regulating gut microbiota

Prior research has indicated that the gut-lung-axis can be influenced by the intestinal microbiota, thereby impacting lung immunity. Rifaximin is a broad-spectrum antibacterial drug that can maintain the homeostasis of intestinal microflora. In this study, we established an influenza A virus (IAV)-infected mice model with or without rifaximin supplementation to investigate whether rifaximin could ameliorate lung injury induced by IAV and explore the molecular mechanism involved. Our results showed that IAV caused significant weight loss and disrupted the structure of the lung and intestine. The analysis results of 16S rRNA and metabolomics indicated a notable reduction in the levels of probiotics Lachnoclostridium, Ruminococcaceae_UCG-013, and tryptophan metabolites in the fecal samples of mice infected with IAV. In contrast, supplementation with 50 mg/kg rifaximin reversed these changes, including promoting the repair of the lung barrier and increasing the abundance of Muribaculum, Papillibacter and tryptophan-related metabolites content in the feces. Additionally, rifaximin treatment increased ILC3 cell numbers, IL-22 level, and the expression of RORγ and STAT-3 protein in the lung. Furthermore, our findings demonstrated that the administration of rifaximin can mitigate damage to the intestinal barrier while enhancing the expression of AHR, IDO-1, and tight junction proteins in the small intestine. Overall, our results provided that rifaximin alleviated the imbalance in gut microbiota homeostasis induced by IAV infection and promoted the production of tryptophan-related metabolites. Tryptophan functions as a signal to facilitate the activation and movement of ILC3 cells from the intestine to the lung through the AHR/STAT3/IL-22 pathway, thereby aiding in the restoration of the barrier.Key points• Rifaximin ameliorated IAV infection-caused lung barrier injury and induced ILC3 cell activation.• Rifaximin alleviated IAV-induced gut dysbiosis and recovered tryptophan metabolism.• Tryptophan mediates rifaximin-induced ILC3 cell activation via the AHR/STAT3/IL-22 pathway.

Interactions between invasive pests and pathogens in a native chestnut forest

The introduction in the same area of different invasive species can result in novel interactions, with unpredictable consequences. We carried out a study in Galicia (northwestern Iberian Peninsula) with the aim of clarifying the interactions between two invasive species Cryphonectria parasitica and Dryocosmus kuriphilus. In 2018, we selected five chestnut plots affected by both species. We compared trees affected only by the insect and trees affected by both the insect and the fungus with respect to attack level, gall characteristics, female size and fecundity, and concentrations of nitrogen, water and secondary metabolites. We also evaluated female preferences in a greenhouse assay. There were higher levels of attack in trees affected by both invaders. However, the greenhouse assay showed that ovipositing females do not preferentially choose trees attacked by the fungus. The presence of the fungus had no effect on the size, wall thickness, or hardness of D. kuriphilus galls, but larvae were smaller in trees also affected by the fungus. The fecundity of females was strongly related to the presence of chestnut blight; the number of eggs per female was almost double in trees affected by the fungus. There were no relations between blight and the nitrogen or water content in the galls, where the insects feed. There were also no effects of chestnut blight on the concentration of terpenes or phenols, but condensed tannins were higher in trees with chestnut blight. The higher tannins induced by chestnut blight may directly or indirectly benefit gall wasps. Positive relationships between condensed tannin concentration and reproductive performance of other gall makers were previously reported. Tannins can also improve the negative effects of environmental conditions inside the gall. Our results indicate that the presence of chestnut blight can increase the suitability of chestnut trees for the invasive insect, D. kuriphilus, through the increase in tannins due to the presence of the fungus.

Phthalate exposure as a hidden risk factor for uterine leiomyoma in adult women: Accumulated evidence from observational studies

BackgroundThere is evidence that exposure to phthalate in women may increase the risk of uterine leiomyomas. Whereas, the association between exposure to phthalate and the incidence of uterine leiomyoma remained inconclusive. MethodsA meta-analysis was performed to evaluate their relationship. Literature eligible for inclusion was found in PubMed, EMBASE, Web of Science, and WanFang Medical Database. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to assess the risk for effect estimate for each phthalate. ResultsA total of fourteen observational studies with 5777 subjects of adult women were included in this study. In the pooled analysis, we found an elevated risk of uterine leiomyoma among women who were exposed to higher levels of di-2-ethylhexyl phthalate (DEHP) (OR 1.61, 95 % CI: 1.18–2.20), as estimated indirectly from the molar summation of its urinary metabolite concentrations. In addition, a positive association was observed between the occurrence of uterine leiomyoma and exposure to low molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.00–1.15), as well as high molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.01–1.15), as quantified by integrating the effect estimates of individual metabolite from each study. Urinary levels of DEHP metabolites, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, monoethyl phthalate, and monomethyl phthalate were not appreciably correlated with the risk of uterine leiomyoma. ConclusionOur results indicated that exposure to DEHP, and co-exposure to high or low molecular weight phthalate mixture might be potential risk factors for uterine leiomyoma in adult women. Owing to the indirect estimation of association, when interpreting these findings, cautions should be taken.

Pharmacokinetics and thermal anti-nociceptive effects of oral morphine in horses.

Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed. Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration. Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses.

3-epi-18β-glycyrrhetinic acid or its glucuronide, the metabolites of glycyrrhizinic acid with individual differences, correlated with diagnostic maker for licorice-induced pseudoaldosteronism in humans.

Licorice is a crude drug that is used in traditional Japanese Kampo medicine and is also used as a sweetener. Occasionally, it causes pseudoaldosteronism (PsA) as a side effect. The major symptoms include hypokalemia, hypertension, edema, and low plasma aldosterone levels. PsA might be caused by the metabolites of glycyrrhizinic acid (GL), a component of licorice. The development of PsA markedly varies among individuals; however, the factors that cause these individual differences remain unknown. In this study, 78 patients who consumed Kampo medicines containing licorice were enrolled, and their laboratory data, including serum potassium levels, plasma aldosterone concentrations (PAC), and the concentrations of GL metabolites in the residual blood and/or urine samples were evaluated. Of the 78 participants, 18β-glycyrrhetinic acid (GA), 3-epi-GA, 3-oxo-GA, 18β-glycyrrhetinyl-30-O-glucuronide (GA30G), and 3-epi-GA30G were detected in the serum samples of 65, 47, 63, 62, and 3 participants, respectively. Of the 29 urine samples collected, GA30G and 3-epi-GA30G were detected in 27 and 19 samples. 3-epi-GA30G is a newly found GL metabolite. Moreover, 3-epi-GA, 3-oxo-GA, and 3-epi-GA30G were identified in human samples for the first time. High individual differences were found in the appearances of 3-epi-GA in serum and 3-epi-GA30G in urine, and the concentrations of these metabolites were correlated with serum PsA markers. The inhibitory titers of 3-epi-GA, 3-oxo-GA, GA30G, and 3-epi-GA30G on human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) were almost similar. These findings suggest that 3-epi-GA and/or 3-epi-GA30G are associated with individual differences in the development of PsA. Significance Statement In this study, we detected 3-epi-GA in human serum for the first time. We also identified 3-epi-GA30G as a novel GL metabolite in human urine. These GL metabolite levels showed correlations with markers of PsA. Additionally, there are individual differences in whether or not they appear in the serum/urine. In conclusion, 3-epi-GA/3-epi-GA30G correlates with individual differences in the development of PsA.

Longitudinal study and predictive modelling of urinary pesticide metabolite concentrations in residents of Guangzhou, China

Continuous human biomonitoring and predictive modelling of urinary pesticide metabolites are critical for evaluating pesticide exposure trends and associated health risks. We conducted repeat cross-sectional surveys to determine the urinary concentrations of eight pesticide metabolites in the residents of Guangzhou, China, from 2018 to 2022. We longitudinally analyzed the changes in these metabolite concentrations over the years and assessed the potential non-carcinogenic risks by calculating the hazard quotient and hazard index. No significant differences were observed in the total urinary pesticide metabolite concentrations over the 5 years (9.16–12.99 μg/L). The urinary concentrations of 3,5,6-trichloro-2-pyridinol and 2,4-dichlorophenoxyacetic acid reached their lowest levels in 2020 (1.47 and 0.11 μg/L). Conversely, urinary para-nitrophenol concentrations exhibited an inverse trend, peaking in 2020 (6.16 μg/L). The composition profiles of urinary pesticide metabolites showed that para-nitrophenol consistently constituted the largest proportion each year. Males consistently showed higher median concentrations of total urinary pesticide metabolites and individual metabolites of 3,5,6-trichloro-2-pyridinol, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid, and para-nitrophenol than females. The concentrations of cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid in adults' urine were significantly higher than those in minors' urine each year. The total pesticide metabolite concentrations in adults' urine were significantly higher than those in minors' urine in 2018 and 2020, whereas no significant differences were observed in other years. No significant differences in urinary pesticide metabolite concentrations were observed among different BMI groups. Results showed that 14.17% of the population had hazard index values above 1, indicating a higher risk of health hazards. Three predictive models were employed to predict urinary pesticide metabolite concentrations for 2023–2024, revealing an increasing trend in 3,5,6-trichloro-2-pyridinol concentrations while other metabolites are expected to decrease. The study showed the concentration of para-nitrophenol peaked in 2020 while 3,5,6-trichloro-2-pyridinol and 2,4-dichlorophenoxyacetic acid reached their lowest levels, suggests that the COVID-19 pandemic may have influenced pesticide exposure patterns.

Chitosan and its derivatives regulate lactic acid synthesis during milk fermentation.

The influence of chitosan's physicochemical characteristics on the functionality of lactic acid bacteria and the production of lactic acid remains very obscure and contradictory to date. While some studies have shown a stimulatory effect of oligochitosans on the growth of Lactobacillus spp, other studies declare a bactericidal effect of chitosan. The lack and contradiction of knowledge prompted us to study the effect of chitosan on the growth and productivity of L. bulgaricus in the presence of chitosan and its derivatives. We used high molecular weight chitosan (350 kDa) and oligochitosans (25.4 and 45.3 kDa). The experiment was carried out with commercial strain of L. bulgaricus and the low fat skim cow milk powder reconstituted with sterile distilled water. After fermentation, dynamic viscosity, titratable acidity, pH, content of lactic acid, colony forming units, chitosan and oligochitosans radii were measured in the samples. Fermented dairy products were also examined using sodium dodecyl sulfate electrophoretic analysis, gas chromatography-mass spectrometry and light microscopy. The results of the study showed that when L. bulgaricus was cultured in the presence of 25.4 kDa oligochitosans at concentrations of 0.0025%, 0.005%, 0.0075% and 0.01%, the average rate of LA synthesis over 24 hours was 11.0 × 10-3 mol/L/h, 8.7 × 10-3 mol/L/h, 6.8 × 10-3 mol/L/h, 5.8 × 10-3 mol/L/h, respectively. The 45.3 kDa oligochitosans had a similar effect, while the average rate of lactic acid synthesis in the control sample was only 3.5 × 10-3 mol/L/h. Notably, 350 kDa chitosan did not affect the rate of lactic acid synthesis compared with the control sample. Interestingly, interaction of chitosan with L. bulgaricus led to a slowdown in the synthesis of propanol, an increase in the content of unsaturated and saturated fatty acids, and a change in the composition and content of other secondary metabolites. The quantity of L. bulgaricus in a sample with 0.01% chitosan exceeded their content in the control sample by more than 1,700 times. At the same chitosan concentration, the fermentation process was slowed down, increasing the shelf life of the fermented milk product from 5 to 17 days while maintaining a high content of L. bulgaricus (6.34 × 106 CFU/g).

Crotalaria quinquefolia L. Revealed as a Potential Source of Neuropharmacophore in Both Experimental and Computational Studies.

Herbal remedies have shown great promise for improving human health. The plant Crotalaria quinquefolia is used in folk medicine to cure different diseases, including scabies, fever, discomfort, and lung infections. The present research was designed to explore bioactive compounds and evaluate the neuropharmacological effects of C. quinquefolia through in vivo and in silico approaches. Different secondary metabolites as well as the antioxidant activity were measured. Furthermore, chemical compounds were identified by HPLC and GCMS analysis. The neuropharmacological activity was examined by hole cross, hole board, open field, Y-maze, elevated plus maze, and thiopental sodium induced sleeping time tests in mice at doses of 100 mg/kg and 200 mg/kg body weight. Besides, an in-silico study was performed on proteins related to Alzheimer disease. The extract showed a significant content of secondary metabolites and antioxidant potential. The in-silico analysis showed that myricetin, quercetin, rutin, and kaempferol have good binding affinity with studied proteins, and QSAR studies revealed potential benefits for treating dementia, age-related macular degeneration, and more. The findings of the present neurological activity collectively imply that the extract has strong CNS depressant and anxiolytic activity. Therefore, C. quinquefolia can be a potential source of secondary metabolites to treat Alzheimer disease.

Active-matrix extended-gate field-effect transistor array for simultaneous detection of multiple metabolites

With the deepening understanding of diseases, increasing attention has been paid to personalized healthcare and precise diagnosis, which usually depend on the simultaneous monitoring of multiple metabolites, therefore requiring biological sensing systems to possess high sensitivity, specificity, throughput, and instant monitoring capabilities. In this work, we demonstrated the active-matrix extended-gate field-effect transistor (AMEGFET) array that can perform instant analysis of various metabolites in small amounts of body fluids collected during routine physiological activities. The extended gate electrodes of the AMEGFETs comprise ordered mesoporous carbon fibers loaded with both oxidoreductase enzymes for specific metabolites and platinum nanoparticles. By selecting customized electrode combinations, the AMEGFET array can monitor the concentrations of metabolites closely associated with chronic diseases and lifestyles, such as glucose, uric acid, cholesterol, ethanol, and lactate. The switch function of AMEGFET not only simplifies the readout circuitry for large-scale arrays but also avoids the mutual interferences among sensing units. The high flexibility and scalability make the AMEGFET array widely applicable in establishing high-throughput sensing platforms for biomarkers, providing highly efficient technical support for proactive health and intelligent healthcare.

Prenatal exposure to phthalates and childhood wheeze and asthma in the PROGRESS cohort

IntroductionPrenatal phthalate exposure may influence lung development and lead to wheezing and asthma in childhood, and these associations may vary by sex. Despite ubiquity of exposure, there is limited epidemiologic data on these associations in Latin America. MethodsWe assessed 593 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort in Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine. Report of ever wheeze, wheeze in the past 12 months (current wheeze) and ever asthma were obtained using a validated survey when children were 4 and 6 years of age. We examined individual associations with modified Poisson models. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. All models were adjusted for child's sex, maternal age and education at enrollment, and parity. ResultsIn Poisson models, a doubling of mono (carboxy-isononyl) phthalate (MCNP) during the 2nd trimester was associated with higher risk of wheeze (RR: 1.14, 95 % CI: 1.01, 1.29), and asthma (RR: 1.44, 95 % CI: 1.05, 1.97) at 4 years of age. Higher concentrations of the sum of di-isononyl phthalate metabolites (∑DiNP) during the 2nd trimester were also associated with asthma at 4 years of age (RR: 1.30, 95 % CI: 1.04, 1.61). Mixture associations of phthalate metabolite concentrations during the 2nd trimester and asthma at 4 years of age were stronger in males (BWQS, OR: 1.94, 95 % CI: 0.90, 4.60; 90 % CrI: 1.04, 3.73) compared to females (BWQS, OR: 1.23, 95 % CI: 0.56, 2.88; 90 % CrI: 0.61, 2.55). Additionally, we observed stronger inverse associations between prenatal phthalate mixtures during the 3rd trimester and current wheeze at 4 and 6 years of age in females (BWQS, OR: 0.54, 90 % CrI: 0.35, 0.82; OR: 0.45, 90 % CrI: 0.22, 0.84) compared to males (BWQS, OR: 0.95, 90 % Cri: 0.68, 1.35; OR: 0.97, 90 % CrI: 0.59, 1.54). ConclusionsPrenatal phthalate metabolite concentrations were associated with respiratory outcomes in childhood, with some evidence of sex specific effects. Future work investigating phthalate exposure and wheeze trajectories/lung function will be important for understanding how these may predict later disease.