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In this work, milk samples collected in a cohort of intensive dairy farms of the Po Valley (Italy) were screened for their (poly)-phenolic profile to check the occurrence of phenolic metabolites of biological interest. The selected dairy farms were previously classified on the basis of their cow feeding system, considering the utilization of corn silage as the main ingredient of the rations. Overall, ultra-high-pressure liquid chromatography coupled with mass spectrometry using an Orbitrap analyzer, followed by unsupervised and supervised statistics, allowed identifying clear different phenolic distributions in the milk samples. Accordingly, a great variability in the phenolic profiles of the different milk samples was observed, with two main phenolic clusters outlined by the unsupervised hierarchical clustering approach and not fully correlated to the nutritional strategy considered. The variables’ importance in the projection approach allowed selecting the most important metabolites, resulting in samples’ discrimination. Among the most discriminative compounds, we found phenolic metabolites (such as hippuric acid and 4-hydroxyhippuric acid), followed by lignans (such as enterolactone) and isoflavonoids (such as equol and O-desmethylangolensin). Taken together, our findings suggested that both the feeding systems and the ability of dairy cows to process parent phenolic compounds were the main factors providing the final (poly)-phenolic profile of the milk samples. Future targeted and ad hoc studies appear of great interest to evaluate the potential biological effects of these compounds on cow health.

Data on the evolution of blood metabolites and metabolic markers in neonatal piglets are scarce, although this information is vital to detect physiological aberrations from normal development. We aimed to characterize age- and nutrition-related changes in the plasma metabolome and serum biochemistry of suckling and newly weaned piglets and assess metabolite patterns as physiological markers for the two phases. In two replicate batches (n = 10 litters/group), piglets either received sow milk alone or were additionally offered creep feed from day 10 until weaning (day 28). Blood was collected from one piglet/litter on days 7, 14, 21, 28, 31 and 35 of life, totaling five females and five males/group/day. Signature feature ranking identified plasma triglycerides (TG) as discriminative for age and nutrition during the suckling phase. Influential TG 20:4_36:5, TG 17:0_34:2 and TG 18:2_38:6 were higher in creep-fed piglets on days 14, 21 and 28 of life, respectively, compared to only sow milk-fed piglets. Metabolites belonging to pathways within histidine, D-glutamine and D-glutamate metabolism as well as hippuric acid were distinctive for the postweaning compared to the suckling period. In conclusion, plasma lipid profiles especially corresponded to the type of nutrition in the suckling phase and showed a strong weaning effect.

Quantification of hippuric acid and methylhippuric acid in human urine matrices provides information on the toluene and xylene exposure conditions. High performance liquid chromatography coupled with UV detection is the preferable technique for hippuric acid and methylhippuric acid detection in human urine. This study was conducted to present analytical techniques developed for monitoring of hippuric acid and methylhippuric acid in human urine matrices during 2016–2021.

Extensive research has been carried out on the metabolomic changes in animal models of depression; however, there is no general agreement about which metabolites exhibit constant changes. Therefore, the aim of this study was to identify consistently altered metabolites in large-scale metabolomics studies of depression models. We performed vote counting analyses to identify consistently upregulated or downregulated metabolites in the brain, blood, and urine of animal models of depression based on 3743 differential metabolites from 241 animal metabolomics studies. We found that serotonin, dopamine, gamma-aminobutyric acid, norepinephrine, N-acetyl-L-aspartic acid, anandamide, and tryptophan were downregulated in the brain, while kynurenine, myo-inositol, hydroxykynurenine, and the kynurenine to tryptophan ratio were upregulated. Regarding blood metabolites, tryptophan, leucine, tyrosine, valine, trimethylamine N-oxide, proline, oleamide, pyruvic acid, and serotonin were downregulated, while N-acetyl glycoprotein, corticosterone, and glutamine were upregulated. Moreover, citric acid, oxoglutaric acid, proline, tryptophan, creatine, betaine, L-dopa, palmitic acid, and pimelic acid were downregulated, and hippuric acid was upregulated in urine. We also identified consistently altered metabolites in the hippocampus, prefrontal cortex, serum, and plasma. These findings suggested that metabolomic changes in depression models are characterized by decreased neurotransmitter and increased kynurenine metabolite levels in the brain, decreased amino acid and increased corticosterone levels in blood, and imbalanced energy metabolism and microbial metabolites in urine. This study contributes to existing knowledge of metabolomic changes in depression and revealed that the reproducibility of candidate metabolites was inadequate in previous studies.

Shujing Zhang,1,2,* Ping Luo,3,* Juanjuan Xu,1,* Lian Yang,4,* Pei Ma,1,* Xueyun Tan,1,* Qing Chen,5,* Mei Zhou,1 Siwei Song,1 Hui Xia,1 Sufei Wang,1 Yanling Ma,1 Fan Yang,4 Yu Liu,5 Yumei Li,1 Guanzhou Ma,1 Zhihui Wang,6 Yanran Duan,7 Yang Jin1 1Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 3Department of Translational Medicine Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 4Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 5Health Checkup Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 6Department of Scientific Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 7School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang JinDepartment of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of ChinaEmail whuhjy@126.comBackground: It remains unclear whether discharged COVID-19 patients have fully recovered from severe complications, including the differences in the post-infection metabolomic profiles of patients with different disease severities.Methods: COVID-19-recovered patients, who had no previous underlying diseases and were discharged from Wuhan Union Hospital for 3 months, and matched healthy controls (HCs) were recruited in this prospective cohort study. We examined the blood biochemical indicators, cytokines, lung computed tomography scans, including 39 HCs, 18 recovered asymptomatic (RAs), 34 recovered moderate (RMs), and 44 recovered severe/ critical patients (RCs). A liquid chromatography-mass spectrometry-based metabolomics approach was employed to profile the global metabolites of fasting plasma of these participants.Results: Clinical data and metabolomic profiles suggested that RAs recovered well, but some clinical indicators and plasma metabolites in RMs and RCs were still abnormal as compared with HCs, such as decreased taurine, succinic acid, hippuric acid, some indoles, and lipid species. The disturbed metabolic pathway mainly involved the tricarboxylic cycle, purine, and glycerophospholipid metabolism. Moreover, metabolite alterations differ between RMs and RCs when compared with HCs. Correlation analysis revealed that many differential metabolites were closely associated with inflammation and the renal, pulmonary, heart, hepatic, and coagulation system functions.Conclusion: We uncovered metabolite clusters pathologically relevant to the recovery state in discharged COVID-19 patients which may provide new insights into the pathogenesis of potential organ damage in recovered patients.Keywords: COVID-19, recovery, metabolomics

The removal of uremic toxins from patients with acute kidney injury is a key issue in improving the quality of life for people requiring peritoneal dialysis. The currently utilized method for the removal of uremic toxins from the human organism is hemodialysis, performed on semipermeable membranes where the uremic toxins, along with small molecules, are separated from proteins and blood cells. In this study, we describe a mixed-linker modulated synthesis of zirconium-based metal-organic frameworks for efficient removal of uremic toxins. We determined that the efficient adsorption of uremic toxins is achieved by optimizing the ratio between -amino functionalization of the UiO-66 structure with 75% of -NH2 groups within organic linker structure. The maximum adsorption of hippuric acid and 3-indoloacetic acid was achieved by UiO-66-NH2 (75%) and by UiO-66-NH2 (75%) 12.5% HCl prepared by modulated synthesis. Furthermore, UiO-66-NH2 (75%) almost completely adsorbs 3-indoloacetic acid bound to bovine serum albumin, which was used as a model protein to which uremic toxins bind in the human body. The high adsorption capacity was confirmed in recyclability test, which showed almost 80% removal of 3-indoloacetic acid after the third adsorption cycle. Furthermore, in vitro cytotoxicity tests as well as hemolytic activity assay have proven that the UiO-66-based materials can be considered as potentially safe for hemodialytic purposes in living organisms.

Previous research has indicated that various metabolites belonging to phenolic acids (PAs), produced by gut microflora through the breakdown of polyphenols, help in promoting bone development and protecting bone from degeneration. Results have also suggested that G-protein-coupled receptor 109A (GPR109A) functions as a receptor for those specific PAs such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA). Indeed, HA has a molecular structural similarity with nicotinic acid (niacin) which has been shown previously to bind to GPR109A receptor and to mediate antilipolytic effects; however, the binding pocket and the structural nature of the interaction remain to be recognized. In the present study, we employed a computational strategy to elucidate the molecular structural determinants of HA binding to GPR109A and GPR109B homology models in understanding the regulation of osteoclastogenesis. Based on the docking and molecular dynamics simulation studies, HA binds to GPR109A similarly to niacin. Specifically, the transmembrane helices 3, 4 and 6 (TMH3, TMH4 and TMH6) and Extracellular loop 1 and 2 (ECL1 and ECL2) residues of GRP109A; R111 (TMH3), K166 (TMH4), ECL2 residues; S178 and S179, and R251 (TMH6), and residues of GPR109B; Y87, Y86, S91 (ECL1) and C177 (ECL2) contribute for HA binding. Simulations and Molecular Mechanics Poisson-Boltzmann solvent accessible area (MM-PBSA) calculations reveal that HA has higher affinity for GPR109A than for GPR109B. Additionally, in silico mutation analysis of key residues have disrupted the binding and HA exited out from the GPR109A protein. Furthermore, measurements of time-resolved circular dichroism spectra revealed that there are no major conformational changes in the protein secondary structure on HA binding. Taken together, our findings suggest a mechanism of interaction of HA with both GPR109A and GPR109B receptors.

Magistrska naloga predstavlja sintezo novih 3-benzoilamino-2H-piran-2-onov iz različnih monokarbonilnih spojin z aktivirano metilno skupino. V uvodnem delu je opisana razširjenost in pomen 2H-piran-2-onov v naravi, za kaj so koristni in kako jih pripravimo. Na kratko so opisane kemijske in spektroskopske značilnosti 2H-piran-2-onov ter kako jih lahko uporabimo v nadaljnjih reakcijah. Eksperimentalni del opisuje sintezo novih 3-benzoilamino-2H-piran-2-onov po dvostopenjski »one pot« metodi. V prvi stopnji sem izhodno monokarbonilno spojino segrevala ob prisotnosti DMFDMA (v vlogi C1-sintona). Nastalo zmes sem destilirala pod znižanim tlakom in nato temu enaminonskemu intermediatu dodala hipurno kislino in acetanhidrid, ki in situ reagirata v oksazolonski derivat. Zopet je sledilo segrevanje nato pa izolacija (obarjanje) in čiščenje dobljenih 3-benzoilamino-2H-piran-2-onov. Končne spojine sem analizirala s TLC, IR, 1H NMR in MS. Medsebojna primerjava analiz produktov razkriva razlike v njihovi reaktivnosti in izkoristkih. The Master's thesis presents the synthesis of new 3-benzoylamino-2H-pyran-2-ones from various monocarbonyl compounds with an activated methyl group. The introductory part describes where 2H-pyran-2-ones are found in nature, their importance and applications as well as how they are prepared. The chemical and spectroscopic characteristics of 2H-pyran-2-ones and how they can be used in further transformations are also briefly described. The experimental part describes the synthesis of new 3-benzoylamino-2H-pyran-2-ones by the one pot method, consisting of two steps. In the first step the starting monocarbonyl compound was heated in the presence of DMFDMA (acting as a C1-synthon). Distillation of the resulting mixture under reduced pressure and the addition of hippuric acid and acetic anhydride (in situ forming oxazolone derivative) to this enaminone intermediate with additional heating, followed by isolation (precipitation) and purification gave the final products 3-benzoylamino-2H-pyran-2-ones. I analyzed the final compounds by TLC, IR, 1H NMR and MS. Comparison of products and their analyses reveals the differences in reactivity and influences on the yields.

Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to adverse health outcomes, and poor quality of life. This study was conducted in the framework of InveCe.Ab, an ongoing longitudinal population-based study. Plasma from 130 older individuals (older adults aged 76–78 years) was analyzed and validated (on 303 participants) using mass spectrometry-based metabolomics approaches. Equivalence tests showed that metabolites from the central cellular metabolic pathways were equivalent in frail and fit participants. Hippuric acid was the only cometabolite that distinguished fit from frail older adults. Logistic regression analysis indicated that high hippuric acid levels are significantly associated with a reduction of the risk of frailty after 4 years. Mediation analysis using a Frailty Index, hippuric acid, and fruit–vegetable intake supported the role of fruit–vegetable consumption in the hippuric acid relationship with the Frailty Index. These data point to low plasma hippuric acid as a plausible hallmark of frailty status, associated with lower fruit–vegetable intakes.

Phenylketonuria (PKU) is a rare disease caused by biallelic mutations in the PAH gene that result in an inability to convert phenylalanine (Phe) to tyrosine, elevated blood Phe levels and severe neurological complications if untreated. Most patients are unable to adhere to the protein-restricted diet, and thus do not achieve target blood Phe levels. We engineered a strain of E. coli Nissle 1917, designated SYNB1618, through insertion of the genes encoding phenylalanine ammonia lyase and l-amino acid deaminase into the genome, which allow for bacterial consumption of Phe within the gastrointestinal tract. SYNB1618 was studied in a phase 1/2a randomized, placebo-controlled, double-blind, multi-centre, in-patient study ( NCT03516487 ) in adult healthy volunteers (n = 56) and patients with PKU and blood Phe level ≥600 mmol l−1 (n = 14). Participants were randomized to receive a single dose of SYNB1618 or placebo (part 1) or up to three times per day for up to 7 days (part 2). The primary outcome of this study was safety and tolerability, and the secondary outcome was microbial kinetics. A D5-Phe tracer (15 mg kg−1) was used to study exploratory pharmacodynamic effects. SYNB1618 was safe and well tolerated with a maximum tolerated dose of 2 × 1011 colony-forming units. Adverse events were mostly gastrointestinal and of mild to moderate severity. All participants cleared the bacteria within 4 days of the last dose. Dose-responsive increases in strain-specific Phe metabolites in plasma (trans-cinnamic acid) and urine (hippuric acid) were observed, providing a proof of mechanism for the potential to use engineered bacteria in the treatment of rare metabolic disorders. Puurunen et al. demonstrate the safety and tolerability in patients with phenylketonuria of a genetically modified strain of E. coli encoding metabolic enzymes to metabolize phenylalanine to non-toxic metabolites.

Background: The purpose of this study was to determine the concentration levels of hippuric acid and 2, 3, 4- methyl hippuric acid isomers as biological indicators of exposure to toluene and xylene isomers in the urine of the gas stations workers of Ahvaz, Iran.Methods: The urine sample was taken the first time in January and the second time in June 2018. Eight gas stations were selected in Ahvaz, Khuzestan Province, Iran. The study sample was 24 males; three workers participated in the study from each gas station. Two workers in each gas station served as the exposed group, and one secretary from each gas station was the control group. The participants’ ages ranged from 21 to 49 years. Each participant was requested to fill out a consent form to participate in the study and a questionnaire containing personal information such as age, smoking, weight and height, and work experience.Results: The mean concentration of hippuric acid, 2, 3 and 4- methyl hippuric acid in the investigated urine of the workers were 0.245, 0.017, 0.012, and 0.011 g/g creatinine, respectively. There was no relationship between variable of season and levels of hippuric acid, 2, 3 and 4- methyl hippuric acid in the urine of exposed and control groups.Conclusion: There was no significant difference in the analyzed results of urine samples between control and exposure groups. There was at least one methyl hippuric acid isomer, indicating that all subjects were exposed to xylene, which was lower than the threshold limit value. In conclusion, the variable of season cannot cause a significant change in the metabolites of toluene and xylene isomers. Exposure of workers to toluene and xylene at gas stations is within acceptable limits.

Functional dyspepsia (FD) is a common disease of the digestive system and probiotics have been reported to be effective in the treatment of functional gastrointestinal diseases. The aim of this study was to determine the effect of the beverage containing Lactobacillus paracasei LC-37 (LC-37) and its ability to relieve symptoms of FD by a randomized clinical trial. Due to the mechanistic complexity underlying FD, intestinal microbiota and stool metabolomes were also evaluated. The results showed that FD was relieved in participants after treatment with the beverage containing LC-37 for 14 and 28 d. The clinical symptom scores were significantly decreased after these times (abdominal pain and belching were significantly decreased after 14 d and almost absent after 28 d of treatment). Probiotics, such as those containing the Lactobacillus, Lactococcus, and Weissella, significantly increased, and the abundance of harmful bacteria such as Lachnocliostridium significantly decreased. Furthermore, relevant beneficial intestinal metabolites such as pelargonic acid, benzoic acid, and short-chain fatty acids increased, and harmful intestinal metabolites such as hippuric acid decreased. Taken together, these findings suggested that the beverages containing LC-37 can increase the abundance of probiotics and decrease pathogenic bacteria, and thereby improve beneficial intestinal metabolites. Therefore, the beverages containing LC-37 may provide a natural alternative to combat FD.

Synthetic Nitrogen Base Analogues (SNBA) fused heterocyclic purine and pyrimidine derivatives are of great biological interest, especially as antiviral, antitumor and antimicrobial agents. The viruses are one of the risk factors for plants resulting in gigantic economic losses . Four SNBA compounds were assayed antiviral activity, plant cytotoxicity as well as determining their mode of action against Tomato mosaic tobamovirus (ToMV) by using the local lesion on Datura metel as well as infectivity assayed on tomato plants . The cytotoxicity of Ph-Oxanzolo and Oxazalone compounds at concentrations 15 and 20μg/mL showed chlorosis, mottling, necrosis, wilting, and curling at three to four days after spraying while Hippuric acid and Benzotriazolo compounds were safe on test plants and didn’t show any signs of toxicity on D.metel and tomato plants . Ph-Oxanzolon and Oxazalone had virucidal activity where showed high percentage of inhibition at simultaneous- ToMV inoculation at 5,10,15,20 ppm concentration and low percentage of inhibition at pre-and –post ToMV inoculation , as well as they showed high ToMV concentration and low percentage disease severity at 10 ppm concentration . While another Hippuric acid and Benzotriazol had affect the ToMV replication process , where showed weak inhibitory activity of inhibition at simultaneous - ToMV inoculation at 5,10,15,20 ppm concentration and low percentage of inhibition at pre-and –post ToMV inoculation , as well as they showed very low doubtful ToMV concentration and disease severity percentage at 15 ppm concentration .

Metabolites of β2-agonists 2-(4-amino-3,5-dichlorophenyl)-2-(alkylamino)ethanols, derivatives of hippuric and mandelic acids, were synthesized. The excretion profiles of the target compounds and metabolites with urine were studied in experiments on laboratory animals. 2-(4-Amino-3,5-dichlorophenyl)-2-(isopropylamino) ethanol (9.7% of the administered dose) and 2-(4-amino-3,5-dichlorophenyl)-2-(tert-amylamino)ethanol (0.7%) were isolated unchanged after a single peroral administration of the compounds at doses of 270 and 540 μg/kg. The times for determination of the target components and metabolites in urine of laboratory animals at a method sensitivity of 0.1 ng/mL were established as 120 h after administration for 2-(4-amino-3,5-dichlorophenyl)-2-(isopropylamino)ethanol and 96 h for 2-(4-amino-3,5-dichlorophenyl)-2-(tert-amylamino)ethanol. The metabolite of 2-(4-amino-3,5-dichlorophenyl)-2-(tert-amylamino)ethanol, a hippuric acid derivative, was detected in urine longer (120 h) than the initial compound.

Spot urinary polyphenols have potential as a biomarker of polyphenol-rich food intakes. The aim of this study is to explore the relationship between spot urinary polyphenols and polyphenol intakes from polyphenol-rich food sources. Young adults (18–24 years old) were recruited into a sub-study of an online intervention aimed at improving diet quality. Participants’ intake of polyphenols and polyphenol-rich foods was assessed at baseline and 3 months using repeated 24-h recalls. A spot urine sample was collected at each session, with samples analysed for polyphenol metabolites using LC-MS. To assess the strength of the relationship between urinary polyphenols and dietary polyphenols, Spearman correlations were used. Linear mixed models further evaluated the relationship between polyphenol intakes and urinary excretion. Total urinary polyphenols and hippuric acid (HA) demonstrated moderate correlation with total polyphenol intakes (rs = 0·29–0·47). HA and caffeic acid were moderately correlated with polyphenols from tea/coffee (rs = 0·26–0·46). Using linear mixed models, increases in intakes of total polyphenols or polyphenols from tea/coffee or oil resulted in a greater excretion of HA, whereas a negative relationship was observed between soya polyphenols and HA, suggesting that participants with higher intakes of soya polyphenols had a lower excretion of HA. Findings suggest that total urinary polyphenols may be a promising biomarker of total polyphenol intakes foods and drinks and that HA may be a biomarker of total polyphenol intakes and polyphenols from tea/coffee. Caffeic acid warrants further investigation as a potential biomarker of polyphenols from tea/coffee.

This cross-sectional study aimed to assess the adverse effects of benzene and toluene exposure in gasoline station workers via biological screening and health risk assessment. Ambient air benzene a...

Metabolites of β2-agonists of 2-(4-amino-3,5-dichlorophenyl)-2-(alkylamino)ethanols, derivatives of hippuric and mandelic acids, have been synthesized. In experiments on laboratory animals, the excretion profile of target compounds and metabolites with urine was studied. After single oral administration of drugs in doses of 270 and 540 mg/kg, 9.7% of 2-(4-amino-3,5-dichlorophenyl)-2-(isopropylamino)ethanol and 0,7 % of 2-(4-amino-3,5-dichlorophenyl)-2-( tert -amylamino)ethanol from the administered dose were isolated in unchanged form. The times for determination of target components and metabolites in the urine of laboratory animals at the method sensitivity of 0.1 ng/mL has been established: 2-(4-amino-3,5-dichlorophenyl)-2-(isopropylamino)ethanol is identified for more than 120 h after drug taking and 2-(4-amino-3,5-dichlorophenyl)-2-( tert -amylamino)ethanol is identified for 96 h. Metabolite of 2-(4-amino-3,5-dichlorophenyl)-2-( tert -amylamino)ethanol (derivative of hippuric acid) is detected in urine longer than the initial compound – for more than 120 h.

Non linear optical single crystals of pure and Sodium acid phthalate doped Hippuric acid (SAPHA) crystals were grown in room temperature by slow evaporation method, with the vision to improve the properties of the crystals. Intensities of Powder X-ray diffraction peaks of sodium acid phthalate doped HA reveal that these dopants enhanced the crystallinity. The FTIR analysis is used to study the functional groups. The UV–Visible analysis is used to find the level of transmission and range of absorption of the crystals. The second harmonic generation (SHG) crystal was tested by Kurtz and Perry powder method using Nd:YAG laser and the result confirms that the grown crystal has SHG efficiency 1.05 times more than KDP crystal. The fluorescence study performed for pure and doped HA crystal. The Thermogravimetric analysis confirms the stability of grown crystals. The dielectric response of title crystal was analyzed in the frequency range of 10–100 kHz for four different temperatures at 32 °C, 50 °C, 75 °C, and 100 °C. The hardness of the crystals was determined by Vicker’s Microhardness test.

Blueberries (BB) contain an array of bioactive phenolic compounds that may play a protective role against various age-related diseases. Here we explored the metabolic fate of BB phenolics and their relationship to cognitive function after chronic (90 days) supplementation of freeze-dried BB (24 g d-1, equivalent to 1 cup of fresh BB) or control in a randomized, double-blind, parallel study with 38 healthy older adults (60-75 years). Blood samples were collected at fasting (t = 0 h) and 2 h after a breakfast meal on days 0 (no treatment), 45, and 90, and a battery of cognitive tests was also conducted on these days. Hippuric acid, phloroglucinaldehyde, syringic acid, ferulic acid-glucuronide, cyanidin-3-O-galactoside, cyanidin-3-O-glucoside, malvidin-3-O-galactoside, malvidin-3-O-glucoside, peonidin-3-O-xyloside, peonidin glucuronide, and petunidin-3-O-glucoside concentrations were significantly altered after 90 days of BB consumption compared to control. Stepwise regression was used to assess the relationship between significantly altered concentrations of plasma phenolics and observed improvements in cognition. Among participants in the BB group, changes in switch errors on the task-switching test (TST) from day 0 to 90 were associated with changes in postprandial levels of plasma ferulic acid-glucuronide, syringic acid, and malvidin-3-galactoside (R2 = 0.521, p < 0.05). Changes in repetition errors on the California Verbal Learning Test (CVLT-II) from day 0 to 90 were associated with changes in postprandial levels of ferulic acid-glucuronide, syringic acid, and hippuric acid (R2 = 0.807, p < 0.001). These findings demonstrate that the addition of easily achievable quantities of BB to the diets of older adults significantly alters levels of circulating phenolic compounds which are related to improvements in cognition.

In this study, the content of hippuric and benzoic acid of goat milk kefir produced with commercial lyophilized kefir cultures and kefir grain was investigated. 9 commercial kefir culture and 1 kefir grain were used in production of goat milk kefir. Based on the obtained results, hippuric acid was not found in kefir samples during the storage period, whereas goat milk samples contained hippuric acid (14.8 mg/kg). Benzoic acid levels of kefir samples ranged from 8.5 to 26.6 mg/kg during the 28-day storage period. The highest Lactobacillus and Lactococcus counts were observed in kefir sample produced with kefir grain while this sample was one of the sample containing the lowest (11.2 mg/kg) benzoic acid levels. In conclusion, the research results showed that starter kefir cultures and microbiota used in kefir production and storage period had a significant effect on the formation of benzoic acid levels (p

Albumin binding is the major cause for the toxicity of protein bound uremic toxins (PBUTs) in uremic patients. Albumin binding property is exploited to address this issue, as some of the extracorporeal dialysis systems use albumin as dialysate. In this line, a detailed study about binding of PBUTs to human serum albumin (HSA) and its domains gives valuable information. The focus of this work emphasizes the mechanism of binding of HSA and its domains with a few selected PBUTs such as hippuric acid (HA), indole acetic acid (IAA) and melatonin. The HSA domains (D2, D3 and D2–3) were expressed in Pichia pastoris and purified by using Albupure matrix. The binding of the expressed domains and HSA, with PBUTs, was measured using surface plasmon resonance and analyzed. All the three domains have significant affinity towards PBUTs, while D3 had greater affinity for all the three selected PBUTs. Docking studies showed that the basic amino acid, lysine, was forming hydrogen bond with PUBTs inorder to stabile these complex. This study would be having therapeutic importance for preparing the extracorporeal dialysis systems, in combination of different domains of HSA to remove the PBUTs.

Background Bisphenol S (BPS) is a structural analogue of bisphenol A (BPA) that is found in the environment. BPS may accumulate in anuric patients due to decreased urinary excretion. The toxicity and health effects of BPS are poorly characterized. Methods A cross-over study was performed using polynephron (PN) or polysulphone (PS) dialysers for a short (1 week each, 14 patients) or long (3 months each, 20 patients) period on each dialyser. Plasma BPA, BPS and hippuric acid were assessed by SRM mass spectrometry (SRM-MS). The biological significance of the BPS concentrations found was explored in cultured kidney tubular cells. Results In haemodiafiltration (HDF) patients, plasma BPS was 10-fold higher than in healthy subjects (0.53 ± 0.52 versus 0.05 ± 0.01 ng/mL; P = 0.0015), while BPA levels were 35-fold higher (13.23 ± 14.65 versus 0.37 ± 0.12 ng/mL; P = 0.007). Plasma hippuric acid decreased after an HDF session, while BPS and BPA did not. After 3 months of HDF with the same membranes, the BPS concentration was 1.01 ± 0.87 ng/mL for PN users and 0.62 ± 0.21 ng/mL for PS users (P non-statistically significant). In vitro, BPS and BPA leaked from dialysers containing them. In cultured tubular cells, no biological impact (cytotoxicity, inflammatory and oxidative stress gene expression) was observed for BPS up to 200 µM, while BPA was toxic at concentrations ≥100 µM. Conclusions BPS may be released from dialysis membranes, and dialysis patients display high BPS concentrations. However, BPS concentrations are lower than BPA concentrations and no BPS toxicity was observed at concentrations found in patient plasma.

Renal energy losses of horses are high in comparison with other species. In the present study, more data were obtained on this parameter to improve predictive equations for renal energy losses. Four adult ponies (247-344 kg body weight [BW]) were fed with eight different diets based on first cut hay, second cut hay, early first cut fresh grass, late cut herbs-grass mix, early cut clover-grass mix, sugar beet pulp, rice bran and straw. Feed intake was measured, and urine and faeces were quantitatively collected for 3 × 12 hr at daytime and afterwards 3 × 12 hr at nighttime. Feed was analysed for crude nutrients, gross energy, amino acids and neutral-detergent-insoluble crude protein (NDICP); faeces were analysed for crude nutrients and gross energy; and urine was analysed for nitrogen (N) and gross energy. Renal energy losses per gram dry matter (DM) intake (y; kJ/g DM) were strictly correlated to protein content in DM (x; g/kg DM): y = 0.325 + 0.00431x; r2 = .81; n = 38; p

Objective Depression could make the treatment outcome worse. However, up to now, no objective methods were developed to diagnose depression in hepatitis B virus (HBV)-infected patients. Therefore, the dual metabolomic platforms were used here to identify potential biomarkers for diagnosing HBV-infected patients with depression (dHB). Methods Both gas chromatography-mass spectrometry-based and nuclear magnetic resonance-based metabolomic platforms were used to conduct urine metabolic profiling of dHB subjects and HBV-infected patients without depression (HB). Orthogonal partial least-squares discriminant analysis was used to identify the differential metabolites between dHB subjects and HB subjects, and the step-wise logistic regression analysis was used to identify potential biomarkers. Results In total, 21 important metabolites responsible for distinguishing dHB subjects from HB subjects were identified. Meanwhile, seven potential biomarkers (α-ydroxyisobutyric acid, hippuric acid, azelaic acid, isobutyric acid, malonic acid, levulinic acid, and phenylacetylglycine) were viewed as potential biomarkers. The simplified biomarker panel consisting of these seven metabolites had an excellent diagnostic performance in discriminating dHB subjects from HB subjects. Moreover, this panel could yield a higher accuracy in separating dHB subjects from HB subjects than our previous panels (identified by single metabolomic platform) did. Conclusion These results suggested that the dual metabolomic platforms could yield a better urinary biomarker panel for dHB subjects than any single metabolomic platform did, and our results could be helpful for developing an objective method in future to diagnose depression in HBV-infected patients.

This study aimed to evaluate the effects of different feedings on main traits and polar and semi-polar metabolite profiles of ovine milk. The milk metabolome of two groups of Sarda sheep kept under different grazing systems were analyzed by gas chromatography coupled with mass spectrometry (GC-MS) and multivariate statistical analysis (MVA). The results of discriminant analysis indicated that the two groups showed a different metabolite profile, i.e., milk samples of sheep kept under Grazing System 1 (GS1) were richer in nucleosides, inositols, hippuric acid, and organic acids, while milk of sheep under Grazing System 2 (GS2) showed higher levels of phosphate. Statistical analysis of milk main traits indicates that fat content was significantly higher in GS1 samples while milk from GS2 sheep had more urea, trans-vaccenic acid, and rumenic acid. MVA studies of the associations between milk main traits and metabolite profile indicated that the latter reflects primarily the long chain fatty acid content, the somatic cell count (SCC), and lactose levels. All together, these results demonstrated that an integrated holistic approach could be applied to deepen knowledge about the effects of feeding on sheep’s milk composition.

Potentiometric titrations have been used to calculate the dissociation constants of Hippuric acid and its stability constants with Cu(II), Ni(II), Zn(II), and Pb(II) ions in ethanol-water mixed solvent system at different temperatures, and constant ionic strength of 0.1M solution sodium nitrate. The order of the stability constants of metal complexes at 298 K with respect to ligand was found to be Cu(II) > Pb(II) > Zn(II) > Ni(II). Effect of temperature on stability of hippuric acid complexes with Cu(II) and Pb(II) has been studied in order to calculate the Gibb`s free energy and enthalpy of the complex formation reaction, the results showed that coordination process is spontanous and exothermic. Effect of solvent ratio has been studied only for Cu(II) complex and the dissociation of hippuric acid at given added different ratios decreases on the following order 75% > 50%.

Background: Key pathogenetic mechanisms underlying renal disease progression are unaffected by current treatment. Metabolite profiling has significantly contributed to a deeper understanding of the biochemical metabolic networks and pathways in disease, but the biochemical details in maintenance hemodialysis (MHD) patients remain largely undefined. Methods: The metabolic fingerprinting of plasma samples from 19 MHD patients and 12 healthy controls was characterized using liquid chromatography quadrupole time-of-flight mass spectrometry. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to analyze the metabolic data. Results: The plasma metabolite profile distinguished the MHD patients from the healthy controls successfully by using both PCA and OPLS-DA models. Sixty-three metabolites were identified as the key metabolites to discriminate the MHD patients from healthy controls, involving several metabolic pathways (all p < 0.05). An increase in plasma levels of D-glucose, hippuric acid, androsterone glucuronide, indolelactic acid, and a reduction in plasma levels of glycerophosphocholine, serotonin, L-lactic acid, phytosphingosine, and several lysophosphatidylcholine were observed in MHD patients compared to healthy subjects. Metabolomics analysis combined with KEGG pathway enrichment analysis revealed that non-alcoholic fatty liver disease, choline metabolism in cancer, the forkhead box O signaling pathway, and the hypoxia-inducible factor-1 signaling pathway in MHD patients were significantly changed (p < 0.05). Conclusion: The identification of a novel signaling pathway and key metabolite markers in MHD patients provides insights into potential pathogenesis and valuable pharmacological targets for end-stage renal disease.

The comparison of non-caloric sweeteners (stevia and sucralose) and sucrose, on the plasma concentration and cumulative effects of phenolic compounds, was achieved. A long-term intervention, consisting of the daily intake of 330 mL of healthy citrus-maqui soft drinks, for 60 days, by 138 healthy overweight adults, was followed. A total of 24 bioavailable metabolites derived from caffeic acid, 3,4-di-hydroxyphenylacetic acid, eriodictyol, homoeriodictyol, hippuric acid, naringenin, 2,4,6-tri-hydroxybenzaldehyde, and vanillic acid were detected in peripheral blood plasma. A similar augment of bioactive compounds in plasma concentrations were found for the three beverages, in the range 12.3% (day 0)- 85.3% (day 60), depending on the analyte considered. Due to this, the present study highlights sucralose and stevia as valuable alternatives to sucrose, providing and non-significantly different plasma concentration and cumulative effect in the plasma, thus contributing to prevent a diversity of metabolic disorders and health constraints., This research was funded by the Spanish MINECO, grant number (AGL2016-75332-C2-1-R AEI / FEDER UE and PID2019-104212RB-I00/ AEI/ 10.13039 / 501100011033). VA was supported by an FPI grant (BES-2017-082424)

The development of complex biological sample-compatible fluorescent molecularly imprinted polymers (MIPs) with improved performances is highly important for their real-world bioanalytical and biomedical applications. Herein, we report on the first hydrophilic “turn-on”-type fluorescent hollow MIP microparticles capable of directly, highly selectively, and rapidly optosensing hippuric acid (HA) in the undiluted human urine samples. These fluorescent hollow MIP microparticles were readily obtained through first the synthesis of core-shell-corona-structured nitrobenzoxadiazole (NBD)-labeled hydrophilic fluorescent MIP microspheres by performing one-pot surface-initiated atom transfer radical polymerization on the preformed “living” silica particles and subsequent removal of their silica core via hydrofluoric acid etching. They showed “turn-on” fluorescence and high optosensing selectivity and sensitivity toward HA in the artificial urine (the limit of detection = 0.097 μM) as well as outstanding photostability and reusability. Particularly, they exhibited much more stable aqueous dispersion ability, significantly faster optosensing kinetics, and higher optosensing sensitivity than their solid counterparts. They were also directly used for quantifying HA in the undiluted human urine with good recoveries (96.0%–102.0%) and high accuracy (RSD ≤ 4.0%), even in the presence of several analogues of HA. Such fluorescent hollow MIP microparticles hold much promise for rapid and accurate HA detection in the clinical diagnostic field.

Objective: Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota dysbiosis is closely related to renal damage and fibrosis, we investigated the role of gut microbiota and microbiota-related serum metabolites in DKD progression in this study.Methods: Fecal and serum samples obtained from predialysis DKD patients from January 2017 to December 2019 were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Forty-one predialysis patients were divided into two groups according to their estimated glomerular filtration rate (eGFR): the DKD non-ESRD group (eGFR ≥ 15 ml/min/1.73 m2) (n = 22), and the DKD ESRD group (eGFR < 15 ml/min/1.73 m2) (n = 19). The metabolic pathways related to differential serum metabolites were obtained by the KEGG pathway analysis. Differences between the two groups relative to gut microbiota profiles and serum metabolites were investigated, and associations between gut microbiota and metabolite concentrations were assessed. Correlations between clinical indicators and both microbiota-related metabolites and gut microbiota were calculated by Spearman rank correlation coefficient and visualized by heatmap.Results: Eleven different intestinal floras and 239 different serum metabolites were identified between the two groups. Of 239 serum metabolites, 192 related to the 11 different intestinal flora were mainly enriched in six metabolic pathways, among which, phenylalanine and tryptophan metabolic pathways were most associated with DKD progression. Four microbiota-related metabolites in the phenylalanine metabolic pathway [hippuric acid (HA), L-(−)-3-phenylactic acid, trans-3-hydroxy-cinnamate, and dihydro-3-coumaric acid] and indole-3 acetic acid (IAA) in the tryptophan metabolic pathway positively correlated with DKD progression, whereas L-tryptophan in the tryptophan metabolic pathway had a negative correlation. Intestinal flora g_Abiotrophia and g_norank_f_Peptococcaceae were positively correlated with the increase in renal function indicators and serum metabolite HA. G_Lachnospiraceae_NC2004_Group was negatively correlated with the increase in renal function indicators and serum metabolites [L-(−)-3-phenyllactic acid and IAA].Conclusions: This study highlights the interaction among gut microbiota, serum metabolites, and clinical indicators in predialysis DKD patients, and provides new insights into the role of gut microbiota and microbiota-related serum metabolites that were enriched in the phenylalanine and tryptophan metabolic pathways, which correlated with the progression of DKD.

Angiotensin converting enzyme (ACE) plays a crucial role in regulating blood pressure in the human body. Identification of potential ACE inhibitors from medicinal plants supported the idea of repurposing these medicinal plants against hypertension. A method based on ultra-performance liquid chromatography (UPLC) coupled with a diode array detector (DAD) was used for the rapid screening of plant extracts and purified compounds to determine their ACE inhibitory activity. Hippuryl-histidiyl-leucine (HHL) was used as a substrate, which is converted into hippuric acid (HA) by the action of ACE. A calibration curve of the substrate HHL was developed with the linear regression 0.999. The limits of detection and quantification of this method were found to be 0.134 and 0.4061 mM, respectively. Different parameters of ACE inhibitory assay were optimized, including concentration, incubation time and temperature. The ACE inhibition potential of Adhatoda vasica (methanolic-aqueous extract) and its isolated pyrroquinazoline alkaloids, vasicinol (1), vasicine (2) and vasicinone (3) was evaluated. Compounds 1–3 were characterized by various spectroscopic techniques. The IC50 values of vasicinol (1), vasicine (2) and vasicinone (3) were found to be 6.45, 2.60 and 13.49 mM, respectively. Molecular docking studies of compounds 1–3 were also performed. Among these compounds, vasicinol (1) binds as effectively as captopril, a standard drug of ACE inhibition.

El objetivo de este estudio piloto fue evaluar el efecto de ácido ferúlico (AF) sobre el comportamiento productivo y metabolitos en orina en becerros de destete precoz. 29 becerros aleatoriamente distribuidos en 4 corrales (2 corrales por tratamiento). Los tratamientos: control y AF (10 ppm kg-1 peso vivo) por 30 días. Se registraron los pesos de los animales, se colectaron muestras de orina, al incio y final de la suplementación y el consumo de alimento se registró diariamente. Se determinaron los metabolitos en orina por HPLC-DAD. No se encontraron efectos en el comportamiento productivo (p >0.05). No se encontró presencia de AF, trans-isoferúlico ni de sus conjugados en la orina, solo la excreción de ácido hipúrico (AH) aumentó en el grupo suplementado con AF (282.97µg/ml) respecto al grupo control (133µg/ml). Los resultados sugieren que AF podría ser excretado como AH y que no ocurre una acumulación de AF.

Chronic kidney disease (CKD) is characterized by the accumulation of uremic toxins which exert deleterious effects on various organ systems. Several of these uremic toxins originate from the bacterial metabolization of aromatic amino acids in the colon. This study assessed whether the gut microbial composition varies among patients in different stages of CKD. Uremic metabolites were quantified by UPLC/fluorescence detection and microbial profiling by 16S rRNA amplicon sequencing. Gut microbial profiles of CKD patients were compared among stages 1-2, stage 3 and stages 4-5. Although a substantial inter-individual difference in abundance of the top 15 genera was observed, no significant difference was observed between groups. Bristol stool scale (BSS) correlated negatively with p-cresyl sulfate and hippuric acid levels, irrespective of the intake of laxatives. Butyricicoccus, a genus with butyrate-generating properties, was decreased in abundance in advanced stages of CKD compared to the earlier stages (p = 0.043). In conclusion, in this cross-sectional study no gradual differences in the gut microbial profile over the different stages of CKD were observed. However, the decrease in the abundance of Butyricicoccus genus with loss of kidney function stresses the need for more in-depth functional exploration of the gut microbiome in CKD patients not on dialysis. ispartof: JOURNAL OF PERSONALIZED MEDICINE vol:11 issue:11 ispartof: location:Switzerland status: published

The alkaline hydrolysis of jD-nitrophenyl hippurate occurs in two steps. In the first step, which is subject to general-base catalysis, p-nitrophenol is released and 2-phenyl-oxazolin-5-one is formed. Subsequent hydrolysis of this oxazolinone yields hippuric acid. An investigation of the kinetics of hydrolysis of a series of esters of N-acyl amino acids revealed that oxazolinone intermediates are formed from activated esters but not from stable e s te rs . No oxazolinone intermediate could be observed in the deacylation of hippuryl-chymotrypsin, indicating that the acyl-enzyme behaves as a stable, rather than as an activated, ester of hippuric acid. The spontaneous and enzyme-catalysed hydrolyses of a number of saturated oxazolinones have been investigated. The rate constants obtained show the high reactivity of the oxazolinone carbonyl carbon towards nucleophilic attack.

Chronic kidney disease (CKD) is characterized with the influx of uremic toxins, which impairs the gut microbiome by decreasing beneficial bacteria that produce short-chain fatty acids (SCFAs) and increasing harmful bacteria that produce gut-derived protein-bound uremic toxins (PBUTs). This study aimed to assess the proapoptotic effects of three major gut-derived PBUTs in hepatocytes, and the effects of SCFAs on apoptosis phenotype in vitro. HepG2 (human liver carcinoma cells) and THLE-2 (immortalized human normal liver cells) cell line were incubated with 0, 2, 20, 200, 2000 μM p-cresol sulfate (PCS), indoxyl sulfate (IS), and hippuric acid (HA), respectively, for 24 h. Flow cytometry analysis indicated that three uremic toxins induced varying degrees of apoptosis in hepatocytes and HA represented the highest efficacy. These phenotypes were further confirmed by western blot of apoptosis protein expression [Caspase-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax)]. Human normal hepatocytes (THLE-2) are more sensitive to PBUTs-induced apoptosis compared with human hepatoma cells (HepG2). Mechanistically, extracellular HA could enter hepatocytes, increase reactive oxygen species (ROS) generation, and decrease mitochondrial membrane potential dose-dependently in THLE-2 cells. Notably, coculture with SCFAs (acetate, propionate, butyrate) for 24 h significantly improved HA-induced apoptosis in THLE-2 cells, and propionate (500 μM) represented the highest efficacy. Propionate reduction of apoptosis was associated with improving mitochondria dysfunction and oxidative stress in a manner involving reducing Caspase-3 expression, ROS production, and increasing the Bcl-2/Bax level. As such, our studies validated PBUTs accumulation might be an important cause of liver dysfunction in patients with CKD, and supplementation of SCFAs might be a viable way to protect the liver for patients with CKD.

Psoraleae Fructus (PF) is a botanical medicine widely used in Asian countries, of which salt products have higher safety and efficacy. However, the biological mechanism of the detoxification of salt-processing Psoraleae Fructus (SPF) has not yet been revealed. In this study, UPLC-MS/MS technology was used to explore the metabolic differences between SPF and PF in normal rats and reveal the mechanism of salt processing. The histopathological results of rat liver and kidney showed that the degree of liver and kidney injure in the SPF group was less than that in the PF group. The results of metabolomics showed that the detoxification mechanism of PF by salt processing might be related to glycerophospholipid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, arginine and proline metabolism, phenylalanine metabolism, and linoleic acid metabolism. PF-induced inflammation could be reduced by regulating the expression of metabolites to achieve the purpose of salt processing and detoxification. It included reducing the production of metabolites such as 1-acyl-sn-glycero-3-phosphocholine, sn-glycero-3-phosphocholine, tyrosine, arginine, linoleic acid, arachidonic acid, and phenylacetylglycine/hippuric acid ratio and upregulating the expression of metabolites such as creatine.

Introduction: Protein-bound uraemic toxins (PBUTs) are poorly removed by conventional dialytic techniques, given their high plasma protein binding, and thus low, free (dialysable) plasma concentration. Here, we evaluated and compared PBUTs removal among conventional haemodialysis (HD), adsorption-based HD, displacement-based HD, and their 2 combinations both in vitro and in vivo. Methods: The removal of PBUTs, including 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresyl sulphate (PCS), indoxyl sulphate (IS), indole-3-acetic acid (3-IAA), and hippuric acid, was first evaluated in an in vitro single-pass HD model. Adsorption consisted of adding 40 g/L bovine serum albumin (Alb) to the dialysate and displacement involved infusing fatty acid (FA) mixtures predialyser. Then, uraemic rats were treated with either conventional HD, Alb-based HD, lipid emulsion infusion-based HD or their combination to calculate the reduction ratio (RR), and the total solute removal (TSR) of solutes after 4 h of therapy. Results: In vitro dialysis revealed that FAs infusion prefilter increased the removal of PCS, IS, and 3-IAA 3.23-fold, 3.01-fold, and 2.24-fold, respectively, compared with baseline and increased the fractional removal of CMPF from undetectable at baseline to 14.33 ± 0.24%, with a dialysis efficacy markedly superior to Alb dialysis. In vivo dialysis showed that ω-6 soybean oil-based lipid emulsion administration resulted in higher RRs and more TSRs for PCS, IS, and 3-IAA after 4-h HD than the control, and the corresponding TSR values for PCS and IS were also significantly increased compared to that of Alb dialysis. Finally, the highest dialysis efficacy for highly bound solute removal was always observed with their combination both in vitro and in vivo. Conclusions: The concept of combined displacement- and adsorption-based dialysis may open up new avenues and possibilities in the field of dialysis to further enhance PBUTs removal in end-stage renal disease.

Artisanal mercury mining (AMM) is an informal economic activity that employs low technology and limited protection, and poses a risk to workers and their families; due to the extraction process, these scenarios involve exposure to complex mixtures of pollutants that synergistically aggravate the health of miners and people living near the site. Although mercury is the predominant pollutant, there are others such as polycyclic aromatic hydrocarbons (PAHs), toluene, arsenic, and lead which have been classified as nephrotoxic pollutants. Therefore, the purpose of this research was to evaluate the association between exposure to a complex mixture of pollutants (mercury, lead, arsenic, PAHs, and toluene) and kidney damage in artisanal Hg mining workers through early kidney damage proteins (KIM-1, OPN, RBP-4, NGAL, and Cys-C). The results demonstrate the presence of OH-PAHs at concentrations of 9.21 (6.57–80.63) μg/L, hippuric acid as a biomarker of exposure to toluene, As and Pb (655. 1 (203.8–1231) mg/L, 24.05 (1.24–42.98) g/g creatinine, and 4.74 (2.71–8.14) g/dL, respectively), and urinary Hg (503.4 (177.9–878.7) g/g creatinine) in the study population. As well as biomarkers of kidney damage, NGAL and RPB-4 were found in 100% of the samples, KIM-1 and Cys-C in 44.1%, and OPN in 41% of the miners. Significant correlations were found between several of the evaluated pollutants and early kidney damage proteins. Our results demonstrate the application of the early kidney damage biomarkers for the assessment of damage caused by the exposure to mixtures of pollutants and, therefore, the urgent need for monitoring in AMM areas.

Urinary hippuric acid (uHA) is one of the biomonitoring parameters of toxic organic exposure, such as toluene. Repeated exposure to a low concentration of toluene may lead to chronic effects such as central nervous system damage. In the preliminary study, toluene was found in the batik industry's working area in Yogyakarta, Indonesia. This study aims to assess the health condition of batik workers to toluene exposure based on the concentration of uHA. There were 52 respondents divided into 2 groups: the batik workers as the exposed group (30 respondents) and the non-batik workers as the control group (22 respondents). The urine sample was taken from batik workers at the end of the shift, and uHA was measured using spectrophotometry. The uHA value was corrected with urinary creatinine. The results showed that the average uHA concentration of batik workers was higher than that of the control group. The result also showed that workers with more than 2 years working period, writing workers, and stamping workers give an Odds Ratio (OR) of 6.43, 6.75, and 9.00 respectively on having a higher concentration of uHA. Workers with toluene exposure symptoms were also having a higher concentration of uHA than workers without any symptoms., Hippuric acid, Batik industry, Toluene exposure, Biomarker, Batik wax.

Background Prenatal and postnatal conditions are crucial for the development of calves. Primiparous cows are still maturing during pregnancy, thus competing with the nutritional needs of their offspring. Therefore, mature cows might provide a superior intrauterine condition. Furthermore, weaning calves at an older age might affect them positively as well by reducing stress and offering time for various organs and their functions to develop. We aimed to evaluate effects of mothers’ parity and calves’ weaning age on gastrointestinal development and corresponding acid–base balance. Fifty-nine female German Holstein calves (about 8 days old) were investigated in a 2 × 2 factorial experiment with factors weaning age (7 vs. 17 weeks) and parity of mother (primiparous vs. multiparous). Calves were randomly assigned to one of these four groups. Animal behavior that was observed included resting, chewing and active behavior. Results Behavioral patterns were interactively affected by time and weaning age. Rumen sounds per 2 min increased in early-weaned calves during their weaning period. In late-weaned calves a consistently increase in rumen sounds was already recorded before their weaning period. Urinary N-containing compounds (creatinine, hippuric acid, uric acid, urea, allantoin) were interactively affected by time and weaning age. Concentrations of all measured compounds except urea increased during early weaning. All except hippuric acid concentration decreased in early-weaned calves after weaning. In late-weaned calves allantoin and uric acid increased before weaning and did not change during weaning. Conclusion These results suggest that late-weaned calves developed adequate rumen functions and acid–base balance, whereas early-weaned calves might have suffered from ruminal acidosis and catabolism. Weaning calves at 7 weeks of age might be too early for an adequate rumen development.

Yoghurts from cow, goat and sheep milk were produced and stored under defined conditions to monitor the influence of various factors on the benzoic acid content as determined by Ultra High Performance Liquid Chromatography (UHPLC). The highest level of benzoic acid was found in sheep yoghurt (43.26 ± 5.11 mg kg−1) and the lowest in cow yoghurt (13.38 ± 3.56 mg kg−1), with goat yoghurt (21.31 ± 5.66 mg kg−1) falling in between. Benzoic acid content did not show statistically significant variation until the second and third weeks of storage, and the dynamics of this variation varied depending on the type of yoghurt. The yoghurt culture containing different strains of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus also affected the contents of benzoic acid. Further, the different storage temperatures (2 and 8 °C) as well as the temperatures used to milk heat treatment before yoghurt production (80, 85 and 90 °C) affected the amount of benzoic acid in different types of yoghurts.

This work presents the results of the first Serbian monitoring campaign performed to assess the occupational exposure of petrochemical industry workers to benzene (B), toluene (T), ethylbenzene (E), and xylene (X), known collectively as BTEX. The following urinary biomarkers were investigated: phenol, hippuric acid, o-Cresol, p-Cresol, and creatinine. BTEX compounds were collected in 2014 using Casella passive samplers. Multivariate statistical analysis was performed to put in evidence the correlation between the BTEX measured in air and the concentration of urinary biomarkers. While the results indicate an elevated presence of benzene in the air in the working environment studied that surpasses the national and European Occupational Exposure Limits (OEL), the levels of the remaining (TEX) parameters measured were below the OEL. The high relative standard deviations (RSD) for the concentrations of each BTEX compound (68–161 mg m−3) point toward an intensive occupational exposure to BTEX. This was confirmed by relevant urine biomarkers, particularly by the mean values of phenol, which were ten and fourteen times higher than the ones found in the control group (14–12 mg g−1 of creatinine). On average, workers are at a higher risk of developing cancer (6.1 × 10−3), with risk levels exceeding the US EPA limits. Benzene levels should therefore be maintained under tight controls and monitored via proper urinary biomarkers.

Acute Kidney Injury (AKI) affects up to 30% of the patients who undergo cardiac surgery (CVS) and is related to higher mortality. We aim to investigate molecular features associated with in-hospital AKI development and determine the predictive value of these features when analyzed preoperatively. This is a case-control study. From an initial cohort of 110 recruited subjects, a total of 60 patients undergoing cardiac surgery were included: 20 (33%) developed in-hospital AKI (CVS-AKI) and 40 did not (controls, CVS-C). Pre- and post-surgery samples were collected and a prospective study was carried out. A total of 312 serum samples and 258 urine samples were analyzed by nuclear magnetic resonance, mass spectrometry and ELISA. Six features predicted AKI development in pre-surgery samples: urinary kidney functional loss marker kidney injury molecule-1 (uKIM-1), 2-hydroxybutyric acid, 2-hydroxyphenylacetic acid, hippuric acid, phosphoethanolamine and spermidine. Two of them stood out as powerful predictors. Pre-surgery uKIM-1 levels were increased in CVS-AKI vs. CVS-C (AUC = 0.721, p-value = 0.0392) and associated strongly with the outcome (OR = 5.333, p-value = 0.0264). Spermidine showed higher concentration in CVS-AKI (p-value &lt, 0.0001, AUC = 0.970) and had a strong association with the outcome (OR = 69.75, p-value &lt, 0.0001). uKIM-1 and particularly spermidine predict in-hospital AKI associated with CVS in preoperative samples. These findings may aid in preventing postoperative AKI and improve prognosis of CVS.

Compounds that contribute to the somatosensory flavor profile of bovine fluid milk products were investigated. Sensory descriptive analysis defined five main attributes that consisted of “mouthcoating, astringent/drying, fatty texture, dairy mouthfeel, and tingling/irritation” sensations. Utilizing multi-dimensional LC sensory guided fractionation, compounds with these attributes were selected, purified and subsequently identified by LC/MS as orotic acid, pantothenic acid, hippuric acid, and p-cresol sulfate. Quantitative analysis of the four compounds across skim milk, low fat milk and whole milk indicated the concentrations were not significantly different; however, they were significantly lower in cream. Sensory recombination milk model analysis of each compound at endogenous concentrations of fluid milk indicated all compounds were sensory active. Furthermore, using a 2-AFC sensory test, skim milk spiked at two-fold higher concentrations of the 4 compounds had a significantly “creamier, fuller body” when compared with skim milk itself (α = 0.01).

Hippuric acid (HA) crystals were grown by conventional slow evaporation method and were doped with urea and thiourea. The solvent used was acetone. The obtained crystals were subjected to single crystal XRD studies using ENRAF NONIUS CAD4-F single crystal X-ray diffractometer with MoKα (λ = 0.7107 A) radiation. The Second harmonic studies reveal that the crystals have appreciable conversion efficiency. The etching studies were carried using Ethanol, methanol and acetone as etchants. The observations indicate that the deformation is minimum. The mechanical hardness were determined and it showed that the crystals are stable for device applications.

The possibility of developing a means of SBS for controlling oncological diseases in the early stages is considered. The SBS spectra of biological structures close to tumor markers are investigated experimentally in order to obtain a diagnostic option for when there are several markers in solutions of ethyl alcohol, protein citrated solution, and blood serum at the same time. Estimates of the ratio of the logarithm of methylmercaptan intensity to hippuric acid show that this technique allows us to find with high probability these elements in biological media, directly in urine and otherwise.

Inhibitors of aldose reductase provide a feasible mode of action against diabetic complications. Based on the marketed aldose reductase inhibitor epalrestat containing rhodanine nucleus, rhodanine-3-hippuric acid and its 5-arylidene derivatives were synthesized. The structure of newly synthesized compounds was confirmed by IR, 1H NMR, and 13C NMR spectrometry. In vitro aldose reductase inhibitory activity of the synthesized compounds was assayed and the results showed that most of the derivatives were potent against aldose reductase with IC50 values ranging from 0.2 to 2.36 µM. Two of the compounds with the highest efficacies among the tested compounds (IC50 values of 0.2 and 0.6 µM) were more potent than epalrestat. Molecular docking studies were undertaken to explore the binding modes of all compounds into the active site of aldose reductase in order to rationalize the inhibitory efficacy of these derivatives. Rhodanine-3-hippuric acid and all its arylidene derivatives fulfil Lipinski’s rule and show good drug-likeness property. In conclusion, novel compounds synthesized in the present study have proved to be potential drugs for diabetic complications.

In order to comprehend the binding of an important metabolite, hippuric acid, with human serum albumin and to understand its chemical and electronic nature, an experimental charge-density analysis has been carried out using high-resolution diffraction data collected under cryogenic conditions, and all the results have been compared with theoretical findings using the B3LYP/6-311++g(2d,2p) level of theory. The structure displays very strong classical hydrogen bonds as well as other noncovalent interactions, which have been fully characterized using Hirshfeld surface analysis and Bader's quantum theory of atoms in molecules. Contact analysis on the Hirshfeld surfaces shows that the O...H, C...H and C...N intermolecular interactions are enriched and gives their relative strengths. Topological analysis of the electron density shows the charge concentration/depletion of hippuric acid bonds in the crystal structure. Electrostatic parameters such as atomic charges and dipole moments were calculated. The mapping of atomic basins and the calculation of respective charges show the atomic volumes of each atom as well as their charge contributions in the hippuric acid crystal structure. The dipole-moment calculations show that the molecule is very polar in nature. Calculations of the electrostatic potential show that the chain part of the molecule has a higher concentration of negative charge than the ring, which might be instrumental in its strong binding with the polar residues of site II of human serum albumin.