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1.
Zhongguo Zhong Yao Za Zhi ; 48(2): 492-506, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725239

RESUMO

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.


Assuntos
Medicamentos de Ervas Chinesas , Glomerulonefrite , Ratos , Animais , Creatinina , Ácido Araquidônico , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Glomerulonefrite/tratamento farmacológico , Metabolômica , Biomarcadores , Proteínas Sanguíneas , Ureia
2.
Int J Mol Sci ; 24(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36675066

RESUMO

Industrial fish and aquaculture processing leads to the generation of a huge quantity of by-products, whose accumulation and mismanagement involve serious environmental consequences as well as high economic losses. Taking advantage of these residues as a source of added-value compounds must be a priority in a circular economy. This work is a preliminary study to analyze the possibility of using the eutectic mixture of urea and sodium acetate trihydrate as a solvent for collagen extraction. To that end, the solid-liquid equilibrium of the system was determined in order to define the exact composition and temperature of the eutectic. The solubility in this solvent of the main amino acids that constitute fish collagen was studied at several temperatures and atmospheric pressure. At 308.15 K, solubilities of the major constituents of the target protein, namely L-proline, trans-4-hydroxy-L-proline, and glycine, were 0.19, 0.16, and 0.12 (mass fraction), respectively. These values increased with temperature. Dilution with water (50 wt%) allowed operation at lower temperature and led to an increase in the solubilities. The van 't Hoff model was satisfactorily used to correlate the experimental data and to calculate apparent properties of dissolution. All the dissolution processes studied herein are endothermic, non-spontaneous, and enthalpy-driven. Both the eutectic and its mixture with water are promising solvents for the design of an environmentally benign process for collagen extraction.


Assuntos
Ureia , Água , Solventes/química , Água/química , Solubilidade , Acetato de Sódio , Aminoácidos
3.
Drug Des Devel Ther ; 17: 107-128, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36712944

RESUMO

Background: Cichorium intybus L. formula (CILF) is a traditional Chinese medicine (TCM) widely used in the treatment of gout and hyperuricemic nephropathy (HN). The aim of this research was to investigate the potential protective effect of CILF against HN and elucidated the underlying mechanism. Methods: CILF water extract was administered to an HN rat model established by adenine combined with ethambutol. The levels of uric acid (UA), serum urea nitrogen (UREA), and creatinine (CREA) were detected. Changes in the pathology and histology of the kidney were observed by hematoxylin-eosin staining. The 16S rRNA of the gut microbiota was sequenced. The binding ability of the main ingredients of CILF to key targets was analyzed by network pharmacology and molecular docking. The expression levels of the related mRNAs and proteins in the kidney were evaluated by RT-qPCR and immunohistochemistry analysis. Results: CILF administration significantly alleviated increases in UA, UREA, and CREA, structural damage, and kidney dysfunction. Gut microbiota analysis was applied to explore the pharmacological mechanism of the effects of CILF on bacterial diversity and microbiota structure in HN. CILF decreased the abundance of Bacteroides. In addition, it increased the abundance of Lactobacillaceae, Erysipelotrichaceae, Lachnospiraceae, Ruminococcaceae, and Bifidobacterium. Based on network pharmacology and molecular docking analysis, CILF profoundly influenced the IL17, TNF and AGE-RAGE signaling pathway. Additionally, CILF inhibited the expression of STAT3, VEGFA and SIRT1 to improve the symptoms of nephropathy. Our research suggested that CILF protects against kidney dysfunction in rats with HN induced by adenine combined with ethambutol. Conclusion: Our findings on the anti-HN effects of CILF and its mechanism of action, from the viewpoint of systems biology, and elaborated that CILF can alter the diversity and community structure of the gut microbiota in HN, providing new approaches for the prevention and treatment of HN.


Assuntos
Chicória , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Hiperuricemia , Animais , Ratos , Farmacologia em Rede , Ácido Úrico , Etambutol , Simulação de Acoplamento Molecular , RNA Ribossômico 16S , Hiperuricemia/tratamento farmacológico , Adenina , Creatinina , Ureia , Medicamentos de Ervas Chinesas/farmacologia
5.
Trop Anim Health Prod ; 55(1): 35, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624339

RESUMO

The aim of this study was to evaluate the effect of the replacement of soybean meal by increasing levels of sugarcane yeast and urea on the energy, enzymatic, protein, mineral, and hormonal profiles of buffalo heifers. Twenty Murrah heifers with an average body weight of 168 ± 2.0 kg and 1 year old were used in a completely randomized design. The treatments consisted of the replacement of soybean meal by increasing levels of sugarcane yeast and urea (0, 33, 67, and 100% dry matter). The animals were weighed at the beginning and end of the experimental period, and blood was collected on the final day. The replacement of soybean meal with sugarcane yeast influenced the performance and metabolic dynamics, with total weight gain (P = 0.005) and average daily gain (P = 0.015), presenting, for both variables, a quadratic effect. Considering the biochemical profile, there was an influence on the serum concentration of triglycerides (P = 0.055), the serum activities of aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase (P < 0.05), in addition to the serum concentration of phosphorus (P = 0.007) and potassium (P = 0.053), which showed positive linear effects. The hormonal profile was not influenced by diets (P > 0.05). The elements copper, iron, and zinc were able to be quantified at all levels of sugarcane yeast and urea in the diets offered. The use of sugarcane yeast with urea promotes adequate metabolic response of buffalo heifers and can replace up to 100% of soybean meal in the concentrate.


Assuntos
Búfalos , Saccharum , Animais , Feminino , Bovinos , Ureia , Saccharomyces cerevisiae , Farinha , Dieta/veterinária , Minerais , Grão Comestível , Ração Animal/análise , Digestão
6.
Sci Rep ; 13(1): 326, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609475

RESUMO

Nitrogen (N) and potassium (K) are essential nutrients for Italian ryegrass (Lolium multiflorum L.) growth. A 2-year field experiment with a split-plot design was conducted to study the effect of N fertilizer type combined with different K fertilizer rates on the soil mineral N and K availability, and growth characteristics of Italian ryegrass. The main plots were assigned to two N fertilizer types, controlled-release urea (CRU) and common urea. While low, moderate and high potassium chloride (KCl) rates (150, 300 and 450 kg ha-1, respectively) were assigned to the subplots. Compared with the common urea treatments, the CRU significantly increased the SPAD value, plant height, leaf area, and photosynthetic index of Italian ryegrass, which significantly prolonged the green stage of Italian ryegrass and prevented premature senescence. Moreover, the dry yields of the CRU increased by 4.5-12.5% in 2019 and 10.9-25.3% in 2020 compared with the urea, respectively. At the same time, compared with the KCl150 and KCl450 treatments, the KCl300 treatment resulted in better plant growth. Overall, the CRU × KCl300 maximized the soil inorganic N and different soil K forms, and reduced the soil N/K leaching. The root length, volume, surface area, average diameter, tips and branches were also improved, and there was a significant N × K interaction effect on the tips. The CRU combined with 300 kg ha-1 KCl fertilization enhanced crop growth by improving leaf photosynthesis, soil fertility, and yield and should be recommended as the best fertilizer ratio for Italian ryegrass production.


Assuntos
Lolium , Solo , Agricultura/métodos , Cloreto de Potássio , Preparações de Ação Retardada , Ureia/farmacologia , Fertilizantes/análise , Nitrogênio , Itália
7.
Biosensors (Basel) ; 13(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36671947

RESUMO

Circulating body fluids such as blood, urea, saliva, cerebrospinal fluid, etc [...].


Assuntos
Técnicas Biossensoriais , Líquidos Corporais , Saliva , Biomarcadores , Ureia
8.
PLoS One ; 18(1): e0278262, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36706079

RESUMO

BACKGROUND: Parkinson disease (PD) psychosis (PDP) is a disabling non-motor symptom. Pharmacologic treatment is limited to pimavanserin, quetiapine, and clozapine, which do not worsen parkinsonism. A Food and Drug Administration black box warning exists for antipsychotics, suggesting increased mortality in elderly patients with dementia. However, the reasons for higher mortality are unknown. AIM: Expanding on prior work exploring mortality in treated PDP patients, we conducted a retrospective comparison to understand the links between treatment regimen, clinical characteristics, and negative outcomes. METHODS: Electronic medical record data extraction included clinically diagnosed PD patients between 4/29/16-4/29/19 and excluded patients with primary psychiatric diagnoses or atypical parkinsonism. Mortality and clinical characteristics during the study period were compared between untreated patients and those receiving pimavanserin, quetiapine, or both agents (combination). Mortality analyses were adjusted for age, sex, levodopa equivalent daily dose (LEDD), and dementia. RESULTS: The pimavanserin group (n = 34) had lower mortality than the untreated group (n = 66) (odds ratio = 0.171, 95% confidence interval: 0.025-0.676, p = 0.026). The untreated group had similar mortality compared to the quetiapine (n = 147) and combination (n = 68) groups. All treated groups had a higher LEDD compared to the untreated group, but no other differences in demographics, hospitalizations, medical comorbidities, medications, or laboratory values were found between the untreated and treated groups. CONCLUSIONS: PDP patients receiving pimavanserin had lower mortality than untreated patients. We found no other clear differences in clinical characteristics to explain the mortality risk. Prospective randomized trials are needed to definitively identify the optimal PDP treatment regimen and associated risks.


Assuntos
Antipsicóticos , Demência , Doença de Parkinson , Transtornos Psicóticos , Humanos , Idoso , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Fumarato de Quetiapina/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Transtornos Psicóticos/tratamento farmacológico , Antipsicóticos/efeitos adversos , Ureia/farmacologia , Levodopa/uso terapêutico , Demência/tratamento farmacológico , Demência/induzido quimicamente
9.
Br Dent J ; 234(2): 120, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36707587
10.
Animal ; 17(1): 100695, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36608539

RESUMO

Various studies with growing ruminants report increases in nitrogen use efficiency (NUE) when feeding oscillating (OS) dietary CP, whereas limited research with lactating dairy cows demonstrates a lack of improvement in NUE when feeding OS diets. We hypothesised that a total mixed ration (TMR) delivering OS CP (48-h phases of 134 and 171 g CP/kg DM, respectively) compared to a static CP TMR (ST; 152 g CP/kg DM) would result in similar or increased urinary purine derivative excretion (as a marker of microbial protein synthesis (MPS)) and greater urinary nitrogen excretion in lactating dairy cows. Responses in intake, production, apparent total tract digestibility (ATTD), nutrient balance, and estimated MPS were evaluated using faecal and urine collection in 12 multiparous cows (172 ± 39 d in milk) in a randomised complete block design, where total urinary output was estimated indirectly. All measurements were taken during d 8 (at 1700) to d 16 (at 1700) of the 16-d study that followed a 28-d period in which cows already received their respective treatments. Dry matter intake, yields of milk, protein, fat, lactose, and fat- and protein-corrected milk were similar for ST and OS. Milk composition, BW, and body condition score also did not differ between treatments, except for a tendency for increased milk urea concentration with OS (13.7 vs 12.4 mg/dL). Feed efficiency, NUE and ATTD of organic matter, NDF, CP and gross energy did not differ, but ATTD of crude fat (658 vs 627 g/kg) and starch (980 vs 975 g/kg) increased, and ATTD of DM (702 vs 691 g/kg) tended to increase with OS. Milk energy as a proportion of digested energy tended to decrease with OS (34.6 vs 37.1%), but other energy metabolism variables were not affected by treatment. Estimated urinary nitrogen excretion increased (165 vs 144 g/d), estimated urinary nitrogen as a proportion of nitrogen intake tended to increase (25.3 vs 22.7%), and milk nitrogen as a proportion of digested nitrogen decreased (47.3 vs 51.8%) in response to OS. Estimated urinary excretion of creatinine (184 vs 165 mmol/d), uric acid (29 vs 20 mmol/d) and urea (3.1 vs 2.5 mol/d) increased, but other nitrogen metabolism parameters were not affected by OS. Overall, oscillating dietary CP content did not affect lactational performance, milk NUE, or estimated MPS. However, ATTD of some nutrients increased, postabsorptive energy use for milk synthesis tended to decrease, and estimated urinary nitrogen losses increased with OS.


Assuntos
Digestão , Lactação , Animais , Bovinos , Feminino , Ração Animal/análise , Dieta/veterinária , Proteínas na Dieta/metabolismo , Lactação/fisiologia , Leite/metabolismo , Nitrogênio/metabolismo , Nutrientes , Rúmen/metabolismo , Ureia/metabolismo
11.
Anal Chim Acta ; 1240: 340733, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36641152

RESUMO

In this work, pH-sensitive blue fluorescent carbon dots (CDs) with high fluorescence quantum yield (17.24%) were synthesized by hydrothermal method using Toona sinensis leaves and ethylenediamine (EDA) as raw materials. The CDs can detect urea with a limit of detection (LOD) of 6.700 mmol L-1. For more sensitive detection of urea, we constructed a ratiometric fluorescent probe (CDs@5-FAM) using CDs and 5-carboxyfluorescein (5-FAM). The CDs@5-FAM probe can rapidly and sensitively detect urea according to the changes of I514/I405, with LOD as low as 0.014 mmol L-1. Furthermore, with the help of a smartphone and RGB analysis software, urea's visual intelligent detection was realized using a CDs@5-FAM probe. The method proposed in this paper is consistent with the standard method, which indicates that the pH-sensitive ratiometric fluorescent probe CDs@5-FAM is accurate and reliable for practical application. It provides a new way for rapid and visual detection of urea.


Assuntos
Corantes Fluorescentes , Pontos Quânticos , Humanos , Carbono , Toona , Ureia
12.
World J Microbiol Biotechnol ; 39(3): 80, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36646906

RESUMO

Plant mediated synthesis of metallic nanomaterials has emerged as a non-toxic and economical approach to their applications in diverse fields especially in biomedical sciences. Herein, this study first time reporting the use of Bombax ceiba flower extract for synthesis of selenium nanoparticles (SeNPs). Initially, SeNPs were confirmed by turning the color of reaction mixtures from light yellow to brick-red. Scanning electron microscope (SEM) and Transmission electron microscopy (TEM) images showed spherical shaped nanoparticles with smooth surface, size ranges between 30 and 150 nm. Dynamic light scattering (DLS) showed 100-150 nm for the distribution of particle size. X-ray diffraction (XRD) analysis revealed SeNPs crystallinity and confirmed by matching with selenium JCPD card No. 06-362. Energy-dispersive X-ray (EDX) spectra showed presence of pure Se peaks that corroborate the conversion of selenium ions into its elemental form by bio-reduction. Fourier-transform infrared spectroscopy (FTIR) spectra demonstrated that involvement of -OH, C-H, C=C, and C=O functional groups for SeNPs formation. Raman Spectra peaks at 250 cm-1 represent asymmetric trigonal selenium (t-Se). Ultraviolet-visible spectrophotometer (UV-Vis) peaks at 296 and 306 nm which is an indication of surface plasmon resonance (SPR). Moreover, maximum antibacterial activity of SeNPs were observed against Staphylococcus aureus- a gram positive bacteria that possess zone of inhibition (ZOI) 20 mm and Klebsiella pneumonia and Pseudomonas aeruginosa-gram negative bacteria with ZOI 28 mm, respectively, at concentration 100 µg/ml. In addition, the surface functionalities induced through extract components adhere over Se binds with urea and give its detection up to 1mM in milk sample. Conclusively, synthesized SeNPs may function as a potential antibacterial pharmaceutical candidate.


Assuntos
Bombax , Nanopartículas Metálicas , Nanopartículas , Selênio , Selênio/química , Ureia , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química
13.
Biomed Pharmacother ; 158: 114170, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36587555

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel cholesterol-lowering treatment for decreasing the risk of atherosclerosis. We have previously shown that active immunization using the antiPCSK9 vaccine could decrease hypercholesterolemia and impede the development of atherosclerotic lesions in the experimental model of atherosclerosis. Here, we evaluated the toxicity of the vaccine in healthy mice. METHODS: Forty male and female albino mice were divided into 4 experimental groups, including vaccine female (10 mice) and male (10 mice) groups receiving the antiPCSK9 vaccine as well as the corresponding control female (10 mice) and male (10 mice) groups receiving the phosphate buffer. Vaccination was planned based on 4 subcutaneous injections of the vaccine formulation (10 µg/mouse) in bi-weekly intervals. The toxicity study was performed by the subacute protocol, 28 days after the last vaccine injection. To this end, the plasma levels of lipid indexes, urea, creatinine, AST, ALT, ALP, and fasting plasma glucose (FPG), as well as the CBC test were measured. To evaluate histopathological alterations, various tissues including the heart, liver, kidney, spleen, and brain were studied using hematoxylin & eosin (H&E) staining by an expert pathologist. The severity of damage to the tissue was considered based on the standard classification; grade 1 as light damage, grade 2 as moderate damage, grade 3 as near intense damage, and grade 4 as intense damage. RESULTS: The results showed non-significant changes of total cholesterol, LDL-C, triglyceride, HDL-C, FBS, creatinine, urea, AST, ALP, ALT, and PAB in the vaccinated mice when compared with control mice. The CBS test indicated that there were no significant changes in the levels of WBC, RBC, HGB, HCT, MCH, MCHC, PLT, LYM, NEUT, MCV, RDW-S, PDW, and MPV in the vaccinated mice when compared with control mice. Evaluating histopathological alterations in various tissues indicated no significant adverse effects in vaccinated mice when compared to control mice. CONCLUSION: The findings of the present study indicate that antiPCSK9 is safe and exerts no adverse effects on the function of different organs and blood levels of cellular and biochemical biomarkers in healthy mice.


Assuntos
Aterosclerose , Pró-Proteína Convertase 9 , Vacinas de Subunidades , Animais , Feminino , Masculino , Camundongos , Aterosclerose/prevenção & controle , Creatinina , Peptídeos , Ureia
14.
Protein Sci ; 32(1): e4533, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36482045

RESUMO

Amide-π interactions, in which an amide interacts with an aromatic group, are ubiquitous in biology, yet remain understudied relative to other noncovalent interactions. Recently, we demonstrated that an electrostatically tunable amide-π interaction is key to recognition of histone acyllysine by the AF9 YEATS domain, a reader protein which has emerged as a therapeutic target due to its dysregulation in cancer. Amide isosteres are commonly employed in drug discovery, often to prevent degradation by proteases, and have proven valuable in achieving selectivity when targeting epigenetic proteins. However, like amide-π interactions, interactions of amide isosteres with aromatic rings have not been thoroughly studied despite widespread use. Herein, we evaluate the recognition of a series of amide isosteres by the AF9 YEATS domain using genetic code expansion to evaluate the amide isostere-π interaction. We show that compared to the amide-π interaction with the native ligand, each isostere exhibits similar electrostatic tunability with an aromatic residue in the binding pocket, demonstrating that the isosteres maintain similar interactions with the aromatic residue. We identify a urea-containing ligand that binds with enhanced affinity for the AF9 YEATS domain, offering a promising starting point for inhibitor development. Furthermore, we demonstrate that carbamate and urea isosteres of crotonyllysine are resistant to enzymatic removal by SIRT1, a protein that cleaves acyl post-translational modifications, further indicating the potential of amide isosteres in YEATS domain inhibitor development. These results also provide experimental precedent for interactions of these common drug discovery moieties with aromatic rings that can inform computational methods.


Assuntos
Amidas , Histonas , Ligantes , Histonas/metabolismo , Domínios Proteicos , Ureia
15.
Eur J Pharmacol ; 939: 175470, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36543287

RESUMO

Mitochondria in tumor cells are functionally different from those in normal cells and could be targeted to develop new anticancer agents. We showed recently that the aryl-ureido fatty acid CTU is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells by increasing the production of reactive oxygen species (ROS), activating endoplasmic reticulum (ER)-stress and promoting apoptosis. However, prolonged treatment with high doses of CTU were required for in vivo anti-tumor activity. Thus, new strategies are now required to produce agents that have enhanced anticancer activity over CTU. In the present study we prepared a novel aryl-urea termed 3-thiaCTU, that contained an in-chain sulfur heteroatom, for evaluation in tumor cell lines and in mice carrying tumor xenografts. The principal finding to emerge was that 3-thiaCTU was several-fold more active than CTU in the activation of aryl-urea mechanisms that promoted cancer cell killing. Thus, in in vitro studies 3-thiaCTU disrupted the mitochondrial membrane potential, increased ROS production, activated ER-stress and promoted tumor cell apoptosis more effectively than CTU. 3-ThiaCTU was also significantly more active than CTUin vivo in mice that carried MDA-MB-231 cell xenografts. Compared to CTU, 3-thiaCTU prevented tumor growth more effectively and at much lower doses. These findings indicate that, in comparison to CTU, 3-thiaCTU is an aryl-urea with markedly enhanced activity that could now be suitable for development as a novel anticancer agent.


Assuntos
Antineoplásicos , Ácidos Graxos , Humanos , Animais , Camundongos , Ácidos Graxos/farmacologia , Ácidos Graxos/metabolismo , Ureia/farmacologia , Ureia/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático , Potencial da Membrana Mitocondrial
16.
Magn Reson Med ; 89(2): 774-786, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36226662

RESUMO

PURPOSE: Standardized blood tests often lack adequate sensitivity and specificity to capture the gradual progression of renal injuries. We suggest a multiparametric molecular MRI approach as a noninvasive tool for monitoring renal function loss and distinguishing different types of renal injuries. METHODS: CEST and quantitative magnetization transfer (qMT) imaging were performed on cisplatin (n = 16) and aristolochic acid (AA)-induced nephropathy (n = 22) mouse models at 7T with an infusion of either saline or urea. Seven-pool Lorentzian fitting was applied for the analysis of CEST Z-spectra, and the T1 -corrected CEST contrast apparent exchange-dependent relaxation (AREX) from urea (+1 ppm) and two nuclear Overhauser enhancement (NOE) pools (-1.6 and -3.5 ppm) were measured. Similarly, qMT spectra were fitted into two-pool Ramani equation and the relative semi-solid macromolecular pool-size ratio was measured. Histology of mouse kidneys was performed to validate the MR findings. RESULTS: AA model showed disrupted spatial gradients of urea in the kidney and significantly decreased NOE CEST and qMT contrast. The cisplatin model showed slightly decreased qMT contrast only. The orrelation of MR parameters to histological features showed that NOE CEST and qMT imaging are sensitive to both acute and chronic injuries, whereas urea CEST shows a significant correlation only to acute injuries. CONCLUSION: These results indicate that our multiparametric approach allows comprehensive and totally noninvasive monitoring of renal function and histological changes for distinguishing different nephropathies.


Assuntos
Cisplatino , Ureia , Animais , Camundongos , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Rim/diagnóstico por imagem
17.
Environ Res ; 216(Pt 3): 114639, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36309217

RESUMO

Clinical laboratory in hospital can produce amounts of health data every day. The purpose of this study was to mine biomarkers from clinical laboratory big data associated with the air pollution health risk assessment using clinical records. 13, 045, 629 clinical records of all 27 routine laboratory tests in Changsha Central Hospital, including ALB, TBIL, ALT, DBIL, AST, TP, UREA, UA, CREA, GLU, CK, CKMB, LDL-C, TG, TC, HDL-C, CRP, WBC, Na, K, Ca, Cl, APTT, PT, FIB, TT, RBC and those daily air pollutants concentration monitoring data of Changsha, including PM2.5, PM10, SO2, NO2, CO, and O3 from 2014 to 2016, were retrieved. The moving average method was used to the biological reference interval was established. The tests results were converted into daily abnormal rate. After data cleaning, GAM statistical model construction and data analysis, a concentration-response relationship between air pollutants and daily abnormal rate of routine laboratory tests was observed. Our study found that PM2.5 had a stable association with TP (lag07), ALB (lag07), ALT (lag07), AST (lag07), TBIL (lag07), DBIL (lag07), UREA (lag07), CREA (lag07), UA (lag07), CK (lag 06), GLU (lag07), WBC (lag07), Cl (lag07) and Ca (lag07), (P < 0.05); O3 had a stable association with AST (lag01), CKMB (lag06), TG (lag07), TC (lag05), HDL-C (lag07), K (lag05) and RBC (lag07) (P < 0.05); CO had a stable association with UREA (lag07), Na (lag7) and PT (lag07) (P < 0.05); SO2 had a stable association with TP (lag07) and LDL-C (lag0) (P < 0.05); NO2 had a stable association with APTT (lag7) (P < 0.05). These results showed that different air pollutants affected different routine laboratory tests and presented different pedigrees. Therefore, biomarkers mined from routine laboratory tests may potentially be used to low-cost assess the health risks associated with air pollutants.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Dióxido de Nitrogênio/análise , LDL-Colesterol , Poluição do Ar/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Medição de Risco , Biomarcadores/análise , Material Particulado/análise , Ureia/análise , China
18.
Sci Total Environ ; 858(Pt 3): 160170, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379335

RESUMO

The sluggish kinetics of oxygen evolution reaction (OER) is the bottleneck of alkaline water electrolysis. The urea oxidation reaction (UOR) with much faster kinetics was to replace OER. To further promote UOR, a heterojunction structure assembled of CoSx and MoOx was established, and then its superior catalytic activity was predicted by DFT calculation. After that, an ultra-thin CoSx-MoOx@nickel foam (CoSx-MoOx@NF) electrode with a Mott-Schottky structure was prepared via a facile hydrothermal method, followed by a low-temperature vulcanization. Results highlighted CoSx-MoOx@NF electrode presented a superior performance toward UOR, OER, and H2 evolution reaction (HER). Notably, it exhibited excellent electrocatalytic performance for OER (1.32 V vs. RHE, 10 mA cm-2), UOR (1.305 V vs. RHE, 10 mA cm-2), and urea-assisted overall water splitting with a low voltage (1.38 V, 10 mA cm-2) when CoSx-MoOx@NF electrode served as both anode and cathode. It is promising to use CoSx-MoOx@NF in an electrochemical system integrated with H2 generation and urea-rich wastewater purification.


Assuntos
Eletrólise , Ureia , Eletrodos , Oxigênio , Água
19.
J Org Chem ; 88(1): 285-299, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36480555

RESUMO

The introduction of urea or thiourea functionality to the macrocycle skeleton represents an alternative way to control conformational dynamics of chiral, polyamines of a figure-shaped periodical structure. Formally highly symmetrical, these macrocycles may adapt diverse conformations, depending on the nature of an amide linker and on a substitution pattern within the aromatic units. The type of heteroatom X in the N-C(═X)-N units present in each vertex of the macrocycle core constitutes the main factor determining the chiroptical properties. In contrast to the urea-containing derivatives, the electronic circular dichroism of thioureas is controlled by the chiral neighborhood closest to the chromophore. The dynamically induced exciton couplet is observed when the biphenyl chromophores are present in the macrocycle core. In the solid state, the seemingly disordered molecules may create ordered networks stabilized by intermolecular S···halogen, H···halogen, and S···H interactions. The presence of two bromine substituents in each aromatic unit in thiourea-derived trianglamine gives rise to a self-sorting phenomenon in the crystal. In solution, this particular macrocycle exists as a dynamic equimolar mixture of two conformational diastereoisomers, differing in the spatial (clockwise and counter clockwise) arrangement of the C-Br bonds. In the crystal lattice, macrocycles of a given handedness assemble into homohelical layers.


Assuntos
Tioureia , Ureia , Estrutura Molecular , Conformação Molecular , Poliaminas
20.
Int J Pharm ; 631: 122528, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36563799

RESUMO

Dental caries is one of the most widespread chronic infectious diseases in the world. It is mainly caused by the production of acid in the biofilm from the bacterial metabolism of carbohydrates. Nowadays, the prevention of caries is mainly based on the use of topical formulations containing fluoride. However, effective fluoride supplementation may not be sufficient in high-risk individuals, leading to the exploration of alternative strategies such as the neutralization of acid in the oral cavity. Urea is hydrolyzed into ammonia by oral bacteria, leading to a local alkalization that may counteract tooth decay. Herein, we report the fabrication of 3D printed personalized dental trays with a local and prolonged release of urea. Composite filaments with tunable urea release kinetics were produced by hot melt extrusion of poly(ε-caprolactone) and poly(vinyl alcohol) or poly(ethylene glycol) blends mixed with urea. The filaments were further used to 3D print by fused deposition modeling objects capable of releasing urea in a sustained and spatially controlled manner. In vitro studies performed in the presence of Streptococcus salivarius demonstrated the ability of urea released from a 3D printed model toothguards to reduce the pH drop induced by carbohydrates. This study showed the potential of urea-loaded devices to reduce cariogenic acidification of the environment surrounding the enamel by delivering urea directly to the tooth surface.


Assuntos
Cárie Dentária , Ureia , Humanos , Liberação Controlada de Fármacos , Fluoretos , Cárie Dentária/prevenção & controle , Impressão Tridimensional , Carboidratos , Tecnologia Farmacêutica , Comprimidos
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