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1.
Environ Geochem Health ; 46(5): 172, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592578

RESUMO

Advancement in bioinspired alloy nanomaterials has a crucial impact on fuel cell applications. Here, we report the synthesis of PtPd alloy nanoclusters via the hydrothermal method using Piper longum extract, representing a novel and environmentally friendly approach. Physicochemical characteristics of the synthesized nanoclusters were investigated using various instrumentation techniques, including X-ray photoelectron spectroscopy, X-ray diffraction, and High-Resolution Transmission electron microscopy. The electrocatalytic activity of the biogenic PtPd nanoclusters towards the oxidation of formic acid and methanol was evaluated chronoamperometry and cyclic voltammetry studies. The surface area of the electrocatalyst was determined to be 36.6 m2g-1 by Electrochemical Surface Area (ECSA) analysis. The biologically inspired PtPd alloy nanoclusters exhibited significantly higher electrocatalytic activity compared to commercial Pt/C, with specific current responses of 0.24 mA cm - 2 and 0.17 mA cm - 2 at synthesis temperatures of 180 °C and 200 °C, respectively, representing approximately four times higher oxidation current after 120 min. This innovative synthesis approach offers a promising pathway for the development of PtPd alloy nanoclusters with enhanced electrocatalytic activity, thereby advancing fuel cell technology towards a sustainable energy solution.


Assuntos
Formiatos , Metanol , Piper , Ligas , Extratos Vegetais
2.
Biotechnol J ; 19(2): e2300495, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38403407

RESUMO

The optimization of bioprocess for CHO cell culture involves careful consideration of factors such as nutrient consumption, metabolic byproduct accumulation, cell growth, and monoclonal antibody (mAb) production. Valuable insights can be obtained by understanding cellular physiology to ensure robust and efficient bioprocess. This study aims to improve our understanding of the CHO-K1 cell metabolism using 1 H NMR-based metabolomics. Initially, the variations in culture performance and metabolic profiles under varied aeration conditions and copper supplementations were thoroughly examined. Furthermore, a comprehensive metabolic pathway analysis was performed to assess the impact of these conditions on the implicated pathways. The results revealed substantial alterations in the pyruvate metabolism, histidine metabolism, as well as phenylalanine, tyrosine and tryptophan biosynthesis, which were especially evident in cultures subjected to copper deficiency conditions. Conclusively, significant metabolites governing cell growth and mAb titer were identified through orthogonal partial least square-discriminant analysis (OPLS-DA). Metabolites, including glycerol, alanine, formate, glutamate, phenylalanine, and valine, exhibited strong associations with distinct cell growth phases. Additionally, glycerol, acetate, lactate, formate, glycine, histidine, and aspartate emerged as metabolites influencing cell productivity. This study demonstrates the potential of employing 1 H NMR-based metabolomics technology in bioprocess research. It provides valuable guidance for feed medium development, feeding strategy design, bioprocess parameter adjustments, and ultimately the enhancement of cell proliferation and mAb yield.


Assuntos
Cobre , Histidina , Cricetinae , Animais , Glicerol , Metabolômica/métodos , Cricetulus , Fenilalanina , Formiatos , Suplementos Nutricionais
3.
Biomed Chromatogr ; 38(3): e5803, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38098275

RESUMO

In this present study, we developed a reliable and simple ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin and isomaltopaeoniflorin in beagle dog plasma. We also analyzed the pharmacokinetics of those components after oral administration of fried Radix Paeoniae Alba (FRPA) in beagle dogs. Plasma samples were processed by protein precipitation with methanol. Chromatographic separation was performed with a Waters HSS-T3 C18 column (100 × 2.1 mm, 1.8 µm, kept at 40°C) using multiple reaction monitoring mode. A gradient elution procedure was used with solvent A (0.02% formic acid-water) and solvent B (0.02% formic acid-acetonitrile) as mobile phases. Method validation was performed as US Food and Drug Administration guidelines, and the results met the acceptance criteria. The method we establish in this experiment was successfully applied to the pharmacokinetic study after oral administration of FRPA extract to beagle dogs.


Assuntos
Medicamentos de Ervas Chinesas , Formiatos , Espectrometria de Massas em Tandem , Cães , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacocinética , Solventes
4.
Cancer Discov ; 13(12): 2566-2583, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-37728660

RESUMO

The tumor microenvironment (TME) restricts antitumor CD8+ T-cell function and immunotherapy responses. Cancer cells compromise the metabolic fitness of CD8+ T cells within the TME, but the mechanisms are largely unknown. Here we demonstrate that one-carbon (1C) metabolism is enhanced in T cells in an antigen-specific manner. Therapeutic supplementation of 1C metabolism using formate enhances CD8+ T-cell fitness and antitumor efficacy of PD-1 blockade in B16-OVA tumors. Formate supplementation drives transcriptional alterations in CD8+ T-cell metabolism and increases gene signatures for cellular proliferation and activation. Combined formate and anti-PD-1 therapy increases tumor-infiltrating CD8+ T cells, which are essential for enhanced tumor control. Our data demonstrate that formate provides metabolic support to CD8+ T cells reinvigorated by anti-PD-1 to overcome a metabolic vulnerability in 1C metabolism in the TME to further improve T-cell function. SIGNIFICANCE: This study identifies that deficiencies in 1C metabolism limit the efficacy of PD-1 blockade in B16-OVA tumors. Supplementing 1C metabolism with formate during anti-PD-1 therapy enhances CD8+ T-cell fitness in the TME and CD8+ T-cell-mediated tumor clearance. These findings demonstrate that formate supplementation can enhance exhausted CD8+ T-cell function. See related commentary by Lin et al., p. 2507. This article is featured in Selected Articles from This Issue, p. 2489.


Assuntos
Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Neoplasias/genética , Formiatos , Suplementos Nutricionais , Microambiente Tumoral
5.
Phytochem Anal ; 34(8): 938-949, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37483127

RESUMO

INTRODUCTION: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo. OBJECTIVE: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents. MATERIALS AND METHODS: A C18 column (3 × 100 mm, 2.6 µm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified. RESULTS: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues. CONCLUSION: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo.


Assuntos
Medicamentos de Ervas Chinesas , Ratos , Animais , Cromatografia Líquida de Alta Pressão , Formiatos , Espectrometria de Massas em Tandem
6.
Molecules ; 28(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37513391

RESUMO

Direct biocatalytic processes for CO2 capture and transformation in value-added chemicals may be considered a useful tool for reducing the concentration of this greenhouse gas in the atmosphere. Among the other enzymes, carbonic anhydrase (CA) and formate dehydrogenase (FDH) are two key biocatalysts suitable for this challenge, facilitating the uptake of carbon dioxide from the atmosphere in complementary ways. Carbonic anhydrases accelerate CO2 uptake by promoting its solubility in water in the form of hydrogen carbonate as the first step in converting the gas into a species widely used in carbon capture storage and its utilization processes (CCSU), particularly in carbonation and mineralization methods. On the other hand, formate dehydrogenases represent the biocatalytic machinery evolved by certain organisms to convert CO2 into enriched, reduced, and easily transportable hydrogen species, such as formic acid, via enzymatic cascade systems that obtain energy from chemical species, electrochemical sources, or light. Formic acid is the basis for fixing C1-carbon species to other, more reduced molecules. In this review, the state-of-the-art of both methods of CO2 uptake is assessed, highlighting the biotechnological approaches that have been developed using both enzymes.


Assuntos
Dióxido de Carbono , Anidrases Carbônicas , Dióxido de Carbono/química , Biocatálise , Biotecnologia , Formiatos , Formiato Desidrogenases/metabolismo , Anidrases Carbônicas/química
7.
Fish Physiol Biochem ; 49(1): 19-37, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36759400

RESUMO

Organic acids and their derivatives have been attributed to growth and well-being improvement in fish when supplemented in their diets. Therefore, this study was conducted to evaluate the ameliorative role of potassium formate (PF) in rohu Labeo rohita fingerlings. A total of 240 healthy rohu fingerlings (9.0 ± 0.5 g ± SE) were randomly divided into four equal groups in triplicates. Fish were fed with isonitrogenous feeds: PF10 (10 g PF/kg), PF20 (20 g PF/kg) and PF30 (30 g PF/kg). Feed without PF supplementation served as control. The results indicated that the specific growth rate (SGR) and feed conversion ratio (FCR) were significantly (p<0.05) higher in PF10. Total serum globulin content was found significantly (p<0.05) elevated in PF10 after the bacterial challenge. Non-specific lysozyme activity was significantly higher (p<0.05) after the challenge. The digestive protease enzyme activity was significantly (p<0.05) improved in PF10 treatment. Additionally, the digestive morphology of the treated fish was seen to be improved. Greater villus area, increased villus number, reduced lumen space in the hindgut, reduced vacuolation in mucosal folds and proliferation of goblet cells-like changes were observed in the PF-supplemented fish. Significantly (p<0.05), a higher relative percentage of survival (RPS) was observed in PF10 and PF20 treatments. The study revealed that the dietary supplementation of rohu fingerlings with lower levels of potassium formate could enhance the nutritional efficiency and physiological activities of rohu fingerlings. This study serves as a baseline for future research on the application of formic acid derivatives and other acidifiers in carp culture.


Assuntos
Cyprinidae , Potássio na Dieta , Animais , Dieta/veterinária , Suplementos Nutricionais , Formiatos/farmacologia , Proteínas , Ração Animal/análise
8.
Chem Biodivers ; 19(10): e202200536, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36099157

RESUMO

Acknowledging the importance of medicinal compounds, flavonoids, and phenolic acids in plants and human health; understanding the best time to harvest plants to get the most potentially therapeutic biological activity; and predicting and controlling the quality of medicinal plants are very useful. The rich chemical composition of medicinal lavender, as well as its antioxidant activity, has led to its wide application in the pharmaceutical, cosmetic, and food industries. In the current research, seasonal differences in phenolic content; the main constituents of essential oil, essential oil yield, and antioxidant activity; and flavonoid content were evaluated. In this investigation, for all the investigated factors, three replications were considered as completely randomized designs. The predominant natural components were α-pinene, camphene, 1,8-cineole, limonene, camphor, borneol, cryptone, isobornyl formate, cumin aldehyde, carvone, caryophyllene oxide, and epi-α-cadinol. The highest rate of 1,8-cineole was seen in summer, while camphor and borneol showed their highest percentages in the cold season. Some of the compounds such as caryophyllene oxide, isobornyl formate, and cumin aldehyde showed their highest amounts in the spring with the activation of some important plant enzymes such as peroxidase. The total content of flavonoids and some phenolic compounds (coumarin and p-coumaric acid) increased when plants received sunlight for a longer time than in the colder to warmer seasons. On the other hand, increases in chlorogenic acid and vanillin were observed in spring. Also, the highest antioxidant activity was observed in lavender, which was accompanied by an increase in the important phenolic composition of rosmarinic acid in the cold season. Generally, this investigation provides beneficial evidence about the most appropriate harvest time for lavender to produce the most favorable constituents for optimization in food, pharmaceutical, and herbal products.


Assuntos
Lavandula , Óleos Voláteis , Plantas Medicinais , Humanos , Lavandula/química , Antioxidantes/farmacologia , Antioxidantes/química , Eucaliptol , Cânfora , Limoneno , Ácido Clorogênico , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Compostos Fitoquímicos/farmacologia , Fenóis , Flavonoides , Cumarínicos , Formiatos , Aldeídos , Peroxidases , Preparações Farmacêuticas , Componentes Aéreos da Planta
9.
Zhongguo Zhong Yao Za Zhi ; 47(18): 4938-4949, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36164903

RESUMO

Qijiao Shengbai Capsules(QJ) are a common Miao medicine serving as an adjuvant cancer therapy in clinical practice.QJ consists of seven medicinal materials such as Astragalus membranaceus and Lespedeza buergeri.Its chemical components have not been clarified and the quality control needs to be improved.In this study, LC-IT-TOF-MS was used to comprehensively collect MS~1 and MS~2 fragment information of QJ and rapidly identify the chemical compositions.The chromatographic separation was performed on the Capcell core ADME column(2.1 mm×150 mm, 2.7 µm) with 0.1% formic acid aqueous solution(A) and acetonitrile(B) as mobile phases for gradient elution.High-resolution mass spectrometric information was obtained by scanning in the positive and negative ion ESI modes.A total of 107 compounds were structurally identified according to the deduced MS fragmentation patterns and comparison with standards and data reported in the literature, including 54 flavonoids, 16 phthalides, 13 alkaloids, 12 phenolic acids, 7 saponins, 2 coumarins, 2 condensed tannins, and 1 purine.This study clarified the chemical composition of QJ and provided references for the improvement of its quality standards and the elucidation of its medicinal substances.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Proantocianidinas , Saponinas , Acetonitrilas , Cápsulas , Cromatografia Líquida de Alta Pressão , Cumarínicos/análise , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Formiatos , Proantocianidinas/análise , Purinas , Espectrometria de Massas em Tandem
10.
Zhongguo Zhong Yao Za Zhi ; 47(18): 5052-5063, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36164915

RESUMO

Dangefentong Capsules is a new traditional Chinese medicine preparation for the treatment of diabetic peripheral neuropathy. It is based on the Salviae Miltiorrhizae Radix et Rhizoma-Puerariae Lobatae Radix herb pair with salvianolic acids, tanshinones and pueraria flavonoids as main components. Studying the chemical composition in vivo of Dangefentong Capsules and its metabolites is of great significance for making clear its pharmacodynamic material basis and the action mechanism. The UHPLC-Q/Orbitrap-MS/MS was applied to rapidly analyze the metabolites and metabolic pathways of Dangefentong Capsules in Beagle dogs after gavage. Eclipse plus C_(18) column(2.1 mm×50 mm, 1.8 µm) was used, and gradient elution was performed with 0.1% formic acid aqueous solution(A)-formic acid acetonitrile solution(B). A heated electrospray ion source(HESI) was employed. The scanning mode was set as the positive and negative ion mode, and the mass scanning range was m/z 100-1 000. The plasma, urine and feces samples were collected after male Beagle dogs were administered with Dangefentong Capsules. The prototype components and metabolites were identified by UHPLC-Q/Orbitrap-MS/MS analysis combined with reference substances and references. The results showed that 107 chemical components were identified, including 58 prototype components and 49 metabolites. The identified prototype components included 42 components from Salviae Miltiorrhizae Radix et Rhizoma and 16 components from Puerariae Lobatae Radix. The metabolites consist of 21 and 28 metabolites of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix, respectively. They are mainly derived from the methylation, hydroxylation, sulfation and glucuronidation of salvianolic acids, tanshinones and pueraria flavonoids. This research rapi-dly analyzes the chemical components in vivo of Beagle dogs administered with Dangefentong Capsules, laying a basis for illustrating the pharmacodynamic material basis and mechanism of Dangefentong Capsules.


Assuntos
Medicamentos de Ervas Chinesas , Pueraria , Abietanos , Acetonitrilas , Alcenos , Animais , Cápsulas , Cromatografia Líquida de Alta Pressão/métodos , Cães , Medicamentos de Ervas Chinesas/química , Flavonoides , Formiatos , Masculino , Polifenóis , Espectrometria de Massas em Tandem
11.
J Chromatogr A ; 1681: 463490, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36103747

RESUMO

The determination of secondary volatile degradation products in drying oil extracts is substantial to prevent formation of undesirable metal formates in paintings and/or other artefacts. This study develops a simple, cost-effective, and reliable, high-performance liquid chromatography with diode array detector (HPLC-DAD) method to determine three secondary volatile degradation products (methanol, formaldehyde, and formic acid) in drying oils, including linseed, poppy-seed, and walnut oil. Extraction of analytes was performed using QuEChERS-based procedure followed by metal oxide-based dispersive solid-phase extraction (d-SPE) clean-up and presented a good performance for all of the volatile analytes of interest with recoveries in the range of 90-120% after application of the nanostructured cerium oxide-based (CeO2) and zirconia-based (ZrO2) sorbents prepared by favorable and ecological-friendly methods. With a new clean-up solution for samples with high-fat content, it was possible to achieve higher recoveries than with commercial Z-Sep/C18 sorbent. In all cases, relative standard deviations (RSD) of less than 10% were achieved. No significant matrix interference was observed due to the application of effective sorbents in nanostructured form. The developed method was applied to samples of drying oils, and it was found that after storage for three months, all methanol was most likely oxidized to formaldehyde and formic acid. The concentrations of formaldehyde were in the range of 260 - 304 µg∙g-1, while formic acid concentrations ranged between 72 - 386 µg∙g-1. The highest concentration of formaldehyde (304 µg∙g-1) and formic acid (386 µg∙g-1) was found in linseed oil.


Assuntos
Óleo de Semente do Linho , Metanol , Cromatografia Líquida de Alta Pressão/métodos , Formaldeído , Formiatos , Óleos , Óxidos , Extração em Fase Sólida/métodos
12.
J Biotechnol ; 358: 67-75, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36087783

RESUMO

As a valuable platform chemical, 2,3-Butanediol (2,3-BDO) has a variety of industrial applications, and its microbial production is particularly attractive as an alternative to petroleum-based production. In this study, the regulation of intracellular carbon flux and NADH/NAD+ was used to increase the 2,3-BDO production of Enterobacter aerogenes. The genes encoding lactate dehydrogenase (ldh) and pyruvate formate lyase (pfl) were disrupted using the λ-Red recombination method and CRISPR-Cas9 to reduce the production of several byproducts and the consumption of NADH. Knockout of ldh or pfl increased intracellular NADH/NAD+ by 111 % and 113 %, respectively. Moreover, two important genes in the 2,3-BDO biosynthesis pathway, acetolactate synthase (budB) and acetoin reductase (budC), were overexpressed in E. aerogenes to further amply the metabolic flux toward 2,3-BDO production. And the overexpression of budB or budC increased intracellular NADH/NAD+ by 46 % and 57 %, respectively. In shake-flask cultivation with sucrose as carbon source, the 2,3-BDO titer of the IAM1183-LPBC was 3.55 times that of the wild type. In the 5-L fermenter, the maximal 2,3-BDO production produced by the IAM1183-LPBC was 2.88 times that of the original strain. This work offers new ideas for promoting the biosynthesis of 2,3-BDO for industrial applications.


Assuntos
Acetolactato Sintase , Enterobacter aerogenes , Liases , Petróleo , Acetolactato Sintase/metabolismo , Butileno Glicóis/metabolismo , Carbono/metabolismo , Ciclo do Carbono , Enterobacter aerogenes/genética , Enterobacter aerogenes/metabolismo , Fermentação , Formiatos , L-Lactato Desidrogenase/genética , Engenharia Metabólica/métodos , NAD/metabolismo , Piruvatos , Sacarose
13.
BMC Vet Res ; 18(1): 318, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978339

RESUMO

BACKGROUND: Good quality colostrum is characterized by high immunoglobulin concentration and low pathogen load. Some methods of pathogen reduction can decrease immunoglobulin concentration and potentially affect their function. Objectives were to determine the effect of formic acid treatment on colostral bacterial and immunoglobulin (IgG) levels before feeding, and serum immunoglobulin concentration and neutralizing capabilities after feeding. Fifteen female Holstein calf pairs born < 12 h apart from different dams were randomly assigned to receive four liters of either untreated pooled (both dams) colostrum (MC) or colostrum acidified to pH 4.0-4.5 (AC). Colostrum characteristics estimated; pH, bacterial load, IgG concentration, and neutralization of Infectious Bovine Rhinotracheitis (IBRV/BoHV-1), Bovine Viral Diarrhea (BVDV) Types 1 and 2. Blood samples were collected on days 1, 3 and monthly for 6 months and were analyzed for IgG, and both viral plus leptospiral neutralization, and total protein (day 3 only). RESULTS: Compared to MC (mean 6.7, SD 0.4; median 6.8, range 6.0-7.3), AC pH was significantly reduced (mean 4.3, SD 0.2; median 4.3, range 4.0-4.5; P < 0.001). Total coliform count (cfu/mL) was also reduced (MC mean 149, SD 444; median 1, range 0-1,700; AC mean 8, SD 31; median 0, range 0-120; P = 0.02). Colostrum IgG concentration was not significantly different between MC (mean 93.3, SD 39.7; median 92.8, range 36.7-164.4 g/L) and AC (mean 101.9, SD 36.7; median 108.3, range 33.8-164.4 g/L; P = 0.54). In calves, serum IgG peaked on day 3 (MC mean 26.1, SD 34.9; median 169.2, range 8.3-151.0 g/L; AC mean 30.2, SD 48.7; median 188.8, range 3.1-204.4 g/L; P = 0.77), and apparent efficiency of IgG absorption was not different between groups (MC mean 24.3, SD 11.4, median 25.3, range 8.6-51.3%; AC mean 22.6, SD 21.7, median 21.6, range 4.1-58.9%; P = 0.65). Thereafter, IgG levels declined but did not differ between groups. MC and AC serum neutralizing titers for IBRV, BVDV Types 1 and 2, or Leptospira interrogans serovars Canicola, and Pomona and L. borgpetersenii serovar Hardjo were not different. CONCLUSIONS: Colostrum acidification significantly decreased bacterial load fed to newborn calves without affecting colostral IgG concentration or virus neutralization. In addition, acid treatment did not affect serum IgG concentration in calves or its activity against common pathogens.


Assuntos
Colostro , Imunoglobulina G , Animais , Animais Recém-Nascidos , Bovinos , Colostro/química , Feminino , Formiatos/análise , Gravidez
14.
Cell Mol Life Sci ; 79(7): 375, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35727412

RESUMO

The SLC25A32 dysfunction is associated with neural tube defects (NTDs) and exercise intolerance, but very little is known about disease-specific mechanisms due to a paucity of animal models. Here, we generated homozygous (Slc25a32Y174C/Y174C and Slc25a32K235R/K235R) and compound heterozygous (Slc25a32Y174C/K235R) knock-in mice by mimicking the missense mutations identified from our patient. A homozygous knock-out (Slc25a32-/-) mouse was also generated. The Slc25a32K235R/K235R and Slc25a32Y174C/K235R mice presented with mild motor impairment and recapitulated the biochemical disturbances of the patient. While Slc25a32-/- mice die in utero with NTDs. None of the Slc25a32 mutations hindered the mitochondrial uptake of folate. Instead, the mitochondrial uptake of flavin adenine dinucleotide (FAD) was specifically blocked by Slc25a32Y174C/K235R, Slc25a32K235R/K235R, and Slc25a32-/- mutations. A positive correlation between SLC25A32 dysfunction and flavoenzyme deficiency was observed. Besides the flavoenzymes involved in fatty acid ß-oxidation and amino acid metabolism being impaired, Slc25a32-/- embryos also had a subunit of glycine cleavage system-dihydrolipoamide dehydrogenase damaged, resulting in glycine accumulation and glycine derived-formate reduction, which further disturbed folate-mediated one-carbon metabolism, leading to 5-methyltetrahydrofolate shortage and other folate intermediates accumulation. Maternal formate supplementation increased the 5-methyltetrahydrofolate levels and ameliorated the NTDs in Slc25a32-/- embryos. The Slc25a32K235R/K235R and Slc25a32Y174C/K235R mice had no glycine accumulation, but had another formate donor-dimethylglycine accumulated and formate deficiency. Meanwhile, they suffered from the absence of all folate intermediates in mitochondria. Formate supplementation increased the folate amounts, but this effect was not restricted to the Slc25a32 mutant mice only. In summary, we established novel animal models, which enabled us to understand the function of SLC25A32 better and to elucidate the role of SLC25A32 dysfunction in human disease development and progression.


Assuntos
Ácido Fólico , Defeitos do Tubo Neural , Animais , Humanos , Camundongos , Carbono/metabolismo , Flavina-Adenina Dinucleotídeo/metabolismo , Ácido Fólico/metabolismo , Formiatos/metabolismo , Glicina/metabolismo , Mitocôndrias/metabolismo , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo
15.
Zhongguo Zhong Yao Za Zhi ; 47(8): 2134-2147, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35531729

RESUMO

An UPLC-Q-TOF-MS method was employed to characterize and classify the chemical components of the standard decoction of Yiguanjian, a classical famous recipe. Chromatographic separation was performed on an Acquity HSS T3(2.1 mm ×100 mm, 1.8 µm) column with a mobile phase of 0.1% formic acid water-0.1% formic acid acetonitrile using gradient elution. The flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry was performed on electrospray ionization source(ESI) with positive and negative ion scanning modes. The potential compounds were identified by comparing the reference compounds, analyzing the mass spectrometry data and matching the published articles on Masslynx 4.1 software and SciFinder database. Finally, a total of 113 compounds, including 11 amino acids, 19 terpenoids, 13 phthalides, 11 steroidal saponins, 10 coumarins, 9 alkaloids, 7 flavonoids, 8 phenylethanoid glycosides, 8 organic acids and 17 other categories were identified. The established method systematically and accurately characterized the chemical components in Yiguanjian, which could provide experimental evidences for the subsequent studies on the pharmacodynamical material basis and quality control of Yiguanjian.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Formiatos , Glicosídeos/análise , Prescrições
16.
Molecules ; 27(4)2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35209098

RESUMO

Sixteen organic acids were quantified in peel and pulp of Amber, Laird's Large and Mulligan cultivars of tamarillo using GC-MS. Fourteen of these compounds had not previously been quantified in tamarillo. An untargeted metabolomics approach was used in parallel to identify and quantify 64 more metabolites relative to the internal standard, indicating abundances of glutamic acid, pro-line, aspartic acid and γ-aminobutyric acid as well as lower concentrations of several other essential fatty acids and amino acids. The main findings were that total organic acid concentration was significantly higher (p < 0.05) in pulp than in peel, with the highest concentration seen in Mulligan pulp (219.7 mg/g DW). Remarkably, after citric acid, the potent bactericide itaconic acid was the second most abundant organic acid. At least 95% of organic acids in tamarillo were one of these two acids, as well as cis-aconitic, malic and 4-toluic acids. Differences between cultivar chemotypes were as substantial as differences between tissues. These results suggest that the bitter flavour of the peel does not result from organic acids. The combination of targeted and untargeted metabolomics techniques for simultaneous qualitative and quantitative investigation of nutrients and flavours is efficient and informative.


Assuntos
Ácidos/análise , Formiatos/química , Cromatografia Gasosa-Espectrometria de Massas , Compostos Orgânicos/análise , Solanum/química , Ácidos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metaboloma , Metabolômica/métodos , Compostos Orgânicos/metabolismo , Reprodutibilidade dos Testes , Solanum/metabolismo
17.
Chemosphere ; 291(Pt 1): 132710, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34718028

RESUMO

Recycling mining wastes to produce cemented tailings backfill (CTB) is the optimal approach to eliminate the environmental pollution caused by their accumulation. However, its low strength limits its application. Using calcium formate (CF) as an accelerator for improving its mechanical properties is of great significance to promote sustainable development. The effects of CF dosage and curing time on dilatancy deformation, compressive strength and microstructure of CTB were investigated through mechanical compression, scanning electron microscope (SEM) and energy dispersive spectrometer (EDS) tests. The strengthening and deterioration mechanisms of CF dosage on CTB were revealed, and its engineering practicability was systematically evaluated. The results show that the variation of volumetric strain in the dilatancy deformation stage firstly increase and then decrease with the increases of CF dosage and curing time. The relationship between CF dosage and compressive strength can be characterized by quadratic polynomial, and the optimal CF dosage characterizing the superior mechanical property of CTB is between 1.60 and 1.84. The supplement of CF reduces the size and distribution of microcracks and micropores, thereby optimizing the microstructure of CTB. Nevertheless, the excessive dosages of CF deteriorate the microstructure of CTB and produce serious defects, which cannot be effectively filled by hydration products, thus weakening the strength property of CTB. This study provides an effective accelerator for improving the mechanical properties of CTB, which is of great significance to promote the recycling of tailings.


Assuntos
Materiais de Construção , Mineração , Força Compressiva , Formiatos , Reciclagem
18.
Artigo em Chinês | WPRIM | ID: wpr-928153

RESUMO

An UPLC-Q-TOF-MS method was employed to characterize and classify the chemical components of the standard decoction of Yiguanjian, a classical famous recipe. Chromatographic separation was performed on an Acquity HSS T3(2.1 mm ×100 mm, 1.8 μm) column with a mobile phase of 0.1% formic acid water-0.1% formic acid acetonitrile using gradient elution. The flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry was performed on electrospray ionization source(ESI) with positive and negative ion scanning modes. The potential compounds were identified by comparing the reference compounds, analyzing the mass spectrometry data and matching the published articles on Masslynx 4.1 software and SciFinder database. Finally, a total of 113 compounds, including 11 amino acids, 19 terpenoids, 13 phthalides, 11 steroidal saponins, 10 coumarins, 9 alkaloids, 7 flavonoids, 8 phenylethanoid glycosides, 8 organic acids and 17 other categories were identified. The established method systematically and accurately characterized the chemical components in Yiguanjian, which could provide experimental evidences for the subsequent studies on the pharmacodynamical material basis and quality control of Yiguanjian.


Assuntos
Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Formiatos , Glicosídeos/análise , Prescrições
19.
Poult Sci ; 100(12): 101476, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34710711

RESUMO

After being banned by the European Commission in 2018, the use of formaldehyde as a feed amendment in the United States has come into question. Therefore, this study was conducted to explore alternatives to formaldehyde, such as formic acid and monoglycerides, and their effects on poultry production. In total, 1,728 Cobb 700 broilers were randomly assigned to 96-floor pens on day of hatch (18 birds/pen). Using a randomized complete block design (4 blocks), treatments were assigned to pens with blocking based on location within the barn, with the eastern half of the barn designated for digestibility and the western half designated for production (per experiment: 8 control pens and 10 pens per treatment). All diets were based on a negative control (NC), basal diet. Dietary treatments consisted of: NC, NC + 0.25% formalin (F), NC + 0.25 and 0.50% Amasil NA (AML and AMH; 61% formic acid and 20.5% Na-formate), and NC + SILO Health 104L (SILO; mixture of monoglycerides; 0.5% from 0 to 14 d, 0.4% from 14 to 28 d, and 0.2% from 28 to 42 d). Water and feed were provided ad libitum. Performance data were collected during feed changes on d 0, 14, 28, and 42, with digestibility data collected at d 14 (2 per pen) and carcass quality (6 per pen) assessed at d 46 with a randomly selected group of broilers. A one-way ANOVA followed by Dunnett's multiple comparison, where treatments were evaluated against F were conducted using JMP 14.0 (P ≤ 0.05). Main effect of treatment was significant for performance, nutrient digestibility, and carcass quality. Differences in body weight and ADG were observed from d 14 to d 28, resulting in a trending improvement in lysine digestibility on d 14 and carcass quality on d 46 of birds fed AML and AMH in comparison to those fed F (P < 0.05). Whereas birds fed SILO had reduced digestibility of methionine on d 14 and a decrease in meat quality on d 46 in comparison to those fed F (P < 0.05). Therefore, Amasil NA at 0.25 or 0.50% may be an effective alternative to formaldehyde as a feed amendment for poultry production.


Assuntos
Ração Animal , Galinhas , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Suplementos Nutricionais , Formaldeído , Formiatos , Carne , Monoglicerídeos , Nutrientes , Distribuição Aleatória
20.
Poult Sci ; 100(8): 101214, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34186268

RESUMO

The objective of this study was to evaluate the effect of 2 different doses of a partially buffered formic acid product (Amasil NA; 61% formic acid, 20.5% sodium formate), and a monoglyceride blend of short- and medium-chain fatty acids (BalanGut LS P) on necrotic enteritis (NE) infected broilers in terms of performance, intestinal microbial population and short-chain fatty acids concentrations in the gastrointestinal tract. A total of 528-day-old as hatched Ross 308 broilers were allocated to 48 pens with 11 birds in each pen. Six dietary treatments applied in the study were: T1) nonsupplemented diet (Control); T2) antibiotic supplemented diets; T3) and T4) high (Starter: 0.5%; Grower and Finisher: 0.5%) and low (Starter: 0.3%; Grower and Finisher: 0.2%) dose of Amasil NA; and groups T5) and T6) high (Starter: 0.3%; Grower and Finisher: 0.2%) and low dose (Starter: 0.3%; Grower: 0.15%; Finisher: 0.075%) of (BalanGut LS P). All birds in this study were fed starter (d 0-10), grower (d 11-24) and finisher (d 25-35) diets and challenged with NE. To induce subclinical NE, oral administrations of Eimeria oocysts (d 9) followed by inoculation of Clostridium perfringens strains (d 14 and 15) were applied. Results showed that birds fed the high dose of Amasil NA, had a higher feed conversion ratio (FCR,P < 0.05) compared to the nonsupplemented group during the starter period. Antibiotic supplementation reduced FCR during the grower (P < 0.001), finisher (P < 0.05) and overall (P < 0.001) periods of the experiment. Both levels of BalanGut LS P and low levels of Amasil NA enhanced overall FCR (P < 0.05) compared to the birds in the nonsupplemented group. Compared to the nonsupplemented group, high levels of Amasil NA and low levels of BalanGut LS P improved FCR in the finisher stage (P < 0.05). On d 16, cecum digesta of birds fed with antibiotic supplemented diets showed a significantly lower number of C. perfringens (P < 0.001) compared to the nonsupplemented and high level of BalanGut LS P group. Bacillus (P < 0.01) and Ruminococcus numbers were significantly lower in the birds fed with high level of Amasil NA (P < 0.05) compared to the antibiotic supplemented diets. High doses of Amasil NA, showed the highest propionate concentration in the cecum (P < 0.001). The study suggests that supplementation of BalanGut LS P and Amasil NA at different feeding phases may achieve optimal performance improvement in broilers under NE challenge.


Assuntos
Infecções por Clostridium , Enterite , Doenças das Aves Domésticas , Ração Animal/análise , Animais , Galinhas , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/veterinária , Dieta/veterinária , Suplementos Nutricionais , Enterite/tratamento farmacológico , Enterite/prevenção & controle , Enterite/veterinária , Formiatos , Monoglicerídeos , Doenças das Aves Domésticas/tratamento farmacológico
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