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1.
Bioresour Technol ; 341: 125757, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34411942

RESUMO

Glycolic acid has chemical properties similar to those of formic acid. Therefore, similar to formic acid pretreatment, glycolic acid pretreatment has the separation effect of hemicellulose. In this study, eucalyptus hemicellulose was effectively separated by glycolic acid pretreatment. The effects of glycolic acid concentration, temperature and time on the separation of cellulose, hemicellulose and lignin were investigated. The optimum conditions were acid concentration 5.40%, temperature 140 °C, time 3.0 h. The highest yield of xylose was 56.72%. The recovery rate of glycolic acid was 91%. Compared to formic acid, the yield of xylose increased to 10.33% while that of lignin decreased to 11.08%. It showed high selectivity for hemicellulose separation, yielding 65.48% hemicellulose with 72.08% purity. The depolymerization and repolymerization of lignin were inhibited. The integrity of the cellulose structure was preserved. It provides theoretical support for the fractional separation and high-value transformation of lignocellulosic biomass.


Assuntos
Eucalyptus , Biomassa , Glicolatos , Hidrólise , Lignina , Polissacarídeos
2.
Molecules ; 26(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34361546

RESUMO

The adsorption of retinol, niacinamide and glycolic acid active ingredients on the internal surface of halloysite in an aqueous environment was explored at the molecular level by means of calculations based on quantum mechanics and force fields from empirical interatomic potentials. These active ingredients are stably adsorbed on the internal surface of halloysite forming hydrogen bonds between the hydrogen, oxygen and nitrogen atoms with the hydroxyl groups of the inner surface of the halloysite. In addition, electrostatic interaction between these active ingredients with the water molecules was observed. Therefore, the theoretical results indicate that the adsorption of these active principles is favourable in the halloysite nanotube, which allows directing future experimental investigations for the development and design of retinol, niacinamide and glycolic acid with halloysite nanotubes systems, which may be topical formulations for skincare.


Assuntos
Argila/química , Glicolatos , Niacinamida , Higiene da Pele , Vitamina A , Administração Tópica , Glicolatos/química , Glicolatos/farmacologia , Humanos , Niacinamida/química , Niacinamida/farmacologia , Vitamina A/química , Vitamina A/farmacologia
3.
Ann Clin Lab Sci ; 51(4): 584-586, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452901

RESUMO

In this study, we evaluated the analytical interference of glycolic acid on several lactate assays that use lactate oxidase and dehydrogenase. Herein, we tested the effect of different concentrations of glycolic acid (0.01-46mM) on the lactate assay by using central lab and point of care (POCT) analyzers: Radiometer ABL 800, Beckman AU480, Roche Cobas c502, and Abbott i-STAT. Glycolic acid concentrations as low as 0.12mM resulted in a ≥20% positive bias in lactate assay on the ABL 800 and a concentration of approximately 0.23mM resulted in >20% on the Roche Cobas c502 and Abbott i-STAT. A significant lactate gap is found at concentrations >0.06mM between the Radiometer ABL 800 and Roche Cobas c502/Abbott i-STAT. However, at concentrations ≥0.92mM, the lactate gap is very significant among all three platforms. Falsely elevated lactate levels could result in misdiagnosis.


Assuntos
Bioensaio/normas , Erros de Diagnóstico/prevenção & controle , Glicolatos/envenenamento , Ácido Láctico/sangue , Sistemas Automatizados de Assistência Junto ao Leito/normas , Diagnóstico Diferencial , Humanos
4.
J Biomed Nanotechnol ; 17(7): 1320-1329, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446135

RESUMO

Nanoparticles (NPs) are a promising strategy for delivering drugs to specific sites because of their tunable size and surface chemistry variety. Among the availablematerials, NPs prepared with biopolymers are of particular interest because of their biocompatibility and controlled release of encapsulated drugs. Poly lactic-co-glycolic acid (PLGA) is one of the most widely used biopolymers in biomedical applications. In addition to material choice modulation of the interaction between NPs and biological systems is essential for the safety and effective use of NPs. Therefore, this work focused on evaluating different surface functionalization strategies to promote cancer cell uptake and intracellular targeting of PLGA NPs. Herein, cell-penetrating peptides (CPPs) were shown to successfully drive PLGA NPs to the mitochondria and nuclei. Furthermore, the functionalization of PLGA NPs with peptide AC-1001 H3 (GQYGNLWFAY) was proven to be useful for targeting actin filaments. The PLGA NPs cell internalization mechanism by B16F10-Nex2 cells was identified as caveolae-mediated endocytosis, which could be inhibited by the presence of methyl-ß-cyclodextrin. Notably, when peptide C (CVNHPAFAC) was used to functionalize PLGA NPs, none of the tested inhibitors could avoid cell internalization of PLGA NPs. Therefore, we suggest this peptide as a promising surface modification agent for enhancing drug delivery to cancer cells. Finally, PLGA NPs showed slow release kinetics and low cytotoxic profile, which, combined with the surface functionalization strategies addressed in this study, highlight the potential of PLGA NPs as a drug delivery platform for improving cancer therapy.


Assuntos
Peptídeos Penetradores de Células , Nanopartículas , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Glicolatos , Glicóis , Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
5.
J Biotechnol ; 335: 39-46, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34090947

RESUMO

The green alga Chlamydomonas reinhardtii serves as a model organism for plant and photosynthesis research due to many commonalities in metabolism and to the fast growth rate of C. reinhardtii which accelerates experimental turnaround time. In addition, C. reinhardtii is a focus of research efforts in metabolic engineering and synthetic biology for the potential production of biofuels and value-added chemicals. Here, we report that the C. reinhardtii cia5 mutant, which lacks a functional carbon-concentrating mechanism (CCM), can produce substantial amounts of glycolate, a high-value cosmetic ingredient, when the mutant is cultured under ambient air conditions. In order to reveal the metabolic basis of glycolate accumulation by the cia5 mutant, we investigated the metabolomes of the cia5 mutant and a wild type strain CC-125 (WT) through the global metabolic profiling of intracellular and extracellular fractions using gas chromatography and mass spectrometry. We observed the intracellular and extracellular metabolic profiles of the WT and the cia5 mutant were similar during the mixotrophic phase at 30 h. However, when the cells entered the photoautotrophic phase (i.e., 96 h and 120 h), both the intracellular and extracellular metabolic profiles of cia5 mutant differed significantly when compared to WT. In the cia5 mutant strain, a group of photorespiration pathway intermediates including glycolate, glyoxylate, glycine, and serine accumulated to significantly higher levels compared to WT. In the photorespiration pathway, glycolate is metabolized to glyoxylate and glycine leading to NH3 and CO2 generation during the mitochondrial conversion of glycine to serine. This result provides further evidence that the CIA5 mutation increased the photorespiration rate. Because the cia5 mutant lacks a CCM, and C. reinhardtii might harbor an inefficient or incomplete photorespiration pathway, glycolate may accumulate when the CCM is not functional. We envision that investigating photorespiration controls in C. reinhardtii provides tools for producers to use the cia5 mutant to produce glycolate as well as platform to engineer alternative pathways for glycolate metabolism.


Assuntos
Chlamydomonas reinhardtii , Carbono , Dióxido de Carbono , Chlamydomonas reinhardtii/genética , Cromatografia Gasosa-Espectrometria de Massas , Glicolatos , Fotossíntese/genética
6.
Analyst ; 146(14): 4615-4621, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34164639

RESUMO

The detection of explosive nitroaromatic compounds has caused worldwide concern for human safety. In this study, we introduce a fluorescent biosensor based on porous biocompatible microspheres loaded with a bioreporter for the detection of nitroaromatic compounds. Poly(lactic-co-glycolic acid) microbeads were designed as biosensors embedded with the bacterial bioreporters. The genetically engineered bacterial bioreporter can express a green fluorescent protein in response to nitroaromatic compounds (e.g., trinitrotoluene and dinitrotoluene). The modified surface structure in microbeads provides a large surface area, as well as easy penetration, and increases the number of attached bioreporters for enhanced fluorescent signals of biosensors. Moreover, the addition of the M13 bacteriophage in open porous microbeads significantly amplified the fluorescence signal for detection by the π-π interaction between peptides in the M13 bacteriophage and nitroaromatic compounds. The modification of the surface morphology, as well as the genetically engineered M13 phage, significantly amplifies the fluorescence signal, which makes the detection of explosives easier, and has great potential for the stand-off remote sensing of TNT buried in the field.


Assuntos
Substâncias Explosivas , Trinitrotolueno , Bactérias , Glicolatos , Glicóis , Humanos , Microesferas , Porosidade
7.
Dermatol Ther ; 34(4): e15025, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34089564

RESUMO

Melasma is a disfiguring dermatologic condition and its treatment is still considered a challenge. To evaluate the efficacy and safety of microdermabrasion (MDA) combined with glycolic acid 70% (GA70%) peel versus GA70% alone in treating melasma in dark-skinned patients. This study included 30 female patients (skin type IV and V) with melasma. After cleansing the face, 3 passes of MDA were done on one side of the face. Then, GA70% was applied to the whole face in 1-2 uniform passes. Melasma area and severity index (MASI), modified MASI and hemi-MASI scores were used to assess the outcome. A significant decline of the mean MASI, mMASI and both hemi-MASI scores following treatment (p value = 0.000 for each). Furthermore, the hemi-MASI score on the MDA/GA70% treated side showed significantly greater decrease than the hemi-MASI score on GA70% treated side (p value = 0.041). MDA enhanced the improvement of GA70% peel effectively and safely.


Assuntos
Abrasão Química , Melanose , Abrasão Química/efeitos adversos , Feminino , Glicolatos/efeitos adversos , Humanos , Melanose/diagnóstico , Melanose/terapia , Resultado do Tratamento
8.
Dent Mater J ; 40(5): 1196-1201, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34024884

RESUMO

In guided bone regeneration (GBR), a barrier membrane is applied to provide a space for bone regeneration to promote cell adhesion, cell proliferation, and bone regeneration by inducing cell migration to the surface of the bone-deficient site. We prepared a non-woven absorbable membrane for GBR comprised of a copolymer of L-lactic acid and glycolic acid (PLLGA) using the dry spinning method. A thin and dense membrane comprising unsintered hydroxyapatite (uHA) and poly-L-lactic acid (PLLA) was used for comparison. Osteoblast TMS-12 cells were seeded onto the membranes, and cell adhesion and proliferation rates were examined. Calcification levels were quantified by Alizarin Red S staining after cell culture in calcification induction medium. Osteoblastic gene expression was examined by RT-PCR. Cell adhesion and proliferation rates and calcification on PLLGA membranes were significantly higher than those on uHA/PLLA membranes. PLLGA membranes upregulated osteogenic gene expression compared to on uHA/PLLA membranes. Non-woven PLLGA membranes may be useful in GBR for promoting bone formation and maturation.


Assuntos
Ácido Láctico , Poliésteres , Regeneração Óssea , Glicolatos , Membranas Artificiais , Osteoblastos
9.
Zhongguo Zhong Yao Za Zhi ; 46(10): 2481-2488, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047094

RESUMO

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 µg·mL~(-1) and 0.66 µg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.


Assuntos
Antineoplásicos Fitogênicos , Neoplasias do Colo do Útero , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Portadores de Fármacos , Feminino , Ácido Fólico , Glicolatos , Células HeLa , Humanos , Micelas , Paclitaxel , Tamanho da Partícula , Neoplasias do Colo do Útero/tratamento farmacológico
10.
Forensic Sci Int ; 324: 110833, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34020075

RESUMO

GHB related acids (3,4-dihydroxy butyric acid, 2,4-dihydroxy butyric acid and glycolic acid) are produced through oxidative GHB metabolism. These analytes could be potential biomarkers to ensure the diagnosis of a GHB intoxication and even prolong the detection window. Within this study, forensic routine cases were measured to consider the potential of additional gas chromatographic mass spectrometric analysis on these acids. 17 GHB positive real cases (10 serum samples and 7 urine samples) and 40 cases with suspicion of drugging in DFC cases and negative GHB results (21 serum samples and 19 urine samples) were evaluated. Increased GHB related acid concentrations were detected in all serum and most urine samples positive on GHB. In some GHB negative cases, especially in serum samples, concentrations of GHB related acids gave hints that GHB actually was taken. We recommend to use the following cut-offs for a more reliable interpretation of potential GHB intoxication cases: 3,4-OH-BA:>3 mg/L in serum and>50 mg/L in urine; 2,4-OH-BA:>2 mg/L in serum and>25 mg/L in urine; GA:>5 mg/L in serum and>400 mg/L in urine.


Assuntos
Envenenamento/diagnóstico , Oxibato de Sódio/análise , Biomarcadores/análise , Ácido Butírico/análise , Toxicologia Forense/métodos , Cromatografia Gasosa-Espectrometria de Massas , Glicolatos/análise , Humanos , Oxibato de Sódio/envenenamento , Ácido Succínico/análise
11.
Appl Environ Microbiol ; 87(12): e0011321, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33837017

RESUMO

Glycolate is widely used in industry, especially in the fields of chemical cleaning, cosmetics, and medical materials, and has broad market prospects for the future. Recent advances in metabolic engineering and synthetic biology have significantly improved the titer and yield of glycolate. However, an expensive inducer was used in previous studies, which is not feasible for use in large-scale industrial fermentations. To constitutively biosynthesize glycolate, the expression level of each gene of the glycolate synthetic pathway needs to be systemically optimized. The main challenge of multigene pathway optimization is being able to select or screen the optimum strain from the randomly assembled library by an efficient high-throughput method within a short time. To overcome these challenges, we firstly established a glycolate-responsive biosensor and developed agar plate- and 48-well deep-well plate-scale high-throughput screening methods for the rapid screening of superior glycolate producers from a large library. A total of 22 gradient-strength promoter-5'-untranslated region (UTR) complexes were randomly cloned upstream of the genes of the glycolate synthetic pathway, generating a large random assembled library. After rounds of screening, the optimum strain was obtained from 6 × 105 transformants in a week, and it achieved a titer of 40.9 ± 3.7 g/liter glycolate in a 5-liter bioreactor. Furthermore, high expression levels of the enzymes YcdW and GltA were found to promote glycolate production, whereas AceA has no obvious impact on glycolate production. Overall, the glycolate biosensor-based pathway optimization strategy presented in this work provides a paradigm for other multigene pathway optimizations. IMPORTANCE The use of strong promoters, such as pTrc and T7, to control gene expression not only needs the addition of expensive inducers but also results in excessive protein expression that may result in unbalanced metabolic flux and the waste of cellular building blocks and energy. To balance the metabolic flux of glycolate biosynthesis, the expression level of each gene needs to be systemically optimized in a constitutive manner. However, the lack of high-throughput screening methods restricted glycolate synthetic pathway optimization. Our work firstly established a glycolate-response biosensor, and agar plate- and 48-well plate-scale high-throughput screening methods were then developed for the rapid screening of optimum pathways from a large library. Finally, we obtained a glycolate-producing strain with good biosynthetic performance, and the use of the expensive inducer isopropyl-ß-d-thiogalactopyranoside (IPTG) was avoided, which broadens our understanding of the mechanism of glycolate synthesis.


Assuntos
Proteínas de Bactérias/genética , Técnicas Biossensoriais , Escherichia coli/genética , Glicolatos/metabolismo , Proteínas de Bactérias/metabolismo , Reatores Biológicos , Escherichia coli/metabolismo , Fermentação , Regulação Bacteriana da Expressão Gênica , Ensaios de Triagem em Larga Escala , Engenharia Metabólica , Plasmídeos , Regiões Promotoras Genéticas
12.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800748

RESUMO

The plant hormone indole-3-acetic acid (IAA) is one of the main signals playing a role in the communication between host and endophytes. Endophytes can synthesize IAA de novo to influence the IAA homeostasis in plants. Although much is known about IAA biosynthesis in microorganisms, there is still less known about the pathway by which IAA is synthesized in fungal endophytes. The aim of this study is to examine a possible IAA biosynthesis pathway in Cyanodermella asteris. In vitro cultures of C. asteris were incubated with the IAA precursors tryptophan (Trp) and indole, as well as possible intermediates, and they were additionally treated with IAA biosynthesis inhibitors (2-mercaptobenzimidazole and yucasin DF) to elucidate possible IAA biosynthesis pathways. It was shown that (a) C. asteris synthesized IAA without adding precursors; (b) indole-3-acetonitrile (IAN), indole-3-acetamide (IAM), and indole-3-acetaldehyde (IAD) increased IAA biosynthesis; and (c) C. asteris synthesized IAA also by a Trp-independent pathway. Together with the genome information of C. asteris, the possible IAA biosynthesis pathways found can improve the understanding of IAA biosynthesis in fungal endophytes. The uptake of fungal IAA into Arabidopsis thaliana is necessary for the induction of lateral roots and other fungus-related growth phenotypes, since the application of the influx inhibitor 2-naphthoxyacetic acid (NOA) but not the efflux inhibitor N-1-naphtylphthalamic acid (NPA) were altering these parameters. In addition, the root phenotype of the mutation in an influx carrier, aux1, was partially rescued by C. asteris.


Assuntos
Arabidopsis/microbiologia , Ascomicetos/metabolismo , Endófitos/metabolismo , Adaptação ao Hospedeiro , Ácidos Indolacéticos/metabolismo , Indóis/farmacologia , Raízes de Plantas/microbiologia , Triptofano/farmacologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Ascomicetos/efeitos dos fármacos , Ascomicetos/genética , Benzimidazóis/farmacologia , Meios de Cultivo Condicionados , Genoma Fúngico , Glicolatos/farmacologia , Especificidade de Hospedeiro , Ácidos Indolacéticos/farmacologia , Indóis/metabolismo , Redes e Vias Metabólicas/genética , Ftalimidas/farmacologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Triazóis/farmacologia , Triptofano/metabolismo
13.
Photodiagnosis Photodyn Ther ; 34: 102286, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33838311

RESUMO

BACKGROUND: In this study, the ability of antimicrobial photodynamic therapy (aPDT) as a treatment approach and adjuvant therapy using curcumin-poly (lactic-co-glycolic acid) nanoparticles (Cur@PLGA-NPs) to inactivate Coronavirus disease 2019 (COVID-19) in plasma was investigated. Furthermore, to verify whether the quality requirement of aPDT-treated plasma is acceptable, the differences of the levels of clotting factors, total plasma proteins, and anti-A and/or anti-B antibodies titrations in plasma of patient before and after aPDT treatment were investigated. MATERIALS AND METHODS: Cur@PLGA-NPs was synthesized using Electrospinning process and characterized by different analysis including Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), and Fourier Transform Infrared (FTIR) spectroscopy assays. The presence of the SARS-CoV-2 in the plasma samples of patients suspected of having COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Then, the treated plasma samples with Cur@PLGA-NPs plus blue laser were exposed to Vero cells. Eventually, cell cytotoxicity and apoptotic effects of treated Vero cells were evaluated. Levels of clotting factors including prothrombin time (PT) and activated partial thromboplastin time (APTT), total plasma proteins, and anti-A and/or anti-B antibodies measurements were performed using the coagulometer, method of Bradford, and titration procedure, respectively. RESULTS: The presence of SARS-CoV-2 was positive in 84.3 % of samples. Different concentrations of Cur@PLGA-NPs (3, 5, 7, and 10 % wt.), the irradiation times of blue laser (1, 3, and 5 min), and aPDT with the maximum dosed of blue laser light (522.8 J/cm2) plus 10 % wt. Cur@PLGA-NPs had no cytotoxicity. Although there were significant cell degradation and apoptotic effects in treated Vero cells with treated plasma using 10 % wt. Cur@PLGA-NPs, and a blue laser at an energy density of 522.8 J/cm2, no visible changes in cells and apoptosis were observed following aPDT. Total plasma protein content, PT, APTT, and anti-A and/or anti-B antibodies titers showed no significant changes (P > 0.05 for all comparisons) in treated plasma as compared to untreated plasma. CONCLUSION: aPDT exhibited in vitro anti-COVID-19 activities in the treated plasma containing SARS-COV-2 without Vero cell apoptosis and any adverse effects on plasma quality in aPDT-exposed plasma.


Assuntos
COVID-19 , Curcumina , Nanopartículas , Fotoquimioterapia , Animais , Antibacterianos , Linhagem Celular , Chlorocebus aethiops , Curcumina/farmacologia , Glicolatos , Glicóis , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , SARS-CoV-2 , Células Vero
14.
Phys Rev Lett ; 126(8): 088102, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33709739

RESUMO

The interaction between proteins and hydration water stabilizes protein structure and promotes functional dynamics, with water translational motions enabling protein flexibility. Engineered solvent-free protein-polymer hybrids have been shown to preserve protein structure, function, and dynamics. Here, we used neutron scattering, protein and polymer perdeuteration, and molecular dynamics simulations to explore how a polymer dynamically replaces water. Even though relaxation rates and vibrational properties are strongly modified in polymer coated compared to hydrated proteins, liquidlike polymer dynamics appear to plasticize the conjugated protein in a qualitatively similar way as do hydration-water translational motions.


Assuntos
Polímeros/química , Proteínas/química , Diaminas/química , Glicolatos/química , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Mioglobina/química , Difração de Nêutrons , Polietilenoglicóis/química , Conformação Proteica , Termodinâmica , Água/química
15.
J Chromatogr A ; 1642: 462037, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33714768

RESUMO

Two solid phase extraction resins (SPER) were prepared by impregnating solutions of two diglycolamide-functionalized calix[4]arenes in 10% isodecanol in n-dodecane into Chromosorb W, as the stationary phase. While SPER-I contained n-propyl functionalized calix[4]arene, SPER-II contained the calix[4]arene with isopentyl groups at the carboxamide nitrogen atoms. The SPERs were characterized by SEM, TGA, FTIR, etc. and were used for the batch uptake of neptunium(IV) from nitric acid feed solutions. While the uptake of Np(IV) was extremely high with SPER-I (Kd: 47,544 at 3 M nitric acid, ca. 8% extractant loading), SPER-II displayed a significantly lower extraction efficiency (Kd: 13,724 under identical conditions) as indicated by the batch uptake studies. Sorption isotherm studies were carried out which indicated good fitting to the Langmuir model suggesting uptake conforming to monolayer sorption. Fitting to the D-R isotherm model conformed to a chemisorption model. Column studies were also carried out and the elution profiles, obtained with solutions of oxalic acid and nitric acid indicated very sharp peaks suggesting that the column can be used for the separation of Np(IV) from acidic radioactive feeds.


Assuntos
Calixarenos/química , Glicolatos/química , Netúnio/análise , Ácido Nítrico/química , Fenóis/química , Resinas Sintéticas/química , Extração em Fase Sólida/métodos , Adsorção , Íons , Cinética , Ligantes , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Termogravimetria , Fatores de Tempo
16.
ACS Chem Biol ; 16(3): 463-470, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33688722

RESUMO

The isocitrate lyases (ICL1/2) are essential enzymes of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. At present, no ICL1/2 inhibitors have progressed to clinical evaluation, despite extensive drug discovery efforts. Herein, we surveyed succinate analogs against ICL1 and found that dicarboxylic acids constrained in their synperiplanar conformations, such as maleic acid, comprise uncompetitive inhibitors of ICL1 and inhibit more potently than their trans-isomers. From this, we identified cis-2,3 epoxysuccinic acid (cis-EpS) as a selective, irreversible covalent inactivator of Mtb ICL1 (kinact/Kinact= (5.0 ± 1.4) × 104 M-1 s-1; Kinact = 200 ± 50 nM), the most potent inactivator of ICL1 yet characterized. Crystallographic and mass spectrometric analysis demonstrated that Cys191 of ICL1 was S-malylated by cis-EpS, and a crystallographic "snapshot" of inactivation lent insight into the chemical mechanism of this inactivation. Proteomic analysis of E. coli lysates showed that cis-EpS selectively labeled plasmid-expressed Mtb ICL1. Consistently, cis-EpS, but not its trans-isomer, inhibited the growth of Mtb under conditions in which ICL function is essential. These findings encourage the development of analogs of cis-2,3-epoxysuccinate as antituberculosis agents.


Assuntos
Antituberculosos/química , Inibidores Enzimáticos/química , Isocitrato Liase/antagonistas & inibidores , Mycobacterium tuberculosis/enzimologia , Succinatos/química , Tuberculose/tratamento farmacológico , Antituberculosos/metabolismo , Descoberta de Drogas , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Escherichia coli/metabolismo , Glicolatos/química , Glioxilatos/química , Humanos , Isomerismo , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Proteômica , Succinatos/metabolismo , Termodinâmica
17.
Biochem Biophys Res Commun ; 551: 161-167, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33740623

RESUMO

Physiological oxygen concentration (physioxia) ranges from 1 to 8% in human tissues while many researchers cultivate mammalian cells under an atmospheric concentration of 21% (hyperoxia). Oxygen is one of the significant gases which functions in human cells including energy production in mitochondria, metabolism in peroxidase, and transcription of various genes in company with HIF (Hypoxia-inducible factors) in the nucleus. Thus, mammalian cell culture should be deliberated on the oxygen concentration to mimic in vivo physiology. Here, we studied if the cultivation of human skin cells under physiological conditions could affect skin significant genes in barrier functions and dermal matrix formation. We further examined that some representative active ingredients in dermatology such as glycolic acid, gluconolactone, and salicylic acid work in different ways depending on the oxygen concentration. Taken together, we present the importance of oxygen concentration in skin cell culture for proper screening of novel ingredients as well as the mechanistic study of skin cell regulation.


Assuntos
Hidroxiácidos/farmacologia , Oxigênio/farmacologia , Pele , Linhagem Celular , Colágeno Tipo I/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Gluconatos/metabolismo , Glicolatos/metabolismo , Humanos , Queratina-1/genética , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Lactonas/metabolismo , Metaloproteinase 1 da Matriz/genética , Oxigênio/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/genética , Proteínas S100/genética , Ácido Salicílico/metabolismo , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo
18.
Forensic Sci Int ; 320: 110717, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33578180

RESUMO

Fluroxypyr-meptyl and triclopyr are synthetic auxin-like herbicides that are used to control woody and broadleaf weeds. Herein, we report a case of fatal intoxication involving fluroxypyr-meptyl and triclopyr. A 61-year-old man was found dead at his farm with several suicide notes, and a white plastic bottle and a plastic cup with traces of white emulsion were found next to him. The plastic bottle was labeled as an herbicide formulation containing fluroxypyr-meptyl and triclopyr. Forensic toxicological screening of the stomach contents revealed the presence of fluroxypyr-meptyl, fluroxypyr and triclopyr. However, no fluroxypyr-meptyl was detected in blood owing to its rapid hydrolysis to fluroxypyr. In this study, fluroxypyr and triclopyr in blood were extracted using solid-phase extraction, and analyzed by liquid chromatography-tandem mass spectrometry. The analytical method was validated in terms of linearity, precision, accuracy, recovery and matrix effect, and the acceptable criteria were satisfied. Toxicological analysis showed that fluroxypyr and triclopyr concentrations were 19.7 µg/mL and 137.4 µg/mL in peripheral blood and 16.5 µg/mL and 147.8 µg/mL in heart blood, respectively. Based on these toxicological results and autopsy findings, the cause of death was determined to be acute fatal intoxication by ingestion of the pesticide containing fluroxypyr-meptyl and triclopyr. This is the first report of the determination of fluroxypyr and triclopyr in a fatal intoxication case.


Assuntos
Glicolatos/análise , Herbicidas/química , Herbicidas/envenenamento , Cromatografia Líquida , Toxicologia Forense , Glicolatos/sangue , Glicolatos/envenenamento , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Suicídio Consumado
19.
Mater Sci Eng C Mater Biol Appl ; 120: 111780, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545908

RESUMO

A physical barrier is one of the most effective strategies to alleviate excessive postoperative adhesion (POA) between tissues at an injury site. To overcome the limitations of current polymeric film-type physical barriers, we suggest a film of poly(lactic-co-glycolic acid) (PLGA) that is non-covalently coated with poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)) (PMB). While maintaining the degradability and mechanical properties of PLGA, the PMB coating introduces strong anti-adhesive properties to the film by forming a zwitterionic MPC-based surface through the hydrophobic interactions between BMA moieties and PLGA. Compared to SurgiWrap®, the commercially available poly(lactic acid)-based anti-adhesive film against POA, the PMB-coated PLGA film is much more inhibitory against protein adsorption and fibroblast adhesion, processes that are crucial to the POA process. PMB coating also inhibits the expression of fibronectin containing extra domain A (FN-EDA), α-smooth muscle actin (α-SMA), and collagen type IV alpha 2 (COL4A2), which are marker genes and proteins involved in fibroblast activation and excessive fibrosis during POA. Such inhibitory activities are clearly observed in a 3-dimensional culture of fibroblasts within a collagen matrix, which mimics the in vivo environment of an injury site, as well as in a 2-dimensional culture. The kinetics and the stability of the PMB coating suggest potential future clinical use to coat PLGA films to create a film-type anti-adhesion barrier that overcomes the limitations of current products.


Assuntos
Ácido Láctico , Polímeros , Adesão Celular , Glicolatos , Glicóis
20.
J Chromatogr A ; 1641: 461999, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33611122

RESUMO

Low molecular weight diglycolamide (DGA) extractants were tested for the extraction of europium(III) and americium(III) from nitric acid solutions in n-dodecane, a molecular diluent and 1-butyl-3-methylimidazolium bis(trifluoromethanesulphonyl) imide (C4mim⋅NTf2), a room temperature ionic liquid, as the diluents. N,N,N',N'-tetra-n-butyl diglycolamide (TBDGA) was selected for extraction chromatography (XC) studies involving Eu(III) and Am(III). While the TBDGA resin containing n-dodecane gave reasonably high Kd values, that containing the ionic liquid showed higher Eu(III) uptake values. Compared to Eu(III), Am(III) was extracted by the resins to a lower extent. The loaded Eu(III) was back extracted from the resin using 0.05 M EDTA solutions in a buffered medium containing 1 M guanidine carbonate. Reusability studies indicated that, while the ionic liquid-based resin can be conveniently recycled five times with very marginal decrease in the percentage extraction values, there was a sharp decrease in the percent extraction after three cycles with the n-dodecane-based resin. The uptake data was fitted into different isotherm models and the results conformed to the Langmuir model. Based on the batch uptake studies, columns were prepared and the breakthrough as well as elution profiles were obtained. The elution profiles were found to be sharp without any significant tailing.


Assuntos
Cromatografia/métodos , Glicolatos/química , Líquidos Iônicos/química , Ácido Nítrico/química , Resinas Sintéticas/química , Amerício/química , Cátions , Európio/química , Imidazóis/química , Ligantes , Solventes/química , Temperatura , Termogravimetria , Fatores de Tempo
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