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1.
Anal Chim Acta ; 1319: 342946, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39122268

RESUMO

BACKGROUND: Researchers have investigated different techniques for synthesis of carbon dots. These techniques include Arc discharge, laser ablation, oxidation, water/solvothermal, and chemical vapor deposition. However, these techniques suffer from some limitations like the utilization of gaseous charged particles, high current, high temperature, potent oxidizing agents, non-environmentally friendly carbon sources, and the generation of uneven particle size. Therefore, there was a significant demand for the adoption of a new technology that combines the environmentally friendly aspects of both bio-based carbon sourcing and synthesis technique. RESULTS: Medicago sativa L (alfalfa)-derived N, S-CDs have been successfully synthesized via microwave irradiation. The N,S-CDs exhibit strong fluorescence (λex/em of 320/420 nm) with fluorescence quantum yield of 2.2 % and high-water solubility. The produced N,S-CDs were characterized using TEM, EDX, Zeta potential analysis, IR, UV-Visible, and fluorescence spectroscopy. The average diameter of the produced N, S-CDs was 4.01 ± 1.2 nm, and the Zeta potential was -24.5 ± 6.63 mv. The stability of the produced nano sensors was also confirmed over wide pH range, long time, and in presence of different ions. The synthesized N, S-CDs were employed to quantify the antibacterial drug, nifuroxazide (NFZ), by fluorescence quenching via inner filter effect mechanism. The method was linear with NFZ concentration ranging from 1.0 to 30.0 µM. LOD and LOQ were 0.16 and 0.49 µM, respectively. The method was applied to quantify NFZ in simulated gastric juice (SGJ) with % recovery 99.59 ± 1.4 in addition to pharmaceutical dosage forms with % recovery 98.75 ± 0.61 for Antinal Capsules® and 100.63 ± 1.54 for Antinal suspension®. The Method validation was performed in compliance with the criteria outlined by ICH. SIGNIFICANCE AND NOVELTY: The suggested approach primarily centers on the first-time use of alfalfa, an ecologically sustainable source of dopped-CDs, and a cost-effective synthesis technique via microwave irradiation, which is characterized by low energy consumption, minimized reaction time, and the ability to control the size of the produced CDs. This is in line with the growing global recognition of the implementation of green analytical chemistry principles.


Assuntos
Biomassa , Suco Gástrico , Medicago sativa , Micro-Ondas , Nitrofuranos , Medicago sativa/química , Nitrofuranos/análise , Suco Gástrico/química , Química Verde , Hidroxibenzoatos/análise , Hidroxibenzoatos/química , Pontos Quânticos/química , Humanos , Tamanho da Partícula
2.
Viruses ; 16(8)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39205296

RESUMO

Chikungunya virus (CHIKV) is a reemerging arbovirus causing disease on a global scale, and the potential for its epidemics remains high. CHIKV has caused millions of cases and heavy economic burdens around the world, while there are no available approved antiviral therapies to date. In this study, nifuroxazide, an FDA-approved antibiotic for acute diarrhea or colitis, was found to significantly inhibit a variety of arboviruses, although its antiviral activity varied among different target cell types. Nifuroxazide exhibited relatively high inhibitory efficiency in yellow fever virus (YFV) infection of the hepatoma cell line Huh7, tick-borne encephalitis virus (TBEV) and west nile virus (WNV) infection of the vascular endothelial cell line HUVEC, and CHIKV infection of both Huh7 cells and HUVECs, while it barely affected the viral invasion of neurons. Further systematic studies on the action stage of nifuroxazide showed that nifuroxazide mainly inhibited in the viral replication stage. In vivo, nifuroxazide significantly reduced the viral load in muscles and protected mice from CHIKV-induced footpad swelling, an inflammation injury within the arthrosis of infected mice. These results suggest that nifuroxazide has a potential clinical application as an antiviral drug, such as in the treatment of CHIKV infection.


Assuntos
Antivirais , Febre de Chikungunya , Vírus Chikungunya , Hidroxibenzoatos , Nitrofuranos , Replicação Viral , Animais , Camundongos , Humanos , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/fisiologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Replicação Viral/efeitos dos fármacos , Nitrofuranos/farmacologia , Nitrofuranos/uso terapêutico , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/virologia , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/uso terapêutico , Linhagem Celular , Carga Viral/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana
3.
Molecules ; 29(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38999023

RESUMO

A series of 21 new 7'H-spiro[azetidine-3,5'-furo [3,4-d]pyrimidine]s substituted at the pyrimidine ring second position were synthesized. The compounds showed high antibacterial in vitro activity against M. tuberculosis. Two compounds had lower minimum inhibitory concentrations against Mtb (H37Rv strain) compared with isoniazid. The novel spirocyclic scaffold shows excellent properties for anti-tuberculosis drug development.


Assuntos
Antituberculosos , Azetidinas , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Nitrofuranos , Compostos de Espiro , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/farmacologia , Antituberculosos/química , Antituberculosos/síntese química , Azetidinas/química , Azetidinas/farmacologia , Nitrofuranos/farmacologia , Nitrofuranos/química , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Compostos de Espiro/síntese química , Relação Estrutura-Atividade , Estrutura Molecular
4.
Inorg Chem ; 63(32): 15134-15143, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39074382

RESUMO

Gossypol (Gsp) and antibiotics present in water bodies become organic pollutants that are harmful to human health and the ecological environment. Accurate and effective detection of these pollutants has far-reaching significance in many fields. A new three-dimensional metal-organic framework (MOF), {[Eu3(L)2(HCOO-)(H2O)3]·2H2O·2DMF}n (Eu-MOF), was synthesized from 3,5-bis(2,4-dicarboxylphenyl)nitrobenzene (H4L) ligand and Eu3+ via the solvothermal method in this paper. The Eu-MOF demonstrates strong red fluorescence and can remain stable in different pH solutions. The MOF fluorescence probe could detect organic pollutants through the "shut-off" effect, with a fast response speed and a low detection limit [Gsp, nitrofurantoin (NFT), and nitrofurazone (NFZ) for 0.43, 0.38, and 0.41 µM, respectively]. During the testing process, Eu-MOF exhibited good selectivity and recoverability. Furthermore, the mechanism of fluorescence quenching was investigated, and the recoveries were also good in real samples. This paper introduced a deep learning model to recognize the fluorescence images, a portable intelligent logic detector designed for real-time detection of Gsp by logic gate strategy, and an anticounterfeiting mark prepared based on inkjet printing. Importantly, this work provides a new way of thinking for the detection of organic pollutants in water with high sensitivity and practicality by combining the fluorescence probe with machine learning and logical judgment.


Assuntos
Antibacterianos , Európio , Corantes Fluorescentes , Gossipol , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Európio/química , Antibacterianos/análise , Antibacterianos/química , Gossipol/análise , Gossipol/química , Poluentes Químicos da Água/análise , Nitrofuranos/análise , Espectrometria de Fluorescência , Estrutura Molecular , Limite de Detecção
5.
Molecules ; 29(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39064943

RESUMO

A series of 13 new 3-substituted 5-(5-nitro-2-furyl)-1,2,4-oxadiazoles was synthesized from different aminonitriles. All compounds were screened in the disc diffusion test at a 100 µg/mL concentration to determine the bacterial growth inhibition zone presence and diameter, and then the minimum inhibitory concentrations (MICs) were determined for the most active compounds by serial dilution. The compounds showed antibacterial activity against ESKAPE bacteria, predominantly suppressing the growth of 5 species out of the panel. Some compounds had similar or lower MICs against ESKAPE pathogens compared to ciprofloxacin, nitrofurantoin, and furazidin. In particular, 3-azetidin-3-yl-5-(5-nitro-2-furyl)-1,2,4-oxadiazole (2h) inhibited S. aureus at a concentration lower than all comparators. Compound 2e (5-(5-nitro-2-furyl)-3-[4-(pyrrolidin-3-yloxy)phenyl]-1,2,4-oxadiazole) was active against Gram-positive ESKAPE pathogens as well as M. tuberculosis. Differences in the molecular periphery led to high selectivity for the compounds. The induced-fit docking (IFD) modeling technique was applied to in silico research. Molecular docking results indicated the targeting of compounds against various nitrofuran-associated biological targets.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Nitrofuranos , Nitrofuranos/farmacologia , Nitrofuranos/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Desenho de Fármacos , Relação Estrutura-Atividade , Oxidiazóis/química , Oxidiazóis/farmacologia , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124836, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39032236

RESUMO

Nitrofuran antibiotics (NFAs) residues in waterare a persistent concern for the public due to the potential threats they pose to human health and the environment. Therefore, efficient probes that are capable of detecting trace amounts of antibiotics in real water environments have become a top priority. Herein, a novel fluorescent Zn-MOF probe (MOF-1) was revealed for the highly selective and sensitive sensing of NFAs. MOF-1 was rationally constructed with Zn(NO3)2·6H2O, 5,5'-(anthracene-9,10-diyl) diisophthalic acid (H4ADIP) and 1,3-bis(imidazol-1-ylmethyl)-benzene (mbib) by using the solvothermal method. Fluorescence sensing experiments demonstrate that MOF-1 can function as a fluorescent sensor for selective, sensitive, and rapid detection of NFAs among 15 antibiotics including ciprofloxacin (CPFX), chloramphenicol (CAP), sulfonamides and NFAs. Fluorescence titration experiments indicated that MOF-1 exhibited remarkably low detection limits of 0.19 µM, 0.26 µM, and 0.34 µM for furazolidone (FZD), furaltadone (FDH) and nitrofurazone (NFZ), respectively. Meanwhile, MOF-1 was successfully employed for NFAs detection in real samples with the recoveries of 98.7 % - 104.1 %, and a relative standard deviation below 5.1 %. Moreover, the sensing mechanism could be ascribed to the synergistic effect between the internal filtering effect and photoinduced electron transfer according to the experiment results and DFT calculations. Additionally, test strips were prepared based on MOF-1 for point of care testing of NFAs.


Assuntos
Antibacterianos , Corantes Fluorescentes , Estruturas Metalorgânicas , Nitrofuranos , Espectrometria de Fluorescência , Zinco , Nitrofuranos/análise , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Antibacterianos/análise , Antibacterianos/síntese química , Antibacterianos/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Zinco/análise , Zinco/química , Limite de Detecção
7.
Food Chem ; 459: 140445, 2024 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-39024887

RESUMO

The misuse of antibiotics has caused serious impacts on food safety and human health, making it crucial to develop rapidly and highly sensitive methods for detecting trace nitrofuran antibiotics (NFs). In this study, phosphorus, nitride-doped carbon nanosheets (PN/CNs) were synthesized using a simple hydrothermal method based on graphitic carbon nitride. This prepared material showed excellent water solubility and stable optical properties. A new fluorescence sensing platform based on PN/CNs was constructed for the highly sensitive detection of four NFs. This sensitivity was mainly attributed to the fluorescence resonance energy transfer (FRET) mechanism. The limits of detection for nitrofurazone, nitrofurantoin, furazolidone and furaltadone were determined to be 13.41, 15.24, 16.37 and 19.94 nM, respectively. The high sensitivity and selectivity of PN/CNs for these four NFs were thoroughly evaluated by the Stern-Volmer equation and FRET quenching efficiency. This proposed method exhibited high sensitivity and can be successfully applied to detect NFs in fish.


Assuntos
Antibacterianos , Peixes , Transferência Ressonante de Energia de Fluorescência , Contaminação de Alimentos , Nanoestruturas , Nitrofuranos , Nitrofuranos/análise , Antibacterianos/análise , Antibacterianos/química , Animais , Nanoestruturas/química , Contaminação de Alimentos/análise , Carbono/química , Limite de Detecção , Fluorescência , Fósforo/química , Fósforo/análise , Alimentos Marinhos/análise
8.
Inorg Chem ; 63(20): 9058-9065, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38720438

RESUMO

Nitrofurans are important synthetic broad-spectrum antibacterial drugs with the basic structure of 5-nitrofuran. Due to their toxicity, it is essential to develop a sensitive sensor with strong anti-interference capabilities for their detection. In this work, two {P4Mo6O31}12--based compounds, [H4(HPTTP)]2{CuI[Mo12O24(OH)6(PO4)3(HPO4)(H2PO4)4]}·xH2O (x = 13 for (1), 7 for (2); HPTTP = 4,4',4″,4‴-(1H-pyrrole-2,3,4,5-tetrayl)tetrapyridine), exhibiting similar coordination but distinct stacking modes. Both compounds were synthesized and used for the electrochemical detection of nitrofuran antibiotics. The tetrapyridine-based ligand was generated in situ during assembly, and its potential mechanism was discussed. Composite electrode materials, formed by mixing graphite powder with compounds 1-2 and physically grinding them, proved to be highly effective in the electrochemical trace detection of furazolidone (FZD) and furaltadone hydrochloride (FTD·HCl) under optimal conditions. Besides, the possible electrochemical detection mechanisms of two nitro-antibiotics were studied.


Assuntos
Antibacterianos , Complexos de Coordenação , Cobre , Nitrofuranos , Polímeros , Antibacterianos/química , Antibacterianos/análise , Ligantes , Nitrofuranos/análise , Nitrofuranos/química , Cobre/química , Cobre/análise , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Polímeros/química , Molibdênio/química , Piridinas/química , Estrutura Molecular , Técnicas Eletroquímicas , Modelos Moleculares
9.
Chem Asian J ; 19(15): e202400377, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38758347

RESUMO

The monitoring and precise determination of pesticides and pharmaceutical drugs and their residues have become increasingly important in the field of food safety and water contamination issues. Herein, a fluorescent aluminium MOF-based sensor (1) was developed for the selective recognition of neonicotinoid insecticide dinotefuran and anti-Parkinson's drug entacapone. Guest-free MOF 1' exhibited ultra-fast response (<5 s) and ultra-low detection limits of 2.3 and 7.6 nM for dinotefuran and entacapone, which are lower than the previously reported MOF-based sensors. In the presence of other competitive analytes, great selectivity was achieved towards both analytes. The probe was recyclable up to five cycles. The sensing ability was explored towards entacapone in human serum, urine and dinotefuran in real soil, rice, honey samples, different fruits, vegetables, real water specimens and a wide range of pH media. A low-cost, handy MOF-based polymer thin-film composite (1'@PVDF-PVP) was developed for the on-site detection of dinotefuran and entacapone. Mechanistic studies involving analytical techniques and theoretical calculations suggested that FRET and PET are the probable reasons for entacapone sensing whereas IFE is responsible for dinotefuran detection. The entire work presents a low cost, multi-use photoluminescent sensor of entacapone and dinotefuran to address the environmental pollution.


Assuntos
Guanidinas , Inseticidas , Estruturas Metalorgânicas , Neonicotinoides , Nitrilas , Neonicotinoides/análise , Neonicotinoides/urina , Estruturas Metalorgânicas/química , Humanos , Inseticidas/análise , Inseticidas/sangue , Nitrilas/química , Guanidinas/análise , Guanidinas/química , Guanidinas/sangue , Nitrofuranos/análise , Antiparkinsonianos/análise , Antiparkinsonianos/sangue , Corantes Fluorescentes/química , Estrutura Molecular , Limite de Detecção , Nitrocompostos
10.
Molecules ; 29(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38675539

RESUMO

Nitrofuran (NF) contamination in food products is a global problem resulting in the banned utilization and importation of nitrofuran contaminated products. A novel chromogenic detection method using a specific DNA aptamer with high affinity and specificity to nitrofurans was developed. Single-stranded DNA aptamers specific to nitrofuran metabolites, including 3-amino-2-oxazolidinone (AOZ), 3-amino-5-methylmorpholino-2-oxazolidinone (AMOZ), and 1-aminohydantoin (AHD), were isolated using magnetic bead-SELEX. The colorimetric detection of nitrofurans using gold nanoparticles (AuNPs) exhibited an AOZ detection range of 0.01-0.06 ppb with a limit of detection (LOD) of 0.03 ppb. At the same time, this system could detect AMOZ and AHD at a range of 0.06 ppb and 10 ppb, respectively. The fast nitrofuran extraction method was optimized for food, such as fish tissues and honey, adjusted to be completed within 3-6 h. This novel apta-chromogenic detection method could detect NF metabolites with a sensitivity below the minimum required performance limit (MPRL). This analysis will be valuable for screening, with a shortened time of detection for aquaculture products such as shrimp and fish muscle tissues.


Assuntos
Aptâmeros de Nucleotídeos , Contaminação de Alimentos , Nanopartículas Metálicas , Nitrofuranos , Nitrofuranos/análise , Nitrofuranos/metabolismo , Nanopartículas Metálicas/química , Contaminação de Alimentos/análise , Aptâmeros de Nucleotídeos/química , Oxazolidinonas/análise , Oxazolidinonas/metabolismo , Ouro/química , Limite de Detecção , Hidantoínas/análise , Animais , Mel/análise , Colorimetria/métodos , Análise de Alimentos/métodos
11.
Biomed Pharmacother ; 174: 116459, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518599

RESUMO

Ubiquitin-specific protease (USP), an enzyme catalyzing protein deubiquitination, is involved in biological processes related to metabolic disorders and cancer proliferation. We focused on constructing predictive models tailored to unveil compounds boasting USP21 inhibitory attributes. Six models, Extra Trees Classifier, Random Forest Classifier, LightGBM Classifier, XGBoost Classifier, Bagging Classifier, and a convolutional neural network harnessed from empirical data were selected for the screening process. These models guided our selection of 26 compounds from the FDA-approved drug library for further evaluation. Notably, nifuroxazide emerged as the most potent inhibitor, with a half-maximal inhibitory concentration of 14.9 ± 1.63 µM. The stability of protein-ligand complexes was confirmed using molecular modeling. Furthermore, nifuroxazide treatment of HepG2 cells not only inhibited USP21 and its established substrate ACLY but also elevated p-AMPKα, a downstream functional target of USP21. Intriguingly, we unveiled the previously unknown capacity of nifuroxazide to increase the levels of miR-4458, which was identified as downregulating USP21. This discovery was substantiated by manipulating miR-4458 levels in HepG2 cells, resulting in corresponding changes in USP21 protein levels in line with its predicted interaction with ACLY. Lastly, we confirmed the in vivo efficacy of nifuroxazide in inhibiting USP21 in mice livers, observing concurrent alterations in ACLY and p-AMPKα levels. Collectively, our study establishes nifuroxazide as a promising USP21 inhibitor with potential implications for addressing metabolic disorders and cancer proliferation. This multidimensional investigation sheds light on the intricate regulatory mechanisms involving USP21 and its downstream effects, paving the way for further exploration and therapeutic development.


Assuntos
Reposicionamento de Medicamentos , Hidroxibenzoatos , Aprendizado de Máquina , Nitrofuranos , Humanos , Nitrofuranos/farmacologia , Animais , Reposicionamento de Medicamentos/métodos , Células Hep G2 , Hidroxibenzoatos/farmacologia , Camundongos , Ubiquitina Tiolesterase/antagonistas & inibidores , Ubiquitina Tiolesterase/metabolismo
12.
Elife ; 122024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441416

RESUMO

Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosis in vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nitrofuranos , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Antígeno B7-H1 , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Hidroxibenzoatos
13.
Sci Total Environ ; 919: 170848, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38340835

RESUMO

Furaltadone (FTD) is an antibiotic belonging to the nitrofurans group. It has been broadly used in livestock and aquaculture for therapeutic purposes, as well as for stimulating promotion. Although the European Union has imposed restrictions on the use of FTD since 1995 due to concerns regarding its toxicity, in many cases FTD has been excessively and/or illegally applied in productive animals in developing countries, because of its high efficacy and low-cost. Unlike other nitrofuran compounds, the hydrolytic and photolytic behavior of FTD in natural aquatic systems has not been thoroughly investigated. To this end, hydrolysis in different pH values and photolysis in aquatic environment, including lake, river and sea water have been both examined. Hydrolysis was found to have an insignificant impact on degradation of FTD in the aquatic environment relevant pH values, whereas indirect photolysis proved to be the main route of its elimination. The identification of tentative photoproducts (PPs) was performed using ultra high performance liquid chromatography coupled to hybrid LTQ/Orbitrap high resolution mass spectrometry. A possible pathway for photolytic transformation of FTD was proposed. Additionally, in silico simulations were used to evaluate the toxicity such as the mutagenicity of FTD and PPs. Complementary to the low-cost and time-limited simulations, an in vitro method (Vibrio Fischeri bioluminescence) was also used to assess ecotoxicity.


Assuntos
Demência Frontotemporal , Nitrofuranos , Oxazolidinonas , Poluentes Químicos da Água , Animais , Espectrometria de Massas , Nitrofuranos/análise , Nitrofuranos/química , Água/química , Fotólise , Poluentes Químicos da Água/análise , Cinética
14.
Biofactors ; 50(2): 360-370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37737462

RESUMO

The prevalence of diabetes mellitus (DM) is alarmingly increasing worldwide. Diabetic retinopathy (DR) is a prevailing DM microvascular complication, representing the major cause of blindness in working-age population. Inflammation is a crucial player in DR pathogenesis. JAK/STAT3 axis is a pleotropic cascade that modulates diverse inflammatory events. Nifuroxazide (Nifu) is a commonly used oral antibiotic with reported JAK/STAT3 inhibition activity. The present study investigated the potential protective effect of Nifu against diabetes-induced retinal injury. Effect of Nifu on oxidative stress, JAK/STAT3 axis and downstream inflammatory mediators has been also studied. Diabetes was induced in Sprague Dawley rats by single intraperitoneal injection of streptozotocin (50 mg/kg). Animals were assigned into four groups: normal, Nifu control, DM, and DM + Nifu. Nifu was orally administrated at 25 mg/kg/day for 8 weeks. The effects of Nifu on oxidative stress, JAK/STAT3 axis proteins, inflammatory factors, tight junction proteins, histological, and ultrastructural alterations were evaluated using spectrophotometry, gene and protein analyses, and histological studies. Nifu administration to diabetic rats attenuated histopathological and signs of retinal injury. Additionally, Nifu attenuated retinal oxidative stress, inhibited JAK and STAT3 phosphorylation, augmented the expression of STAT3 signaling inhibitor SOCS3, dampened the expression of transcription factor of inflammation NF-κB, and inflammatory cytokine TNF-α. Collectively, the current study indicated that Nifu alleviated DR progression in diabetic rats, suggesting beneficial retino-protective effect. This can be attributed to blocking JAK/STAT3 axis in retinal tissues with subsequent amelioration of oxidative stress and inflammation.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Hidroxibenzoatos , Nitrofuranos , Animais , Ratos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/complicações , Nitrofuranos/farmacologia , Nitrofuranos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Janus Quinases/antagonistas & inibidores , Janus Quinases/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/efeitos dos fármacos
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123748, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38091651

RESUMO

Herein, blue-emitting gold nanoclusters (Au NCs) were carried out through tryptophan as the protecting and reducing agents. In aqueous solution of Au NCs@tryptophan, the addition of furaltadone guaranteed the interaction of furaltadone with tryptophan around Au NCs. The propinquity of furaltadone to Au NCs caused that the fluorescence of Au NCs was weakened by furaltadone based on the inner filter effect (IFE). Under the optimal measurement conditions, the logarithm of relative fluorescence intensity of Au NCs@tryptophan was linearly carried out with the furaltadone amount increasing from 0.5 to 100 µM, the corresponding detection limit was 0.087 µM. The fluorescence change of Au NCs@tryptophan displayed excellent selectivity and sensitivity for furaltadone than other possible substance in the human body. In view of Au NCs@tryptophan, the as-performed fluorescence nanosensor suggested outstanding ability for furaltadone sensing in real samples. Obviously, this nanoprobe of furaltadone could implement the naked-eye visual fluorescence determination of furaltadone.


Assuntos
Nanopartículas Metálicas , Nitrofuranos , Oxazolidinonas , Triptofano , Humanos , Espectrometria de Fluorescência/métodos , Ouro , Corantes Fluorescentes
16.
Int Immunopharmacol ; 127: 111298, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38070469

RESUMO

Methotrexate (MTX) has long manifested therapeutic efficacy in several neoplastic and autoimmune disorders. However, MTX-associated intestinal toxicity restricts the continuation of treatment. Nifuroxazide (NIF) is an oral antibiotic approved for gastrointestinal infections as an effective antidiarrheal agent with a high safety profile. The current study was designed to explore the potential efficacy of NIF in alleviating intestinal toxicity associated with MTX chemotherapy with the elucidation of the proposed molecular mechanisms. Rats were administered NIF (50 mg/kg; p.o.) for ten days. On day five, a single i.p. injection of MTX (20 mg/kg) was given to induce intestinal intoxication. At the end of the experiment, duodenal tissue samples were isolated for biochemical, Western blotting, immunohistochemical (IHC), and histopathological analysis via H&E, PSA, and Alcian blue stains. NIF showed antioxidant enteroprotective effects against MTX intestinal intoxication through enhanced expression of the redox-sensitive signals of PPAR-γ, SIRT1, and Nrf2 estimated by IHC. Moreover, NIF down-regulated the pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6), NF-κB protein expression, and the phosphorylation of JAK1/STAT3 proteins, leading to mitigation of intestinal inflammation. In accordance, the histological investigation revealed that NIF ameliorated the intestinal pathological changes, preserved the goblet cells, and reduced the inflammatory cells infiltration. Therefore, NIF could be a promising candidate for adjunctive therapy with MTX to mitigate the associated intestinal injury and increase its tolerability.


Assuntos
Hidroxibenzoatos , Metotrexato , NF-kappa B , Nitrofuranos , Ratos , Animais , NF-kappa B/metabolismo , Metotrexato/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , PPAR gama/metabolismo , Sirtuína 1/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo
17.
Food Chem ; 438: 137961, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38011791

RESUMO

Antibiotic detection is crucial and challenging because the widespread consumption of antibiotics has shown extensive harmful effects on food, environment and human health. Here, we propose highly water-soluble and biocompatible hyaluronic acid (HYA) functionalized upconversion nanoparticles (UCNPs) for ratiometric detection of multiple antibiotics. The ultraviolet upconversion luminescence (UCL) from UCNPs was significantly quenched by nitrofurazone (NFZ)/nitrofurantoin (NFT), and blue UCL was quenched by doxorubicin (DOX), while red UCL remained unchanged for internal reference. The UCNPs-HYA nanoprobes exhibit excellently sensitive and selective NFZ, NFT and DOX detection in linear range of 2.5-100 µM, 2.5-80 µM, and 2.5-200 µM with the LOD at 0.28 µM (55 µg/kg), 0.20 µM (48 µg/kg) and 0.17 µM (97 µg/kg), respectively. The nanoprobes achieved detecting real samples of NFZ in lake water, liquid milk and chicken meat with satisfactory results, and UCL bioimaging of DOX in HeLa cells. The UCNPs-HYA ratiometric nanoprobes are promising for food samples detection and potential biosensing in the cellular environment.


Assuntos
Nanopartículas , Nitrofuranos , Humanos , Células HeLa , Ácido Hialurônico , Água , Doxorrubicina , Antibacterianos
18.
J Pharm Biomed Anal ; 239: 115878, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38039869

RESUMO

Despite nifurtimox (NFX) being a traditional drug for treating Chagas disease, some of its physicochemical properties are still unknown, especially its thermal behavior, which brings important outcomes regarding stability and compatibility. In this work, a comprehensive study of NFX's thermal properties was conducted to assist incremental innovations that can improve the efficacy of this drug in novel pharmaceutical products. For this purpose, thermal analyses associated with spectroscopy and spectrometry techniques were used. DSC analyses revealed that the melt crystallization of the NFX led to its amorphous form with the possible formation of a minor fraction of a different crystalline phase. Coats-Redfern method using TGA results indicated the activation energy of NFX non-isothermal degradation as 348.8 ± 8.2 kJ mol-1, which coincides with the C-NO2 bond dissociation energy of the 2-nitrofuran. Investigation of the isothermal degradation kinetics using FTIR 2D COS showed the possible detachment of radical NO2 and ethylene from the NFX structure, which could affect its mechanism of action. A preliminary mechanism for the thermal degradation of this drug was also proposed. The results enhanced the understanding of NFX's thermal properties, providing valuable insights, especially for developing NFX-based pharmaceutical products that involve thermal processing.


Assuntos
Nifurtimox , Nitrofuranos , Nifurtimox/metabolismo , Nifurtimox/uso terapêutico , Cristalização , Dióxido de Nitrogênio , Preparações Farmacêuticas
19.
Food Chem ; 439: 138171, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38100875

RESUMO

Nitrofuran (NF) antibiotics have been banned worldwide in aquaculture due to their potential carcinogenicity and mutagenicity. Because of the short half-life of NF antibiotics, an easy and sensitive multiple lateral flow immunoassay (mLFIA) based on europium nanoparticles (EuNPs) has been successfully established to simultaneously and quantitatively detect 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), 3-amino-2-oxazolidinone (AOZ) and sodium nifurstylenate (NFS) in aquatic products. The EuNP-mLFIA assay was accomplished within 10 min. The limits of detection (LODs) for AOZ, AMOZ and NFS were 0.013, 0.019 and 0.023 ng/mL, respectively. The average recoveries of AOZ, AMOZ and NFS were 98.0-104.4%, 96.0-102.6% and 98.0-102.8%, respectively. It showed satisfactory consistency, and the feasibility was validated by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Briefly, this method will become a powerful tool for monitoring multiple NF antibiotics and provide promising applications in the field of food safety and environmental testing.


Assuntos
Nanopartículas Metálicas , Nitrofuranos , Antibacterianos/análise , Európio , Espectrometria de Massas em Tandem/métodos , Nitrofuranos/análise , Imunoensaio
20.
Molecules ; 28(17)2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37687103

RESUMO

Developing efficient and sensitive MOF-based luminescence sensors for bioactive molecule detection is of great significance and remains a challenge. Benefiting from favorable chemical and thermal stability, as well as excellent luminescence performance, a porous Zn(II)Ho(III) heterometallic-organic framework (ZnHoMOF) was selected here as a bifunctional luminescence sensor for the early diagnosis of a toluene exposure biomarker of hippuric acid (HA) through "turn-on" luminescence enhancing response and the daily monitoring of NFT/NFZ antibiotics through "turn-off" quenching effects in aqueous media with high sensitivity, acceptable selectivity, good anti-interference, exceptional recyclability performance, and low detection limits (LODs) of 0.7 ppm for HA, 0.04 ppm for NFT, and 0.05 ppm for NFZ. Moreover, the developed sensor was employed to quantify HA in diluted urine samples and NFT/NFZ in natural river water with satisfactory results. In addition, the sensing mechanisms of ZnHoMOF as a dual-response chemosensor in efficient detection of HA and NFT/NFZ antibiotics were conducted from the view of photo-induced electron transfer (PET), as well as inner filter effects (IFEs), with the help of time-dependent density functional theory (TD-DFT) and spectral overlap experiments.


Assuntos
Antibacterianos , Nitrofuranos , Luminescência , Biomarcadores
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