RESUMEN
Deoxynivalenol (DON) is universally detected trichothecene in most cereal commodities, which is considered as a major hazardous material for human and animal health. Intestine is the most vulnerable organ with higher concentration of DON than other organs, owing to the first defense barrier function to exogenous substances. However, the underling mechanisms about DON-induced intestinal toxicity remain poorly understood. Here, DON poisoning models of IPEC-J2 cells was established to explore adverse effect and the potential mechanism of DON-induced enterotoxicity. Results showed that DON exposure destroyed IPEC-J2 cells morphology. Results showed that DON exposure destroyed IPEC-J2 cells morphology. Intestinal epithelial barrier injury was caused by DON with increasing LDH release, decreasing cell viability as well decreasing tight junction protein expressions (Occludin, N-Cad, ZO-1, Claudin-1 and Claudin-3). Moreover, DON caused mitochondrial dysfunction by opening mitochondrial permeability transition pore and eliminating mitochondrial membrane potential. DON exposure upregulated protein and mRNA expression of mitochondrial fission factors (Drp1, Fis1, MIEF1 and MFF) and mitophagy factors (PINK1, Parkin and LC3), downregulated mitochondrial fusion factors (Mfn1, Mfn2, except OPA1), resulting in mitochondrial dynamics imbalance and mitophagy. Overall, these findings suggested that DON induced tight junction dysfunction in IPEC-J2 cells was related to mitochondrial dynamics-mediated mitophagy.
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Dinámicas Mitocondriales , Mitofagia , Humanos , Porcinos , Animales , Uniones Estrechas , Ocludina , Factores de Elongación de Péptidos , Proteínas MitocondrialesRESUMEN
The presence of anorexia in animals is the most well-known clinical symptom of T-2 toxin poisoning. T-2 toxin is the most characteristic type A toxin in the trichothecene mycotoxins. The consumption of T-2 toxin can cause anorexic response in mice, rats, rabbits, and other animals. In this review, the basic information of T-2 toxin, appetite regulation mechanism and the molecular mechanism of T-2 toxin-induced anorectic response in animals are presented and discussed. The objective of this overview is to describe the research progress of anorexia in animals produced by T-2 toxin. T-2 toxin mainly causes antifeedant reaction through four pathways: vagus nerve, gastrointestinal hormone, neurotransmitter and cytokine. This review aims to give an academic basis and useable reference for the prevention and treatment of clinical symptoms of anorexia in animals resulting from T-2 toxin.
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Depresores del Apetito , Micotoxinas , Toxina T-2 , Ratones , Ratas , Animales , Conejos , Anorexia/inducido químicamente , Micotoxinas/efectos adversos , NeurotransmisoresRESUMEN
AIMS: The purpose of this paper is to prospectively evaluate the performance of an artificial intelligence (AI) system in diagnosing thyroid nodules and to assess its potential value in comparison with the performance of radiologists with different levels of experience, as well as the factors affecting its diagnostic accuracy. BACKGROUND: In recent years, medical imaging diagnosis using AI has become a popular topic in clinical application research. OBJECTIVE: This study aimed to evaluate the performance of an AI system in diagnosing thyroid nodules and compare it with the performance levels of different radiologists. METHODS: This study involved 426 patients screened for thyroid nodules at the First Affiliated Hospital of Guangzhou Medical University between July 2017 and March 2019. All of the nodules were evaluated by radiologists with various levels of experience and an AI system. The diagnostic performances of two junior and two senior radiologists, an AI system, and an AI-assisted junior radiologist were compared, as were their diagnostic results with respect to nodules of different sizes. RESULTS: The senior radiologists, the AI system, and the AI-assisted junior radiologist performed better than the junior radiologist (p < 0.05). The area under the curves of the AI system and the AI-assisted junior radiologist were similar to the curve of the senior radiologists (p > 0.05). The diagnostic results concerning the two nodule sizes showed that the diagnostic error rates of the AI system, junior radiologists, and senior radiologists for nodules with a maximum diameter of ≤1 cm (Dmax ≤ 1 cm) were higher than those for nodules with a maximum diameter of 1 cm (Dmax > 1 cm) (23.4% vs. 12.1%, p = 0.002; 26.6% vs. 7.3%, p < 0.001; and 38.3% vs. 14.6%, p < 0.001). CONCLUSION: The AI system is a decision-making tool that could potentially improve the diagnostic efficiency of junior radiologists. Micronodules with Dmax ≤ 1cm were significantly correlated with diagnostic accuracy; accordingly, more micronodules of this size, in particular, should be added to the AI system as training samples. Other: The system could be a potential decision-making tool for effectively improving the diagnostic efficiency of junior radiologists in the community.
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Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Inteligencia Artificial , Curva ROC , Ultrasonografía/métodos , RadiólogosRESUMEN
Objective: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated. Methods: In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants. Results: We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations. Conclusion: These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.
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COVID-19 , SARS-CoV-2 , Aminoácidos , COVID-19/epidemiología , Genómica , Humanos , Mutación , Filogenia , SARS-CoV-2/genéticaRESUMEN
OBJECTIVE: To study PD-1 and PD-L1 expressions during 24 weeks telbivudine antiviral treatment in patients with chronic hepatitis B (CHB) and to explore the relationship between PD-1 expression and HBeAg/HBeAb seroconversion. METHODS: Ten CHB cases with HLA-A2 and HBeAg positive were treated with telbivudine 600 mg/d orally for 24 weeks. Fresh blood samples were collected at week 0, 12 and 24 after treatment. HBV-specific CD8+ T cells were expanded in vitro. Cell culture medium were collected for interferon gamma (IFNgamma) detection. Flow cytometry was used to detect the HLA-A type, PD-1, PD-L1 and HBV specific CD8+ T cells. The expressions of PD-1 and PD-L1, the counts of HBV-specific CD8+ T cells in circulating CD8+ lymphocytes, and IFNgamma concentration in culture medium were evaluated during antiviral treatment. RESULTS: At week 0, 12 and 24 after telbivudine treatment, 7 of 10 patients were HBV DNA undetectable, 2 were HBeAg seroconversion and 2 were HBeAg lose but anti-HBe negative. The frequency of PD-1-positive PBMCs were 52.1%+/-17.0%, 39.1%+/-18.2% and 23.4%+/-16.3% (week 24 vs week 0, P < 0.01) respectively; PD-L1 positive PBMCs were 45.6%+/-15.4%, 34.6%+/-16.2% and 20.9%+/-9.5% respectively(week 24 vs week 0, P < 0.01; week 24 vs week 12, P < 0.05). The frequency of PD-1-positive CD8+ T cells were 76.2%+/-10.4%, 66.5%+/-15.4% and 49.5%+/-25.3% respectively (week 24 vs week 0, P < 0.01; week 12 vs week 0, P < 0.05; week 24 vs week 12, P < 0.05); HBV-specific CD8 cells were 1.3%+/-0.5%, 1.5%+/-1.0% and 2.2%+/-1.5%; IFNgamma levels in cell culture medium were (91.7+/-82.1) pg/ml, (99.4+/-93.5) pg/ml and (109.5+/-86.6) pg/ml. A remarkable decrease of PD-1 and PD-L1 expressions and increase of HBV-specific CD8+ T cells were observed in patients who had HBeAg/HBeAb seroconversion at week 24. CONCLUSIONS: Direct suppression of HBV replication by telbivudine in CHB patients can decrease PD-1 and PD-L1 expressions and restore HBV-specific CD8+T cells. The relationship between the changes of PD-1 expression and HBeAg/HBeAb seroconversion during antiviral therapy in HBeAg-positive patients need to confirm by future study.
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Antígeno B7-H1/metabolismo , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Adulto , Antivirales/uso terapéutico , Linfocitos T CD8-positivos/inmunología , Femenino , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Humanos , Masculino , Nucleósidos/uso terapéutico , Pirimidinonas/uso terapéutico , Telbivudina , Timidina/análogos & derivados , Adulto JovenRESUMEN
The synthesis and spectral properties of a chemidosimeter 1,4-di[2-(6-ethylamino-3-ethylimino-2,7-dimethyl-3H-xanthen-9-yl) benzoic acid (aminomethyl)-3-phenylthiourea] benzene (1) for Hg(II) ions are reported, and it has been demonstrated that 1 can be used as a fluorescent probe for monitoring Hg(II) ions in living cells.
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Células/química , Células/citología , Contaminantes Ambientales/análisis , Colorantes Fluorescentes/química , Mercurio/análisis , Rodaminas/química , Urea/análogos & derivados , Supervivencia Celular , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , Temperatura , Urea/químicaRESUMEN
The interaction of 1-phenyl-3-(coumarin-6-yl)sulfonylurea (SU22) with bovine serum albumin (BSA) has been investigated by fluorescence quenching spectroscopy combined with UV-absorption, circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy techniques under simulative physiological conditions for the first time. Fluorescence data and UV-absorption spectra revealed that the quenching mechanism of fluorescence of BSA by SU22 was a static quenching process and the number of binding sites was about 0.8858; the thermodynamic parameters (DeltaG=-29.23 kJ mol(-1), DeltaH=-47.48 kJ mol(-1), and DeltaS=-61.24 J mol(-1)K(-1)) explained that hydrogen bond and Van der Waals interaction were the main binding force stabilizing the complex. The binding average distance between SU22 and BSA was obtained (3.20 nm) on the basis of the Förster's theory. In addition, The CD spectra and FT-IR spectra have proved that BSA secondary structure changed in the presence of SU22 in aqueous solution.
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Cumarinas/química , Cumarinas/metabolismo , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo , Compuestos de Sulfonilurea/química , Compuestos de Sulfonilurea/metabolismo , Animales , Bovinos , Dicroismo Circular , Cumarinas/síntesis química , Estructura Secundaria de Proteína , Espectroscopía Infrarroja por Transformada de Fourier , TermodinámicaRESUMEN
The binding properties on [PrL2(NO3)](NO3)2 (L=9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperaziny)-7-oxo-7Hpyrido[1,2,3-de]-1,4-benzoxazine-6-carbaldehyde benzoyl hydrazone) to bovine serum albumin (BSA) have been studied for the first time using fluorescence spectroscopy in combination with UV-Vis absorbance spectroscopy. The results showed that [PrL2(NO3)](NO3)2 strongly quenched the intrinsic fluorescence of BSA through a static quenching procedure, and non-radiation energy transfer happened within molecules. The number of binding site was about 1, and the efficiency of Förster energy transfer provided a distance of 4.26 nm between tryptophan and [PrL2(NO3)](NO3)2 binding site. At 288, 298, 310 K, the quenching constants of BSA-[PrL2(NO3)](NO3)2 system were 5.11×10(4), 4.33×10(4) and 3.71×10(4) l M(-1). ΔH, ΔS and ΔG were obtained based on the quenching constants and thermodynamic theory (ΔH<0, ΔS>0 and ΔG<0). These results indicated that hydrophobic and electrostatic interactions are the mainly binding forces in the [PrL2(NO3)](NO3)2-BSA system. In addition, the CD spectra have proved that BSA secondary structure changed in the presence of [PrL2(NO3)](NO3)2 in aqueous solution. Moreover, the interaction between [PrL2(NO3)](NO3)2 and calf thymus DNA (CT DNA) was studied by spectroscopy and viscosity measurements, which showed that the binding mode of the [PrL2(NO3)](NO3)2 with DNA is intercalation. The DNA cleavage results show that in the absence of any reducing agent, the [PrL2(NO3)](NO3)2 can cleave plasmid pBR322 DNA and its hydrolytic mechanism was demonstrated with hydroxyl radical scavengers and singlet oxygen quenchers.
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ADN/metabolismo , Ofloxacino/metabolismo , Praseodimio/metabolismo , Albúmina Sérica Bovina/metabolismo , Animales , Sitios de Unión , Bovinos , Electrones , Transferencia de Energía , Etidio/química , Cinética , Ofloxacino/química , Yoduro de Potasio/química , Unión Proteica , Estructura Secundaria de Proteína , Sales (Química)/química , Albúmina Sérica Bovina/química , Espectrometría de Fluorescencia , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Volumetría , ViscosidadRESUMEN
Two novel copper(II) thiocyanate complexes with 4-(N,N-dimethylamino) pyridine and N,N-dimethylformamide (1) and with 4-(N,N-dimethylamino) pyridine (2) have been synthesized and characterized. The crystal and molecular structures of complexes 1 and 2 were determined by single-crystal X-ray diffraction. Antioxidative activity tests in vitro showed that complex 1 has significant antioxidative activity against hydroxyl free radicals from the Fenton reaction and also oxygen free radicals, which is better than standard antioxidants like vitamin C and mannitol. The interaction of complex 1 with calf thymus DNA was investigated by spectroscopic, cyclic voltammetry, and viscosity measurements. Results suggest that complex 1 can bind to DNA via partial intercalation mode. Moreover, complex 1 has been found to cleavage of plasmid DNA pBR322.
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Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/metabolismo , Complejos de Coordinación/farmacología , Cobre/química , División del ADN/efectos de los fármacos , ADN/metabolismo , Sitios de Unión/efectos de los fármacos , Cristalografía por Rayos X , ADN/biosíntesis , Dimetilformamida , Formamidas/química , Formamidas/metabolismo , Modelos Biológicos , Modelos Moleculares , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Compuestos Organometálicos/metabolismo , Compuestos Organometálicos/farmacología , Piridinas/química , Piridinas/metabolismo , Piridinas/farmacología , Tiocianatos/química , Tiocianatos/metabolismoRESUMEN
2-Phenylquinoline-4-carboylhydrazide (HL), and its novel nickel(II), zinc(II) complexes [M(HL)(2)(L)].2H(2)O.NO(3) (M=Ni (1), M=Zn (2)), have been synthesized and characterized by elemental analysis, molar conductivity, and IR spectra. The crystal structure of [Ni(HL)(2)(L)].2H(2)O.NO(3) obtained from ethanol solution was determined by X-ray diffraction analysis, crystallized in the rhombohedral system, space group R3 , Z=18, a=31.913(3)A, b=31.913(3)A, c=27.709(2)A, alpha=90 degrees , beta=90 degrees , gamma=120 degrees , R(1)=0.0647. The interactions of the complexes and the ligand with calf thymus DNA had been investigated using UV-Vis spectra, fluorescent spectra, CD (circular dichroism) spectra, CV (cyclic voltammetry) and viscosity measurements. These compounds were tested against MFC (mouse forestomach carcinoma) cell lines. The complex 1 showed significant cytotoxic activity against MFC cell lines. The cleavage reaction on plasmid DNA has been monitored by agarose gel electrophoresis. Results suggest that the two complexes bound to DNA via a groove binding mode and the complexes can cleave pBR322 DNA.
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Antineoplásicos/química , Hidrazinas/química , Níquel/química , Compuestos Organometálicos/química , Quinolinas/química , Zinc/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral , Cristalización , Cristalografía por Rayos X , ADN/química , División del ADN , Diseño de Fármacos , Ligandos , Ratones , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/farmacología , Análisis EspectralRESUMEN
1-(4-aminoantipyrine)-3-tosylurea (H2L) and its three lanthanide (III) complexes, M(H2L)3 3NO3 [where M=Nd(III), Sm(III) and Eu(III)], have been synthesized and characterized. In addition, the DNA-binding properties of the three complexes have been investigated by UV-vis (ultraviolet and visible) absorption spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, cyclic voltammetry, and viscosity measurements. Results suggest that the three complexes bind to DNA via a groove binding mode. Furthermore, the antioxidant activity (superoxide and hydroxyl radical) of the metal complexes was determined by using spectrophotometer methods in vitro. These complexes were found to possess potent antioxidant activity and be better than standard antioxidants like vitamin C and mannitol.
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Antioxidantes/química , Antipirina/análogos & derivados , ADN/química , Metales de Tierras Raras/química , Compuestos Organometálicos/química , Urea/análogos & derivados , Antioxidantes/síntesis química , Antioxidantes/farmacología , Antipirina/química , Sitios de Unión , Dicroismo Circular , ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Electrodos , Radical Hidroxilo/química , Ligandos , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/farmacología , Espectrometría de Fluorescencia , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Relación Estructura-Actividad , Urea/química , ViscosidadRESUMEN
A new ligand, 1-cyclohexyl-3-tosylurea (H(2)L), was prepared by condensation ethyl N-(3-tossulfonyl) carbamate and cyclohexanamine. Its two lanthanide(III) complexes, Ln(H(2)L)(3) . 3NO(3) [Ln=Nd (1), and Eu (2)], have been synthesized and characterized on the base of element analyses, ESI-MS, molar conductivities, IR spectra and thermogravimetry/differential thermal analysis (TG-DTA). In addition, the DNA-binding properties of the ligand and its complexes have been investigated by electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroic (CD) spectroscopy and viscosity measurements. The experiment results suggest that the ligand and its two complexes bind to DNA via a groove binding mode, and the binding affinity of the complex 2 is higher than that of the complex 1 and the ligand. Furthermore, the antioxidant activity (superoxide and hydroxyl radical) of the ligand and its metal complexes was determined by using spectrophotometer methods in vitro. These complexes were found to possess potent antioxidant activity and be better than standard antioxidants like vitamin C and mannitol. In particular, complex 2 displayed excellent activity on the superoxide and hydroxyl radical.