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1.
Toxicol Appl Pharmacol ; 484: 116878, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38431229

RESUMEN

Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects. Febrifugine, identified as a quinazoline-type alkaloid compound extracted from the Cytidiaceae family plant Huangchangshan, exhibits heightened sensitivity to bladder cancer cells in comparison to control cells (non-cancer cells) group. The proliferation growth of bladder cancer cells T24 and SW780 was effectively inhibited by Febrifugine, and the IC50 was 0.02 and 0.018 µM respectively. Febrifugine inhibits cell proliferation by suppressing DNA synthesis and induces cell death by reducing steroidogenesis and promoting apoptosis. Combined with transcriptome analysis, Febrifugine was found to downregulate low density lipoprotein receptor-associated protein, lanosterol synthase, cholesterol biosynthesis second rate-limiting enzyme, 7-dehydrocholesterol reductase, flavin adenine dinucleotide dependent oxidoreductase and other factors to inhibit the production of intracellular steroids in bladder cancer T24 cells. The results of animal experiments showed that Febrifugine could inhibit tumor growth. In summary, the effect of Febrifugine on bladder cancer is mainly through reducing steroid production and apoptosis. Therefore, this study contributes to the elucidation of Febrifugine's potential as an inhibitor of bladder cancer and establishes a solid foundation for the future development of novel therapeutic agents targeting bladder cancer.


Asunto(s)
Piperidinas , Neoplasias de la Vejiga Urinaria , Animales , Línea Celular Tumoral , Proliferación Celular , Neoplasias de la Vejiga Urinaria/patología , Quinazolinas/farmacología , Quinazolinas/uso terapéutico , Apoptosis
2.
Chem Biodivers ; 21(6): e202400583, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38590217

RESUMEN

Plant disease control mainly relies on pesticides. In this study, a series of coumarin derivatives containing hydrazone moiety were designed and synthesized. The synthesized compounds were characterized and used to evaluate the antifungal activity against four pathogens, Botrytis cinerea, Alternaria solani, Fusarium oxysporum, and Alternaria alternata. The results showed that the inhibition rate of some compounds at 100 µg/mL in 96 hours reached around 70 % against A. alternata, higher than that of the positive control. The corresponding EC50 values were found at around 30 µg/mL. Finally, the compound 3 b was screened out with the lowest EC50 value (19.49 µg/mL). The analysis of SEM and TEM confirmed that the compound 3 b can obviously damage the morphological structure of hyphae, resulting in the depletion of the cells by the destruction of morphological matrix and leakage of contents. RNA sequencing showed that compounds 3 b mainly affected the pentose phosphate pathway, which caused to destroy the layer of mitochondrial structure. Molecular docking showed that compounds 3 b fitted the binding pocket of yeast transketolase and interacted with lysine at the hydrazone structure. Our results suggested that the introduction of hydrazone was an effective strategy for the design of novel bioactive compounds.


Asunto(s)
Alternaria , Antifúngicos , Botrytis , Cumarinas , Fusarium , Hidrazonas , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Hidrazonas/química , Hidrazonas/farmacología , Hidrazonas/síntesis química , Cumarinas/química , Cumarinas/farmacología , Cumarinas/síntesis química , Alternaria/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Fusarium/efectos de los fármacos , Relación Estructura-Actividad , Botrytis/efectos de los fármacos , Estructura Molecular , Relación Dosis-Respuesta a Droga
3.
Chem Biodivers ; 21(5): e202400311, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38494946

RESUMEN

Phytopathogenic fungi is the most devastating reason for the decrease of the agricultural production and food safety. To develop new fungicidal agents for resistance concerning, a novel series of aminocoumarin derivatives were synthesized and their fungicidal activity were investigated both in vitro and in vivo. Transmission electron microscope (TEM), scanning electron microscope (SEM), RNA-Seq, 3D-QSAR and molecular docking were applied to reveal the underlying anti-fungal mechanisms. Most of the compounds exhibited significant fungicidal activity. Notably, compound 10c had a more extensive fungicidal effect than positive control. TEM indicated that compound 10c could cause abnormal morphology of cell walls, vacuoles and release of cellular contents. Transcriptional analysis data indicated that 895 and 653 out of 1548 differential expressed genes (DEGs) were up-regulated and down-regulated respectively. The Go and KEGG enrichment indicated that the coumarin derivatives could induce significant changes of succinate dehydrogenase (SDH), Acetyl-coenzyme A synthetase (ACCA) and pyruvate dehydrogenase (PDH) genes, which contributed to the disorders of glucolipid metabolism and the dysfunction of mitochondrial. The results demonstrated that aminocoumarins with schiff-base as core moieties could be the promising lead compounds for the discovery of novel fungicides.


Asunto(s)
Cumarinas , Diseño de Fármacos , Cumarinas/farmacología , Cumarinas/química , Cumarinas/síntesis química , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Estructura Molecular , Fungicidas Industriales/farmacología , Fungicidas Industriales/síntesis química , Fungicidas Industriales/química , Relación Estructura-Actividad Cuantitativa , Botrytis/efectos de los fármacos
4.
Int J Mol Sci ; 24(13)2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37446158

RESUMEN

Pellicle biofilm-forming bacteria Bacillus amyloliquefaciens are the major spoilage microorganisms of soy products. Due to their inherent resistance to antibiotics and disinfectants, pellicle biofilms formed are difficult to eliminate and represent a threat to food safety. Here, we assessed linalool's ability to prevent the pellicle of two spoilage B. amyloliquefaciens strains. The minimum biofilm inhibitory concentration (MBIC) of linalool against B. amyloliquefaciens DY1a and DY1b was 4 µL/mL and 8 µL/mL, respectively. The MBIC of linalool had a considerable eradication rate of 77.15% and 83.21% on the biofilm of the two strains, respectively. Scanning electron microscopy observations revealed that less wrinkly and thinner pellicle biofilms formed on a medium supplemented with 1/2 MBIC and 1/4 MBIC linalool. Also, linalool inhibited cell motility and the production of extracellular polysaccharides and proteins of the biofilm matrix. Furthermore, linalool exposure reduced the cell surface hydrophobicity, zeta potential, and cell auto-aggregation of B. amyloliquefaciens. Molecular docking analysis demonstrated that linalool interacted strongly with quorum-sensing ComP receptor and biofilm matrix assembly TasA through intermolecular hydrogen bonds, hydrophobic contacts, and van der Waals forces interacting with site residues. Overall, our findings suggest that linalool may be employed as a potential antibiofilm agent to control food spoilage B. amyloliquefaciens.


Asunto(s)
Bacillus amyloliquefaciens , Simulación del Acoplamiento Molecular , Biopelículas
5.
Molecules ; 27(9)2022 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-35566096

RESUMEN

A series of 30 succinate dehydrogenase inhibitors (SDHIs) of 4-amino coumarin-based derivatives were designed and synthesized. According to the analysis of fungicidal activity in vitro, most of the compounds expressed broad-spectrum antifungal activity against four plant pathogenic fungi (Alternaria alternata, Alternaria solani, Fusarium oxysporum, and Botrytis cinerea) using the mycelium growth inhibition method. The results showed that compounds 3n with the group of 2-ene-3-methyl-butyl and 4e with the group of 2-bromo-1-oxo-hexyl displayed excellent activity against Alternaria alternata and Alternaria solani, with EC50 values of 92~145 µg/mL. Molecular docking showed that the inhibitor 3n was completely locked into the cavity of SDH, forming a conventional hydrogen bond interacting with the amino acid residue TYR58. The present work indicates that these derivatives would serve as novel potential fungicides targeting SDH.


Asunto(s)
Antifúngicos , Fungicidas Industriales , Alternaria , Aminocumarinas , Antifúngicos/química , Antifúngicos/farmacología , Botrytis , Cumarinas/farmacología , Fungicidas Industriales/farmacología , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad
6.
Molecules ; 27(23)2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36500229

RESUMEN

Xanthanolides were particularly characteristic of the genus Xanthium, which exhibited broad biological effects and have drawn much attention in pharmacological application. The review surveyed the structures and bioactivities of the xanthanolides in the genus Xanthium, and summarized the synthesis tactics of xanthanolides. The results indicated that over 30 naturally occurring xanthanolides have been isolated from the genus Xanthium in monomeric, dimeric and trimeric forms. The bioassay-guided fractionation studies suggested that the effective fractions on antitumor activities were mostly from weak polar solvents, and xanthatin (1) was the most effective and well-studied xanthanolide. The varieties of structures and structure-activity relationships of the xanthanolides had provided the promising skeleton for the further study. The review aimed at providing guidance for the efficient preparation and the potential prospects of the xanthanolides in the medicinal industry.


Asunto(s)
Xanthium , Xanthium/química , Fraccionamiento Químico
7.
Molecules ; 27(9)2022 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-35566352

RESUMEN

The aim of this study was to investigate the effects of microwave ultrasonic-assisted extraction (MUAE) on the content, structure, and biological functions of Brassica rapa L. polysaccharide (BRP). Response surface methodology (RSM) was used to optimize the parameters of MUAE, and it obtained a polysaccharide with yield of 21.802%. Then, a neutral polysaccharide named BRP-1-1 with a molecular weight of 31.378 kDa was isolated and purified from BRP using DEAE-650 M and Sephadex G-100. The structures of the BRP-1-1 were elucidated through a combination of FT-IR, GC-MS, NMR, and methylation analysis. The results showed that BRP-1 consisted of mannose (Man) and glucose (Glu) in a molar ratio of 7.62:1. The backbone of BRP-1-1 mainly consisted of →6)-α-D-Glup-(1→4-ß-D-Glup-(1→2)-α-D-Manp-(1→2)-α-D-Glup-(1→, the branch was [T-α-D-Manp-(1]n→. BRP-1-1 intervention significantly inhibited α-glucosidase activity; an inhibition rate of 44.623% was achieved at a concentration of 0.5 mg/mL. The results of the in vitro biological activity showed that BRP-1-1 has good antioxidant and hypoglycemic activity, suggesting that BRP-1-1 could be developed as a functional medicine.


Asunto(s)
Antioxidantes , Brassica rapa , Antioxidantes/química , Humanos , Hipoglucemiantes/farmacología , Peso Molecular , Polisacáridos/química , Espectroscopía Infrarroja por Transformada de Fourier
8.
Molecules ; 27(1)2022 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-35011513

RESUMEN

Intelligent stimulus-triggered release and high drug-loading capacity are crucial requirements for drug delivery systems in cancer treatment. Based on the excessive intracellular GSH expression and pH conditions in tumor cells, a novel glutathione (GSH) and pH dual-responsive hydrogel was designed and synthesized by conjugates of glutamic acid-cysteine dendrimer with alginate (Glu-Cys-SA) through click reaction, and then cross-linked with polyethylene glycol (PEG) through hydrogen bonds to form a 3D-net structure. The hydrogel, self-assembled by the inner disulfide bonds of the dendrimer, is designed to respond to the GSH heterogeneity in tumors, with a remarkably high drug loading capacity. The Dox-loaded Glu-Cys-SA hydrogel showed controlled drug release behavior, significantly with a release rate of over 76% in response to GSH. The cytotoxicity investigation indicated that the prepared DOX-loaded hydrogel exhibited comparable anti-tumor activity against HepG-2 cells with positive control. These biocompatible hydrogels are expected to be well-designed GSH and pH dual-sensitive conjugates or polymers for efficient anticancer drug delivery.


Asunto(s)
Alginatos , Antineoplásicos , Dendrímeros , Doxiciclina , Hidrogeles , Neoplasias/tratamiento farmacológico , Alginatos/química , Alginatos/farmacocinética , Alginatos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Dendrímeros/química , Dendrímeros/farmacocinética , Dendrímeros/farmacología , Doxiciclina/química , Doxiciclina/farmacocinética , Doxiciclina/farmacología , Células Hep G2 , Humanos , Hidrogeles/síntesis química , Hidrogeles/química , Hidrogeles/farmacocinética , Hidrogeles/farmacología , Ratones , Neoplasias/metabolismo
9.
Molecules ; 23(11)2018 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-30453559

RESUMEN

Umbelliferone was discovered to be an important allelochemical in our previous study, but the contribution of its activity and structure has not yet been revealed. In this study, a series of analogues were synthesized to determine the skeleton of umbelliferone and examine its fungicidal activity. Furthermore, targeted modifications were conducted with three plant parasitic fungi to examine the lead compounds. Among those tested, compounds 2f and 10 were found to show excellent antifungal activity with an inhibitory rate over 80% at 100 ug/mL. The study proves that umbelliferone can be a promising skeleton for fungicides discovery. In addition, the primary structure⁻activity relationship provides a good guidance for the discovery of novel fungicides based on natural products in the future.


Asunto(s)
Antifúngicos/síntesis química , Antifúngicos/farmacología , Hongos/efectos de los fármacos , Feromonas/química , Umbeliferonas/química , Umbeliferonas/farmacología , Diseño de Fármacos , Fungicidas Industriales , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Plantas/parasitología
10.
J Food Sci Technol ; 55(1): 366-375, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29358829

RESUMEN

Biofortification of crops with exogenous iodine is a novel strategy to control iodine deficiency disorders (IDD). The bioaccessibility of iodine (BI) in the biofortified vegetables in the course of soaking, cooking and digestion, were examined. Under hydroponics, the concentration of iodine in leafstalks of the celery and pakchoi increased with increasing exogenous iodine concentration, 54.8-63.9% of the iodine absorbed by pakchoi was stored in the soluble cellular substance. Being soaked in water within 8 h, the iodine loss rate of the biofortified celery was 3.5-10.4% only. More than 80% of the iodine in the biofortified celery was retained after cooking under high temperature. The highest BI of the biofortified vegetables after digestion in simulated gastric and intestinal juice amounted to 74.08 and 68.28%, respectively. Factors influencing BI included pH, digestion duration, and liquid-to-solid ratio. The high BI of the biofortified vegetables provided a sound reference for the promotion of iodine biofortification as a tool to eliminate the IDD.

11.
Microb Pathog ; 104: 110-115, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28089948

RESUMEN

Umbelliferone was an important allelochemical with a wide spectrum bioactivity. In our previous study, C7 hydroxy in the backbone of umbelliferone was identified to be responsible for its phytotoxicity and the targeted modification of the above site could lead to the phytotoxicity loss. In view of this, a series of hydroxycoumarins and C7 O-substituted umbelliferone derivatives were efficiently synthesized to evaluate their antifungal activity against four phytopathogenic fungi. Most of them, as we predicted, exhibited improved fungicidal activity. The phytotoxicity of effective compounds was also assayed by Lactuca sativa to investigate their side effects on plant growth. Compounds 9 and 17 were identified to show strong antifungal activity with low phytotoxicity. A brief investigation on structure-activity relationships revealed that the modification at the C7 hydroxy of umbelliferone could be a promising way to enhance the antifungal activity with decreasing the phytotoxicity.


Asunto(s)
Antifúngicos/síntesis química , Antifúngicos/farmacología , Umbeliferonas/síntesis química , Umbeliferonas/farmacología , Descubrimiento de Drogas , Hongos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad
12.
Microb Pathog ; 95: 186-192, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27079471

RESUMEN

As organosulfur and organophosphorus agents, phaltane and phosmet are facing great challenges for the environmental contamination, mammalian toxicity and increasing resistance with long term use. It is efficient and meaningful to develop phthalimide-based alternatives with non-sulfur and non-phosphorus groups. A series of N-substituted phthalimides were synthesized and their antifungal activity against two disastrous phytopathogenic fungi, Alternaria solani and Botrytis cinerea was evaluated in vitro. Most of them showed significant antifungal activity against both of fungi, or either of them selectively. N-vinylphthalimide (4) and 8-[4-(phthalimide-2-yl) butyloxy] quinoline (13) were identified as the most promising candidates against B. cinerea and A. solani with the IC50 values of 7.92 µg/mL and 10.85 µg/mL respectively. The brief structure-activity relationships have revealed that vinyl, quinolyl, bromide alkyl and benzyl substitutions were appropriate substituents and coupling functional moieties indirectly with optimum alkyl chain was efficient to prepare phthalimides related fungicides.


Asunto(s)
Alternaria/efectos de los fármacos , Antifúngicos/síntesis química , Antifúngicos/farmacología , Botrytis/efectos de los fármacos , Ftalimidas/síntesis química , Ftalimidas/farmacología , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular
13.
Ann Vasc Surg ; 32: 41-9, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26802295

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the clinical significance of the involvement of collateral vessels in interventional therapy based on the angiosome concept for infrapopliteal critical limb ischemia (CLI). METHODS: We enrolled 486 patients with unilateral infrapopliteal CLI (Rutherford Stage 5 or 6) treated at 2 hospitals from January 2005 to December 2014. Using the angiosome concept, the patients were categorized into 3 groups: the direct revascularization (DR) group, the indirect revascularization through collaterals (IR-tc) group, and the indirect revascularization without collaterals (IR-wc) group. The data from 1 year of follow-up after the initial surgery were analyzed for all 3 groups. RESULTS: During the 1-year follow-up, the unhealed ulcer rate of the IR-wc group was significantly higher than that of the DR group (83.4% vs. 31.7%, P < 0.001) and the IR-tc group (83.4% vs. 34.8%, P < 0.001). Furthermore, the limb salvage rate of the IR-wc group was significantly lower than that of the DR group (70.4% vs. 89.2%, P < 0.001) and the IR-tc group (70.4% vs. 85.4%, P = 0.0013). However, there were no differences in the unhealed ulcer rate or the limb salvage rate between the DR group and the IR-tc group (31.7% vs. 34.8%, P = 0.096 and 89.2% vs. 85.4%, P = 0.2834, respectively). In addition, within the IR-wc group, the unhealed ulcer rate of diabetic patients was higher than that of patients without diabetes (90.0% vs. 74.6%, P = 0.0116), but there was no difference in the limb salvage rate between diabetic and nondiabetic patients. No differences in the unhealed ulcer rate or the limb salvage rate were found between diabetic and nondiabetic patients in the other 2 groups. CONCLUSIONS: Following the angiosome model of perfusion for endovascular therapy, directly revascularizing the feeding artery and indirectly achieving revascularization through collaterals can effectively prompt the healing of ulcers and decrease the amputation rate in patients with infrapopliteal CLI. Collateral vessels play a crucial role in the treatment of ischemic foot.


Asunto(s)
Circulación Colateral , Procedimientos Endovasculares , Isquemia/cirugía , Extremidad Inferior/irrigación sanguínea , Modelos Cardiovasculares , Enfermedad Arterial Periférica/cirugía , Arteria Poplítea/cirugía , Anciano , Amputación Quirúrgica , China , Enfermedad Crítica , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Isquemia/diagnóstico por imagen , Isquemia/fisiopatología , Estimación de Kaplan-Meier , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/fisiopatología , Flujo Sanguíneo Regional , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Cicatrización de Heridas
14.
J Basic Microbiol ; 55(10): 1239-44, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26058971

RESUMEN

A strain SMrs28 was isolated from the rhizosphere soil of a toxic plant Stellera chamaejasme and identified as Bacillus sp. on the basis of morphological and partial 16S rRNA gene sequence analysis. The crude extract of SMrs28 fermentation broth showed strong nematocidal activities in preliminary test. To define the active nematocidal metabolites of SMrs28, a novel compound (1), 4-oxabicyclo[3.2.2]nona-1(7), 5,8-triene, along with five known compounds (2-6), were isolated from the strain by various column chromatographic techniques and characterized on the basis of spectroscopic analysis. Results of the in vitro nematicidal tests showed that the metabolites presented different levels of activity at certain exposure conditions. Compounds (1-3) displayed LC50 values of 904.12, 451.26, 232.98 µg/ml and 1594.0, 366.62, 206.38 µg/ml against Bursaphelenchus xylophilus and Ditylenchus destructor at 72 h, respectively. This is the first report of the nematicidal activity of the compounds as constituents of Bacillus sp.. Our findings help to find potential chemical structures to develop nematicides from microbial source for the management of nematode-infected plant diseases.


Asunto(s)
Antinematodos/aislamiento & purificación , Antinematodos/farmacología , Bacillus/química , Bacillus/metabolismo , Animales , Fermentación , Estructura Molecular , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/prevención & control , ARN Ribosómico 16S , Rizosfera , Análisis de Secuencia de ARN , Microbiología del Suelo , Tylenchida/efectos de los fármacos , Tylenchoidea/efectos de los fármacos
15.
Parasitol Res ; 112(11): 3825-33, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23949244

RESUMEN

Coccidiosis is one of the most important protozoan diseases and inflicts severe economic losses on the poultry industry. The aim of this study was to evaluate the capacity of Bacillus Calmette-Guerin (BCG) to deliver apical membrane antigen1 (AMA1) of Eimeria maxima to stimulate specific cellular and humoral immune responses in chickens. Day-old birds were immunized twice with rBCG/pMV261-AMA1, rBCG/pMV361-AMA1, or BCG via oral, intranasal, and subcutaneous routes and then orally challenged with homologous E. maxima sporulated oocysts. Gain of body weight, fecal oocyst output, lesion scores, serum antibody responses, numbers of splenocyte CD4(+) and CD8(+) T cells, and gut cytokine transcript levels were assessed as measures of protective immunity. Challenge experiments demonstrated that rBCG vaccination via intranasal or subcutaneous routes could increase weight gain, decrease intestinal lesions, and reduce fecal oocyst shedding, and the subcutaneous and intranasal routes were superior to the oral route based on the immune effects. Furthermore, intranasal rBCG immunization could also lead to a significant increase in serum antibody, the percentage of CD4+ and CD8+ T lymphocyte cells, and the levels of IL-1ß, IFN-γ, IL-15, and IL-10 mRNAs compared with the control group. These results suggested that intranasal rBCG immunization could induce a strong humoral and cellular response directed against homologous E. maxima infection. This study provides data for the use of rBCG to develop a prophylactic vaccine against coccidiosis.


Asunto(s)
Antígenos de Protozoos/inmunología , Coccidiosis/veterinaria , Portadores de Fármacos , Eimeria/inmunología , Mycobacterium bovis/genética , Enfermedades de las Aves de Corral/prevención & control , Vacunas Antiprotozoos/inmunología , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/genética , Peso Corporal , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Pollos , Coccidiosis/inmunología , Coccidiosis/patología , Coccidiosis/prevención & control , Citocinas/biosíntesis , Eimeria/genética , Heces/parasitología , Perfilación de la Expresión Génica , Vectores Genéticos , Carga de Parásitos , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/patología , Vacunas Antiprotozoos/administración & dosificación , Vacunas Antiprotozoos/genética , Índice de Severidad de la Enfermedad , Vacunación/métodos
16.
Chem Pharm Bull (Tokyo) ; 61(2): 204-11, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23221611

RESUMEN

By employing sanguinarine, a natural active quaternary isoquinoline alkaloid, as a model molecule, a series of structurally simple quaternary 2-aryl-3,4-dihydroisoquinolin-2-ium compounds were designed and synthesized and evaluated for in vitro acaricidal activity against P. cuniculi. A new approach towards the title compounds was developed with isochroman as starting material. The results showed that 22 of 24 tested compounds displayed the activity in varying degrees at 0.4 mg/mL. Fourteen compounds were significantly more effective than ivermectin, a standard acaricide, and 6-methoxy dihydrosanguinarine, a derivative of sanguinarine (p<0.05). And their comprehensive relative activity was 1.4 to 16.5 times than that of ivermectin and 1.5 to 18.8 times than that of 6-methoxy dihydrosanguinarine. The structure-activity relationship indicated that the introduction of a substituent to N-benzene ring, especially halogen atom and trifluoromethyl group, led to great improvement of the activity. The position of fluorine atom, methyl group and hydroxyl group made very significant effects on the activity. It was concluded that 2-aryl-3,4-dihydroisoquinolin-2-iums are very promising candidates for the development of new isoquinoline acaricidal agents.


Asunto(s)
Acaricidas/síntesis química , Benzofenantridinas/química , Isoquinolinas/química , Psoroptidae/efectos de los fármacos , Acaricidas/química , Acaricidas/toxicidad , Animales , Bromuros/química , Flúor/química , Isoquinolinas/síntesis química , Isoquinolinas/toxicidad , Relación Estructura-Actividad
17.
Heliyon ; 9(2): e13134, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36747552

RESUMEN

Given the problems of unclear division of evaluation factors, inadequate utilization of objective data and unreasonable distribution of weight in college performance measurement, this study extracts relevant indicators and quantitative data from the survey report of administrational institutions, and constructs a comprehensive performance measurement model based on the integration of fuzzy Delphi method (FDM), Entropy weight method (EWM), and grey relational analysis (GRA). The study seeks to identify differences in measurement analysis by comparing the weights, the performance and the rankings of the alternatives about higher vocational colleges in Zhejiang province. Finally, the results show the following: (1) by FDM, 33 indicators about colleges' performance are selected to form the evaluation system of the college's performance, (2) the indicators' weights are obtained through EWM and GRA, and a nonparametric test shows that there is no significant difference between the two types of weights, (3) the grey relational degrees of the alternatives are obtained and ranked on the basis of comprehensive evaluation model. By nonparametric test, there is a significant difference between the two types of relational degrees. On the contrary, no significant difference is found in the ranking of relational degrees, (4) based on the analysis results, this study further compares the performance of alternatives in different forms. There are significant differences between the performance of public colleges and private colleges, while no significant differences are observed between the performance of vocational colleges in Hangzhou and non-Hangzhou. Given the reliability and validity of the model, the comprehensive measurement model provides a relatively objective reference for college governance and administrational institutions, and also becomes an effective tool of colleges' evaluation to assist and improve the management practice in educational institutions.

18.
J Immunol Res ; 2023: 5990156, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37032653

RESUMEN

As a protective mechanism regulating excessive inflammation, endotoxin tolerance plays a vital role in regulating endotoxin shock. Kupffer cells are players in mediating endotoxin tolerance. Nonetheless, the regulatory mechanism regulating endotoxin tolerance is barely known. A nonclassical IKK kinase called TRAF-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) can regulate inflammation. Here, we found that TBK1 is required for endotoxin tolerance in Kupffer cells. TBK1 plays a dominant role in regulating endotoxin tolerance by negatively regulating the induction of p100 processing. Deltex E3 ubiquitin ligase 4 (DTX4), a negative regulator of TBK1, can promote TBK1 K48-mediated ubiquitination and indirectly regulate endotoxin tolerance in Kupffer cells. We demonstrate that the c-Myb transcription factor could negatively regulate DTX4. Overexpression of c-Myb can be used to reduce the ubiquitination of TBK1 by reducing DTX4 transcription and to boost the anti-inflammatory effect of endotoxin tolerance. Thus, this study reveals a novel theory of TBK1-mediated endotoxin tolerance in Kupffer cells.


Asunto(s)
Proteínas Serina-Treonina Quinasas , Transducción de Señal , Humanos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Macrófagos del Hígado/metabolismo , Tolerancia a Endotoxinas , Inflamación
19.
J Chromatogr A ; 1690: 463786, 2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36641939

RESUMEN

In this work, a solute retention optimization method (SRO) was proposed to exploit the purification potential of two-dimensional liquid chromatography (2D-LC). According to our findings, the complementarity of 2D-LC correlates with some specific impurities. In the two methods used in 2D-LC, the retention order of these impurities and target compound is completely opposite. Taking full advantage of the complementarity is crucial to enhance the saturation capacity (wmax) of 2D-LC by SRO. For the purpose of validating the effectiveness of SRO, a reverse-phase liquid chromatography (RPLC) coupled with hydrophilic interaction chromatography (HILIC) was developed to purify p-chlorobenzoic acid from substituted benzenes. By using the overloading effects of analytes as indicators, the wmax of RPLC × HILIC was determined by the bisection method, and finally defined by the extremely high loading volume of 4.9 mL. A touch-peak separation of impurities and the target compound occurred precisely during the secondary separation. The effectiveness of SRO was also verified by the greater purification efficiency of RPLC × HILIC than that of HILIC × RPLC. Subsequently, a RPLC × RPLC method was developed by SRO to prepare the reference materials of caffeine from tea extracts. Only by an analytical C18 column, 15.6 mg of caffeine with the purity of 98.3% was obtained at once with the recovery up to 82.3%. However, without the aid of SRO, the purity rapidly decreased to 62.0%. Compared to other methods, SRO-based 2D-LC offers certain advantages in terms of purity, recovery, and the purification efficiency, suggesting that it is particularly effective in developing preparative 2D-LC facing complex matrices.


Asunto(s)
Cafeína , Cromatografía de Fase Inversa , Cromatografía de Fase Inversa/métodos , Interacciones Hidrofóbicas e Hidrofílicas
20.
Food Res Int ; 163: 112278, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36596188

RESUMEN

The flavor and aroma quality of green tea are closely related to the harvest season. The aim of this study was to identify the harvesting season of green tea by alcohol/salt-based aqueous two-phase system (ATPS) combined with chemometric analysis. In this paper, the single factor experiments (SFM) and response surface methodology (RSM) optimization were designed to investigate and select the optimal ATPS. A total of 180 green tea samples were studied in this work, including 86 spring tea and 94 autumn tea. After the active components in green tea samples were extracted by the optimal ethanol/(NH4)2SO4 ATPS, the qualitative and quantitative analysis was realized based on HPLC-DAD combined with alternating trilinear decomposition-assisted multivariate curve resolution (ATLD-MCR) algorithm, with satisfactory spiked recoveries (86.00 %-112.45 %). The quantitative results obtained from ATLD-MCR model were subjected to chemometric pattern recognition analysis. The constructed partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) models showed better results than the principal component analysis (PCA) model, and the R2Xcum values (>0.835) and R2Ycum (>0.937) were close to 1, the Q2cum values were greater than 0.75 (>0.933), and the differences between R2Ycum and Q2cum were not larger than 0.2, indicating excellent cross-validation prediction performance of the models. Furthermore, the classification results based on the hierarchical clustering analysis (HCA) were consistent with the PCA, PLS-DA and OPLS-DA results, establishing a good correlation between tea active components and the harvesting seasons of green tea. Overall, the combination of ATPS and chemometric methods is accurate, sensitive, fast and reliable for the qualitative and quantitative determination of tea active components, providing guidance for the quality control of green tea.


Asunto(s)
Quimiometría , , Estaciones del Año , Análisis Discriminante , Etanol , Cloruro de Sodio , Cloruro de Sodio Dietético
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