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1.
J Asian Nat Prod Res ; 25(9): 880-889, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36573490

RESUMEN

Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.


Asunto(s)
Diabetes Mellitus Tipo 2 , Proteínas Proto-Oncogénicas c-akt , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glicósidos/farmacología , Antioxidantes
2.
Sensors (Basel) ; 22(8)2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35458938

RESUMEN

Educational robotics is an effective carrier of information technology education, making its way into classrooms. However, the design of the educational robotic arm kit and the study on the effect of robotic arms on students' thinking literacy remain to be completed. In this paper, iArm, a 6-DOF robotic arm consisting of a drive chassis, an arm body, and end tools, is presented. Its auxiliary modules, including the vision module and conveyor belt, and the curriculum targeting students' computational thinking are also developed to refine the current educational robotic arm kit. Furthermore, to explore the effectiveness of the iArm kit, thirteen high school students participated in the semester-long curriculum, completed assigned projects, and filled out the pre-test and post-test scales. By formative and summative evaluation, the result shows that the iArm kit effectively enhanced students' computational thinking.


Asunto(s)
Curriculum , Estudiantes , Competencia Clínica , Evaluación Educacional , Humanos
3.
BMC Gastroenterol ; 20(1): 339, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-33059584

RESUMEN

BACKGROUND: Multiple murine models of nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) have been established by using obesogenic diets and/or chemical induction. MS-NASH mouse (formally FATZO) is a spontaneously developed dysmetabolic strain that can progress from hepatosteatosis to moderate fibrosis when fed a western diet supplemented with 5% fructose (WDF). This study aimed to use carbon tetrachloride (CCl4) to accelerate and aggravate progression of NAFLD/NASH in MS-NASH mouse. METHODS: Male MS-NASH mice at 8 weeks of age were fed WDF for the entire study. Starting at 16 weeks of age, CCl4 was intraperitoneally administered twice weekly at a dose of 0.2 mL/kg for 3 weeks or 0.08 mL/kg for 8 weeks. Obeticholic acid (OCA, 30 mg/kg, QD) was administered in both MS-NASH and C57Bl/6 mice fed WDF and treated with CCl4 (0.08 mL/kg). RESULTS: WDF enhanced obesity and hepatosteatosis, as well as induced moderate fibrosis in MS-NASH mice similar to previous reports. Administration of CCl4 accelerated liver fibrosis with increased bridging and liver hydroxyproline contents, but had no significant impact on liver steatosis and lipid contents. High dose CCl4 caused high mortality and dramatic elevation of ALT and ASL, while low dose CCl4 resulted in a moderate elevation of ALT and AST with low mortality. Compared to C57BI/6 mice with WDF and CCl4 (0.08 mL/kg), MS-NASH mice had more prominent hepatosteatosis and fibrosis. OCA treatment significantly lowered liver triglycerides, steatosis and fibrosis in both MS-NASH and C57Bl/6 mice fed WDF with CCl4 treatment. CONCLUSIONS: CCl4 reduced induction time and exacerbated liver fibrosis in MS-NASH mice on WDF, proving a superior NASH model with more prominent liver pathology, which has been used favorably in pharmaceutical industry for testing novel NASH therapeutics.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Tetracloruro de Carbono , Dieta Alta en Grasa/efectos adversos , Dieta Occidental , Modelos Animales de Enfermedad , Fructosa , Hígado , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico
4.
J Autoimmun ; 100: 84-94, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30872080

RESUMEN

TREX1 encodes a major cellular DNA exonuclease. Mutations of this gene in human cause cellular accumulation of DNA that triggers autoimmune diseases including Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE). We created a lupus mouse model by engineering a D18 N mutation in the Trex1 gene which inactivates the enzyme and has been found in human patients with lupus-like disorders. The Trex1D18N/D18N mice exhibited systemic inflammation that consistently recapitulates many characteristics of human AGS and SLE. Importantly, ablation of cGas gene in the Trex1D18N/D18N mice rescued the lethality and all detectable pathological phenotypes, including multi-organ inflammation, interferon stimulated gene induction, autoantibody production and aberrant T-cell activation. These results indicate that cGAS is a key mediator in the autoimmune disease associated with defective TREX1 function, providing additional insights into disease pathogenesis and guidance to the development of therapeutics for human systemic autoimmune disorders.


Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso , Exodesoxirribonucleasas , Lupus Eritematoso Sistémico , Activación de Linfocitos , Mutación Missense , Malformaciones del Sistema Nervioso , Nucleotidiltransferasas , Fosfoproteínas , Linfocitos T/inmunología , Sustitución de Aminoácidos , Animales , Enfermedades Autoinmunes del Sistema Nervioso/genética , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/patología , Modelos Animales de Enfermedad , Activación Enzimática/genética , Activación Enzimática/inmunología , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/inmunología , Humanos , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Ratones , Ratones Mutantes , Malformaciones del Sistema Nervioso/genética , Malformaciones del Sistema Nervioso/inmunología , Malformaciones del Sistema Nervioso/patología , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/inmunología , Fosfoproteínas/genética , Fosfoproteínas/inmunología , Linfocitos T/patología
5.
Mikrochim Acta ; 186(5): 303, 2019 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-31028477

RESUMEN

A method is described for the fluorometric determination of DNA containing oxidatively damaged product 8-hydroxy-2'-deoxyguanosine (DNA-8-OHdG). Carbon dots (CDs) were modified with glutaraldehyde for DNA conjugation, and antibody against 8-OHdG was immobilized on gold nanoparticles (AuNPs). The presence of DNA-8-OHdG can be linked to CDs by reaction of amino groups on DNA with glutaraldehyde. AuNPs were brought closely to CDs by specific immune reaction between 8-OHdG and antibody on AuNPs. Under 350 nm photoexcitation, the emission of CDs with a peak at 440 nm is quenched by the AuNPs and not restored. In the presence of DNA-8-OHdG, the measured fluorescence intensity decreases and quenching efficiency increases. The limit of detection is 700 pM, and the assay works in the 0.01 nM to 25 µM DNA-8-OHdG concentration range. The method is perceived to possess a good potential as a tool for detecting biomarkers for DNA damage due to oxidative stress. Graphical abstract A fluorometric immunoassay for detecting 8-hydroxy-2'-deoxyguanosine (8-OHdG) in oxidatively damaged DNA is reported. It is based on the use of carbon dots (CDs) and gold nanoparticles (AuNPs). Black wavy lines represent DNA. Yellow polygonal sharps represent 8-OHdG. Blue and pink balls represent CDs and AuNPs, respectively.


Asunto(s)
8-Hidroxi-2'-Desoxicoguanosina/análisis , Carbono/química , Daño del ADN , Oro/química , Inmunoensayo/métodos , Nanopartículas del Metal/química , Estrés Oxidativo/genética , 8-Hidroxi-2'-Desoxicoguanosina/orina , Biomarcadores/análisis , Biomarcadores/orina , Fluorometría , Humanos , Concentración de Iones de Hidrógeno , Límite de Detección
6.
Molecules ; 24(17)2019 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-31443342

RESUMEN

Histamine can be formed by enzymatic decarbonylation of histidine, which is an important indicator of seafood quality. A rapid and sensitive assay method is necessary for histamine monitoring. A fluorescence resonance energy transfer (FRET) assay system based on a carbon dot (CD)-modified nanoporous alumina membrane and Fe3O4@Au magnet nanocomposites has been developed for histamine detection in mackerel fish. CDs immobilized on nanoporous alumina membranes were used as donors, which provided a fluorescence sensing substrate for histamine detection. Fe3O4@Au magnet nanocomposites can not only act as acceptors, but also concentrate histamine from fish samples to increase detection sensitivity. Histamine was detected by the fluorescence signal changes of CDs capturing histamine by an immune reaction. The fluorescence signals of CDs were quenched by Fe3O4@Au magnet nanocomposites via the FRET mechanism. With an increase of histamine, the fluorescence intensity decreased. By recording fluorescence spectra and calculating intensity change, histamine concentration can be determined with a limit of detection (LOD) of 70 pM. This assay system can be successfully applied for histamine determination in mackerel fish to monitor the fish spoilage process in different storage conditions. It shows the potential applications of CDs-modified nanoporous alumina membranes and Fe3O4@Au magnet nanocomposites-based biosensors in the food safety area.


Asunto(s)
Carbono , Compuestos Férricos/química , Transferencia Resonante de Energía de Fluorescencia , Histamina/análisis , Membranas Artificiales , Nanocompuestos , Nanoporos , Puntos Cuánticos , Óxido de Aluminio/química , Técnicas Biosensibles/métodos , Técnicas Biosensibles/normas , Carbono/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Transferencia Resonante de Energía de Fluorescencia/normas , Límite de Detección , Nanocompuestos/química , Nanocompuestos/ultraestructura , Difracción de Rayos X
7.
Cell Biol Int ; 42(10): 1370-1376, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29957876

RESUMEN

Liver fibrosis is a major cause of morbidity and mortality worldwide, and the outcome of various chronic liver diseases. Recent studies suggest that aberrant expression of miR-34 is involved in the progression of various liver diseases including hepatocellular carcinoma (HCC). However, it is still poorly understood whether miR-34 mediates the pathogenesis of liver fibrosis. Here, we found that the expression of microRNA-34a-5p (miR-34a-5p) was significantly decreased in patients with hepatitis B virus (HBV)-activated liver fibrosis and HCC, as well as in CC14 (Carbon tetrachloride Tetrachloromethane) induced liver fibrosis model mice. The TGF-ß1/Smad3 (Transforming growth factor-ß1/Smad3) pathway were significantly augmented in CC14 induced mice compared with normal control, whereas inhibitor of TGF-ß1 (SB431542) significantly attenuated liver fibrosis and TGF-ß1/Smad3 activation. Administration of the miR-34a-5p mimic de-activated TGF-ß1/Smad3 pathway in human hepatic stellate cells (HSC), LX-2. Moreover, the target gene for miR-34a-5p, Smad4, was predicted and verified in LX-2 cells. Taken together, these data demonstrated that overexpression of miR-34 in HSCs ameliorated the development and progression of liver fibrosis by targeting Smad4 and regulating TGF-ß1/Smad3 pathway. Strategies targeting miR-34a-5p may be of benefit in the treatment of liver fibrosis.


Asunto(s)
Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/genética , MicroARNs/biosíntesis , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Células Estrelladas Hepáticas/citología , Células Estrelladas Hepáticas/patología , Hepatitis B/genética , Hepatitis B/metabolismo , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/terapia , Cirrosis Hepática/virología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ratones , Ratones Endogámicos C57BL , MicroARNs/administración & dosificación , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Transducción de Señal , Transfección
8.
Langmuir ; 32(12): 3079-84, 2016 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-26986041

RESUMEN

Highly cross-linked poly(divinylbenzene) (PDVB) spherical colloidal particles with nano-, submicron-, and micron-sizes of 157.2 nm, 602.1 nm, and 5.1 µm were synthesized through emulsion and dispersion polymerization methods. The influences of particle size on the surface morphology, roughness, superhydrophobicity, and critical cracking thickness of colloidal films were studied in detail. The results show that PDVB colloidal films possess large water contact angle (CA) over 151°, belonging to superhydrophobic materials. Moreover, it is interesting to observe that the highly cross-linked network structure leads to PDVB film's excellent heat-resistance. The CA and rough surface morphology remain nearly unchanged after thermal-treatment of films at 150 °C for 24 h. In addition, no cracks were observed in films with thicknesses up to 8.1 µm, exceeding most of polymer and inorganic particle films reported in the literature. The simple and scalable preparation method, low-cost, superhydrophobicity, and excellent thermal stability endow the PDVB colloidal films with promising applications in advanced coating fields, especially when employed in the high-temperature service environment.

9.
Sensors (Basel) ; 16(10)2016 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-27782087

RESUMEN

Histamine is an indicator of food quality and indispensable in the efficient functioning of various physiological systems. Rapid and sensitive determination of histamine is urgently needed in food analysis and clinical diagnostics. Traditional histamine detection methods require qualified personnel, need complex operation processes, and are time-consuming. In this study, a biofunctionalized nanoporous alumina membrane based electrochemical biosensor with magnetic nanoparticles (MNPs) concentration and signal amplification was developed for histamine determination. Nanoporous alumina membranes were modified by anti-histamine antibody and integrated into polydimethylsiloxane (PDMS) chambers. The specific antibody modified MNPs were used to concentrate histamine from samples and transferred to the antibody modified nanoporous membrane. The MNPs conjugated to histamine were captured in the nanopores via specific reaction between histamine and anti-histamine antibody, resulting in a blocking effect that was amplified by MNPs in the nanopores. The blockage signals could be measured by electrochemical impedance spectroscopy across the nanoporous alumina membrane. The sensing platform had great sensitivity and the limit of detection (LOD) reached as low as 3 nM. This biosensor could be successfully applied for histamine determination in saury that was stored in frozen conditions for different hours, presenting a potentially novel, sensitive, and specific sensing system for food quality assessment and safety support.

11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(3): 303-10, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25832539

RESUMEN

OBJECTIVE: To investigate the effect of social support and coping style on the stress and mental health in relatives of patients with traumatic brain injury. METHODS: The stress, mental health, social support and coping style were investigated in 300 relatives of patients with traumatic brain injury by Relative Stress Scale, Symptom Checklist-90, Social Support Rating Scale and Simplified Coping Style Questionnaire in Changsha City. RESULTS: The mental health problems in relatives of patients with traumatic brain injury were closely related to the levels of stress, the ways of coping and the social support. In addition to the direct eff ect of stress on mental health in relatives of patients, the ways of coping and social support functioned as a mediator in this regard. The value of mesomeric eff ect for coping styles and social support ranged from 23.6% to 43.0%, and social support had an advantage over the coping styles. CONCLUSION: Social support and coping styles should be considered in psychological nursing program to prevent and adjust the mental distress in relatives of patients with traumatic brain injury, which is beneficial to the treatment and recovery for patients.


Asunto(s)
Adaptación Psicológica , Lesiones Encefálicas , Familia/psicología , Salud Mental , Apoyo Social , Humanos , Estrés Psicológico , Encuestas y Cuestionarios
12.
Bioorg Med Chem Lett ; 24(6): 1496-501, 2014 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-24582981

RESUMEN

A variety of new mono-oxazolidinone molecules by modifying the C-ring of Linezolid, a marketed antibiotic for MRSA, were synthesized and tested for their in vitro antibacterial activities against several Staphylococcus aureus, Mycobacterium smegmatis and two Gram-negative bacteria strains (Escherichia coli and Pseudomonas aeruginosa). Among them, compounds 4-7 displayed moderate antimicrobial activities. After development of a second oxazolidinone ring in the western part of the mono-oxazolidinone compounds 4-7 by a ring closure reaction with N,N'-carbonyldiimidazole (CDI), we found thus obtained bis-oxazolidinone compounds 22-25 possess excellently inhibitory activities against H37Rv but poor or no effects on other test bacteria. Among them, bis-oxazolidinone compound 22 and 24 are the most potent two compounds with a same MIC value of 0.125µg/mL against H37Rv virulent strain. Compound 22 also exhibited extremely low cytotoxicity on monkey kidney Vero cells with a selective index (IC50/MIC) over 40,000, which suggested bis-oxazolidinone compound 22 is a promising lead compound for subsequent investigation in search of new antitubercular agents.


Asunto(s)
Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Oxazolidinonas/química , Animales , Antituberculosos/síntesis química , Antituberculosos/química , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Evaluación Preclínica de Medicamentos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Mycobacterium smegmatis/efectos de los fármacos , Oxazolidinonas/síntesis química , Oxazolidinonas/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Células Vero
13.
Biochem Biophys Res Commun ; 436(2): 259-64, 2013 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-23726914

RESUMEN

Aspirin and valproic acid (VPA) have been extensively studied for inducing various malignancies growth inhibition respectively, despite their severe side effects. Here, we developed a novel combination by aspirin and VPA on hepatocellular cancer cells (HCCs). The viability of HCC lines were analyzed by MTT assay, apoptotic analysis of HepG2 and SMMC-7721 cell was performed. Real time-PCR and Western blotting were performed to determine the expression of apoptosis related genes and proteins such as Survivin, Bcl-2/Bax, Cyclin D1 and p15. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish murine model, and then therapeutic effect was analyzed after drug combination therapy. The viability of HCC lines' significantly decreased after drug combination treatment, and cancer cell apoptosis in combination group increasingly induced compared with single drug use. Therapeutic effect was significantly enhanced by combination therapy in tumor volume and tumor weight decrease. From the data shown here, aspirin and VPA combination have a synergistic killing effect on hepatocellular cancers cells proliferation and apoptosis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Aspirina/administración & dosificación , Aspirina/farmacología , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Sinergismo Farmacológico , Expresión Génica/efectos de los fármacos , Células Hep G2 , Inhibidores de Histona Desacetilasas/administración & dosificación , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Carga Tumoral/efectos de los fármacos , Carga Tumoral/genética , Ácido Valproico/administración & dosificación , Ácido Valproico/farmacología
14.
J Surg Res ; 182(2): e69-77, 2013 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-23207171

RESUMEN

BACKGROUND: Neurite outgrowth inhibitor-A (Nogo-A), myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein are three myelin-associated proteins that act as inhibitors to central nervous system regeneration. Neurite outgrowth inhibitor-A imposes the strongest effect on inhibiting axonal regeneration after traumatic brain injury. Alpha-tocopherol, a member of the vitamin E family, is recognized as an active antioxidative substance. Its use has not been well studied in brain injury research, especially in axonal regeneration research. METHODS: We obtained 99 intact adult male Sprague-Dawley rats (200-250 g) from the Experimental Animal Center of Central South University. We used the modified method of Freeney to generate moderate brain injury in the rats. We injected 600 mg/kg α-tocopherol intraperitoneally daily as traumatic brain injury (TBI) treatment. Then, we performed behavioral tests in the corresponding time point, examined brain tissues after hematoxylin-eosin staining to identify changes in cell morphology, and performed immunohistochemical staining and quantitative real-time polymerase chain reaction to detect the expression of NoGo and Nogo receptor (NgR) in brain tissue. RESULTS: For the Neurological Severity Scores of rats, there were obvious differences among the three groups at the corresponding time points. Standard hematoxylin-eosin staining showed that the brain structure of a sham-operated group of rats was clear, uniform, and compact. A TBI group exhibited hemorrhage, edema, inflammatory cell infiltration, condensed nuclei, and necrosis. We also saw glial cells and fibrous tissue proliferation. The α-tocopherol-treated TBI group had similar but less severe changes than the TBI group. Expression of Nogo-A and NgR increased after TBI compared with the sham-operated group. However, Nogo-A and NgR expression was significantly lower in the α-tocopherol-treated TBI group compared with the TBI group. Similarly, results showed that functional neurological deficits among rats in the α-tocopherol-treated TBI group were less pronounced than in the TBI group (model group). CONCLUSIONS: Our data demonstrate that α-tocopherol-treated rats had reduced microscopic evidence of brain damage. Alpha-tocopherol reduced Nogo-A and NgR expression in brain tissue after traumatic brain injury and promoted nerve regeneration. Alpha-tocopherol treatment of TBI rats had a neuroprotective role in their recovery.


Asunto(s)
Química Encefálica/efectos de los fármacos , Lesiones Encefálicas/tratamiento farmacológico , Proteínas de la Mielina/análisis , Receptores de Superficie Celular/análisis , alfa-Tocoferol/uso terapéutico , Animales , Encéfalo/patología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/fisiopatología , Proteínas Ligadas a GPI/análisis , Proteínas Ligadas a GPI/genética , Inmunohistoquímica , Masculino , Proteínas de la Mielina/genética , Fármacos Neuroprotectores/farmacología , Proteínas Nogo , Receptor Nogo 1 , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Receptores de Superficie Celular/genética , alfa-Tocoferol/farmacología
15.
Bioorg Med Chem Lett ; 23(5): 1424-7, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23337602

RESUMEN

Small molecules with oxathiazol-2-one moiety were recently reported as potent inhibitors of Mycobacterium bovis var. bacilli Calmette-Guérin (BCG), among which HT1171 was the most potent and selective proteasome inhibitor. Herein we synthesized a series of novel compounds by bioisosteric replacement of the oxathiazol-2-one ring with 3H-1,2,4-dithiazol-3-one, and also fifteen 1,3,4-oxathiazol-2-one molecules in order for potency comparison and structure-activity relationship elucidation since their antibacterial effects on the virulent strains were not evaluated before. All the compounds were assessed for antitubercular activities on the virulent H37Rv strain by a serial dilution method. Among the tested compounds, 3H-1,2,4-dithiazol-3-one compound 4n was found to be the most active with a lowest MIC(90) value of 1 µg/mL. Furthermore, the cytotoxicities of all the compounds against normal human liver cell line L02 were determined by an MTT method. Compound 4n displayed a lower inhibitory ratio than HT1171 at the concentration of 100 µM, indicating its better safety profile.


Asunto(s)
Antituberculosos/química , Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Tiazoles/química , Tiazoles/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/toxicidad , Antituberculosos/toxicidad , Línea Celular , Humanos , Hígado/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Tiazoles/toxicidad
16.
RSC Adv ; 13(40): 27772-27781, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37731834

RESUMEN

17ß-estradiol is abused in the food industry. Excess 17ß-estradiol can disturb the endocrine system or cause many diseases including obesity, diabetes, cardiac-cerebral vascular disease, and cancers in the human body. A "turn-on" fluorescence resonance energy transfer (FRET) aptasensor based on carbon dots (CDs) and gold nanoparticles (AuNPs) was developed for the detection of 17ß-estradiol. A thiol-modified oligonucleotide was conjugated to AuNPs and amino modified oligonucleotide was linked to CDs. The 17ß-estradiol aptamer was hybridized with the two oligonucleotides, shortening the distance between CDs and AuNPs. With 360 nm UV light excitation, FRET occurred between CDs and AuNPs. The system was "turn-off". When 17ß-estradiol was detected, the aptamer specifically bound to 17ß-estradiol, and the FRET system was destroyed, leading to the "turn-on" phenomenon. The fluorescence intensity recovery was detected in the concentration range of 400 pM to 5.5 µM. The limit of detection (LOD) was 245 pM. The FRET aptasensor demonstrated good selectivity for 17ß-estradiol detection. Reasonable spiked recoveries were obtained in sea salt samples. It showed the potential for estrogen detection in food safety and environmental applications.

17.
Eur J Pharmacol ; 941: 175466, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36528072

RESUMEN

As one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA), interstitial lung disease (ILD) is still challenging due to unrevealed pathophysiological mechanism. To address this question, in the present study, we used the classical collagen-induced arthritis (CIA) mouse model to determine the related-immune mechanism of lung injury and possible pharmacological treatment for RA-ILD. At the peak of arthritis, we found CIA mice developed apparent lung injury, characterized by interstitial thickening, inflammatory cell infiltration, and lymphocyte follicle formation. Additionally, the endothelial injury occurred as the number of endothelial cells (ECs) and their CD31 expression decreased. Along with those, monocytes, predominantly Ly6Chi monocytes with pro-inflammatory phenotype, were also increased. While in the remission period of arthritis, ECs gradually increased with retrieved CD31 expression, leading to decreased infiltrating monocytes, but boosted Ly6Clo population. Ly6Clo monocytes were prone to locate around damaged ECs, promoted ECs proliferation and vascular tube formation, and lessened the expression of adhesion molecules. In addition, we evaluated angiotensin II type 2 receptor (Agtr2), which has been demonstrated to be protective against lung injury, could be beneficial in RA-ILD. We found elevated Agtr2 in CIA lung tissue, and activation of Agtr2, within its specific agonist C21, alleviated the pulmonary inflammation in vivo, reduced ECs injury, and promoted monocytes conversion from Ly6Chi to Ly6Clo monocytes in vitro. Our data reveal a potential pathological mechanism of RA-ILD that involves ECs damage and inflammatory monocytes infiltration and provide a potential drug target, Agtr2, for RA-ILD treatment.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Lesión Pulmonar , Ratones , Animales , Monocitos/metabolismo , Artritis Experimental/patología , Células Endoteliales/metabolismo , Lesión Pulmonar/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Enfermedades Pulmonares Intersticiales/metabolismo , Enfermedades Pulmonares Intersticiales/patología
18.
Front Microbiol ; 14: 1207878, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37614601

RESUMEN

This study used multilocus sequence typing (MLST) to investigate the prevalence of Helicobacter pylori (H. pylori) mixed infections and H. pylori mixed infections involving unrelated strains; and determined the phylogeographic groups of H. pylori recovered from patients in Ningbo, China. A total of 156 H. pylori isolates were obtained from a convenience sample of 33 patients with culture-positive H. pylori infection. MLST was used to classify 150 H. pylori clinical isolates and 12 methodological control strains (6 clinical isolates and 6 strains of American Type Culture Collection H. pylori) into 43 and 12 sequence types (STs), respectively. In this study, 246 new alleles and 53 new STs were identified by MLST. The prevalence of mixed infections was 41% (11/27). The prevalence of H. pylori mixed infections involving unrelated strains was 46% (5/11) and the prevalence of H. pylori mixed infections involving completely unrelated strains (strains with all 7 housekeeping genes different) was 36% (4/11). A phylogenetic tree was created to determine the evolutionary relationships between different strains. The STs in this study were clustered within the hspEAsia subgroup (98%) and hpEurope group (2%). H. pylori mixed infections were common in Ningbo, China. The H. pylori isolates belonging to the hpEurope group were recovered from three different biopsy samples in a native Chinese patient. Most of H. pylori strains colonizing the antrum, corpus, and duodenum bulb were homologous.

19.
Diabetol Metab Syndr ; 14(1): 59, 2022 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-35461267

RESUMEN

BACKGROUND: Acute glycemic variability (GV) has been correlated with the severity of sepsis. The aim of the study was to evaluate the potential association between acute GV and mortality risk in patients with sepsis. METHODS: Cohort studies comparing the risk of death within 3 months between septic patients with higher versus lower acute GV were retrieved by systematic search of Medline, Embase, Web of Science, Wanfang and CNKI databases. We used a random-effect model to pool the data by incorporating the between-study heterogeneity. Sensitivity analyses were performed to evaluate the stability of the findings. RESULTS: Ten studies including 4296 patients were available for the meta-analysis. Pooled results showed that septic patients with higher acute GV had significantly increased mortality risk compared to those with lower acute GV, as evidenced by results using different parameters including standard deviation of blood glucose (SDBG, risk ratio [RR]: 1.74, 95% confidence interval [CI] 1.36-2.24, p < 0.001; I2 = 0%), coefficient of variation of blood glucose (RR: 1.91, 95% CI 1.57-2.31, p < 0.001; I2 = 0%), mean amplitude of glycemic excursion (RR: 1.81. 95% CI 1.36-2.40, p < 0.001; I2 = 0%), and glycemic lability index (RR: 2.52, 95% CI 1.72-3.68, p < 0.001; I2 = 0%). Sensitivity analyses by excluding one study at a time did not significantly affect the results (p all < 0.05). CONCLUSIONS: Higher acute GV may be a predictor of mortality risk in patients with sepsis.

20.
Pain Physician ; 25(4): E609-E617, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35793185

RESUMEN

BACKGROUND: The anterior quadratus lumborum block (QLB) is gaining popularity in total hip arthroplasty (THA) surgeries for postoperative pain management and this technique rarely results in lower limb muscle weakness. However, no studies have described the range of its blockade. OBJECTIVES: The aim of the study was to confirm the range of cold temperature sensory blockades, observe the opioid consumption after THA surgery, assess the pain of the patients, and assess the safety of this technique. STUDY DESIGN: Randomized controlled study. SETTING: Taizhou Hospital of Zhejiang Province. METHODS: Patients who underwent primary THAs were randomized to take an oblique sagittal anterior QLB with 30 mL of 0.375% ropivacaine (QLB+G group) or with 30 mL of 0.9% saline (G group). The main purpose of the study was to confirm the range of cold hypoesthesia. The other aim included the average blood pressure, heart rate, surgical pleth index, and bispectral index values fluctuation during the intraoperative period of expanding the medullary cavity, the sufentanil, and remifentanil consumption during the operation, the amount of time the patients stayed in the Postanesthesia Care Unit, the 8 hours, 16 hours, and 24 hours total dosage of oxycodone, the resting and exercise Visual Analog Scale (VAS) pain scores at 8 hours, 16 hours, and 24 hours after surgery, postoperative adverse events, and safety. RESULTS: The QLB+G group identified areas  of cold hypoesthesia after the block, but there were no areas of cold hypoesthesia in the G group. The consumption of oxycodone in the 8 hours, 16 hours, and 24 hours after the surgery and the consumption of sufentanil during the surgery were significantly smaller in the QLB+G group (P < 0.05). The QLB+G group have lower pain scores at the resting 8 hours and exercise 8 hours, 16 hours, and 24 hours after the surgery (P < 0.05). The 2 groups have comparable safety in the study. LIMITATIONS: This study only tested the areas of cold hypoesthesia after the QLB, but not tested the area of sensory loss. Using ice to test for hypoesthesia is subjective, and may not reflect the actual area of the block. CONCLUSIONS: Ultrasound-guided oblique sagittal anterior QLB can reduce the analgesics required after and during THA and the postoperative VAS pain scores, but it rarely affects muscle strength.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Humanos , Hipoestesia , Oxicodona/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Sufentanilo , Ultrasonografía Intervencional/métodos
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