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1.
J Ethnopharmacol ; 324: 117704, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38176664

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and arthritic pain. Sinomenine (SIN), derived from the rhizome of Chinese medical herb Qing Teng (scientific name: Sinomenium acutum (Thunb.) Rehd. Et Wils), has a longstanding use in Chinese traditional medicine for treating rheumatoid arthritis. It has been shown to possess anti-inflammatory, analgesic, and immunosuppressive effects with minimal side-effects clinically. However, the mechanisms governing its effects in treatment of joint pathology, especially on fibroblast-like synoviocytes (FLSs) dysfunction, and arthritic pain remains unclear. AIM: This study aimed to investigate the effect and underlying mechanism of SIN on arthritic joint inflammation and joint FLSs dysfunctions. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) was induced in rats and the therapeutic effects of SIN on joint pathology were evaluated histopathologically. Next, we conducted a series of experiments using LPS-induced FLSs, which were divided into five groups (Naïve, LPS, SIN 10, 20, 50 µg/ml). The expression of inflammatory factors was measured by qPCR and ELISA. The invasive ability of cells was detected by modified Transwell assay and qPCR. Transwell migration and cell scratch assays were used to assess the migration ability of cells. The distribution and content of relevant proteins were observed by immunofluorescence and laser confocal microscopy, as well as Western Blot and qPCR. FLSs were transfected with plasmids (CRMP2 T514A/D) to directly modulate the post-translational modification of CRMP2 protein and downstream effects on FLSs function was monitored. RESULTS: SIN alleviated joint inflammation in rats with CIA, as evidenced by improvement of synovial hyperplasia, inflammatory cell infiltration and cartilage damage, as well as inhibition of pro-inflammatory cytokines release from FLSs induced by LPS. In vitro studies revealed a concentration-dependent suppression of SIN on the invasion and migration of FLSs induced by LPS. In addition, SIN downregulated the expression of cellular CRMP2 that was induced by LPS in FLSs, but increased its phosphorylation at residue T514. Moreover, regulation of pCRMP2 T514 by plasmids transfection (CRMP2 T514A/D) significantly influenced the migration and invasion of FLSs. Finally, SIN promoted nuclear translocation of pCRMP2 T514 in FLSs. CONCLUSIONS: SIN may exert its anti-inflammatory and analgesic effects by modulating CRMP2 T514 phosphorylation and its nuclear translocation of FLSs, inhibiting pro-inflammatory cytokine release, and suppressing abnormal invasion and migration. Phosphorylation of CRMP2 at the T514 site in FLSs may present a new therapeutic target for treating inflammatory joint's destruction and arthritic pain in RA.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Morfinanos , Sinoviocitos , Ratas , Animales , Fosforilación , Lipopolisacáridos/farmacología , Movimiento Celular , Artritis Reumatoide/patología , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/metabolismo , Citocinas/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Fibroblastos , Dolor/tratamiento farmacológico , Células Cultivadas , Proliferación Celular
2.
Arthritis Res Ther ; 24(1): 277, 2022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-36564853

RESUMEN

BACKGROUND: Rheumatoid arthritis patients usually suffer from arthritic chronic pain. However, due to an incomplete understanding of the mechanisms underlying autoimmune disorders, the management of arthritic pain is unsatisfactory. Here, we investigated the analgesic effect and underlying mechanism of the natural flavonoid naringenin (NAR) in collagen-induced arthritis (CIA) pain. METHODS: NAR was injected (i.p.) once per day for 42 days after initial immunization, and rats were sacrificed on the 28th (the 21st day after final immunization, PID 21) and 42nd days (PID 35). The inflammatory factors, central sensitization indicators, and CRMP2 phosphorylation, as well as the anti-rheumatoid activity and analgesic effect of NAR, were further investigated. RESULTS: We found that NAR decreased the arthritis score and paw swelling, as well as the mechanical and thermal pain. The immunofluorescence results also showed a dose dependent effect of NAR on reducing the expressions of spinal cFos, IBA-1, and GFAP on the 28th (PID 21) and 42nd day (PID 35). NAR decreased the phosphorylation of CRMP2 S522 and the expression of the kinase CDK5 in the spinal dorsal horn, but pCRMP2 Y479 was unchanged. In addition, CRMP2 was co-localized with NEUN, but not IBA-1 or GFAP, indicating the involvement of neural CRMP2 phosphorylation in CIA-related pain. Finally, CRMP2 S522 phosphorylation selective inhibitor (S)-lacosamide also alleviated arthritic pain. CONCLUSIONS: Taken together, our results demonstrate that NAR alleviates inflammation and chronic pain in CIA model, which might be related to its inhibition of neuronal CRMP2 S522 phosphorylation, potentially mitigating the central sensitization. Our study provide evidence for the potential use of NAR as non-opioid-dependent analgesia in arthritic pain.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Dolor Crónico , Ratas , Animales , Fosforilación , Flavonoides/farmacología , Artralgia , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Analgésicos
3.
Front Pain Res (Lausanne) ; 3: 937259, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35959238

RESUMEN

Chronic pain, a common symptom of people with rheumatoid arthritis, usually behaves as persistent polyarthralgia pain and causes serious damage to patients' physical and mental health. Opioid analgesics can lead to a series of side effects like drug tolerance and addiction. Thus, seeking an alternative therapy and screening out the corresponding analgesic drugs is the key to solving the current dilemma. Traditional Chinese Medicine (TCM) therapy has been recognized internationally for its unique guiding theory and definite curative effect. In this study, we used the Apriori Algorithm to screen out potential analgesics from 311 cases that were treated with compounded medication prescription and collected from "Second Affiliated Hospital of Zhejiang Chinese Medical University" in Hangzhou, China. Data on 18 kinds of clinical symptoms and 16 kinds of Chinese herbs were extracted based on this data mining. We also found 17 association rules and screened out four potential analgesic drugs-"Jinyinhua," "Wugong," "Yiyiren," and "Qingfengteng," which were promised to help in the clinical treatment. Besides, combined with System Cluster Analysis, we provided several different herbal combinations for clinical references.

4.
Front Pain Res (Lausanne) ; 3: 946846, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35859655

RESUMEN

Chronic pain is a long-standing unpleasant sensory and emotional feeling that has a tremendous impact on the physiological functions of the body, manifesting itself as a dysfunction of the nervous system, which can occur with peripheral and central sensitization. Many recent studies have shown that a variety of common immune cells in the immune system are involved in chronic pain by acting on the peripheral or central nervous system, especially in the autoimmune diseases. This article reviews the mechanisms of regulation of the sensory nervous system by neutrophils, macrophages, mast cells, B cells, T cells, and central glial cells. In addition, we discuss in more detail the influence of each immune cell on the initiation, maintenance, and resolution of chronic pain. Neutrophils, macrophages, and mast cells as intrinsic immune cells can induce the transition from acute to chronic pain and its maintenance; B cells and T cells as adaptive immune cells are mainly involved in the initiation of chronic pain, and T cells also contribute to the resolution of it; the role of glial cells in the nervous system can be extended to the beginning and end of chronic pain. This article aims to promote the understanding of the neuroimmune mechanisms of chronic pain, and to provide new therapeutic ideas and strategies for the control of chronic pain at the immune cellular level.

5.
Front Cell Dev Biol ; 10: 1041006, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36619869

RESUMEN

Chronic pain is a disease of long-lasting pain with unpleasant feelings mediated by central and (or) peripheral sensitization, its duration usually lasts more than 3 months or longer than the expected recovery time. The patients with chronic pain are manifested with enhanced sensitivity to noxious and non-noxious stimuli. Due to an incomplete understanding of the mechanisms, patients are commonly insensitive to the treatment of first line analgesic medicine in clinic. Thus, the exploration of non-opioid-dependent analgesia are needed. Recent studies have shown that "sinomenine," the main active ingredient in the natural plant "sinomenium acutum (Thunb.) Rehd. Et Wils," has a powerful inhibitory effect on chronic pain, but its underlying mechanism still needs to be further elucidated. A growing number of studies have shown that various immune cells such as T cells, B cells, macrophages, astrocytes and microglia, accompanied with the relative inflammatory factors and neuropeptides, are involved in the pathogenesis of chronic pain. Notably, the interaction of the immune system and sensory neurons is essential for the development of central and (or) peripheral sensitization, as well as the progression and maintenance of chronic pain. Based on the effects of sinomenine on immune cells and their subsets, this review mainly focused on describing the potential analgesic effects of sinomenine, with rationality of regulating the neuroimmune interaction.

6.
Pharmacol Res ; 174: 105955, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34715330

RESUMEN

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).


Asunto(s)
Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos/uso terapéutico , Infectología/tendencias , Medicina Tradicional China/tendencias , SARS-CoV-2/efectos de los fármacos , Antivirales/efectos adversos , COVID-19/diagnóstico , COVID-19/virología , Consenso , Técnica Delphi , Medicamentos Herbarios Chinos/efectos adversos , Medicina Basada en la Evidencia/tendencias , Interacciones Huésped-Patógeno , Humanos , Gravedad del Paciente , SARS-CoV-2/patogenicidad , Resultado del Tratamiento
7.
Front Pharmacol ; 12: 708517, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34489702

RESUMEN

The aim of this study was to investigate the time dependent effects of tetramethylpyrazine (TMP, main activity compound of Ligusticum chuanxiong Hort) on two neurological disorders and their neuropsychiatric comorbidities. 6 Hz corneal rapid kindling was used to induce epileptogenesis and the inflammatory pain was induced by intra-articular Complete Freund's adjuvant (CFA) injection. The mechanical pain thresholds were measured using von Frey hair (D4, D11, D18, D25 after CFA first injection), and the vertical rearings of the mice was observed. To test the neuropsychiatric comorbidities, anxiety-like behaviors of mice were examined by open field and elevated plus maze tests. Two behavioral despair models, tail suspension test and forced swimming test were also used to evaluate the depressive like behaviors. The results showed that TMP administered from the initial day (D1-D35 in kindling model, D0-D14 and D0-D28 in CFA model) of modeling retarded both the developments of 6 Hz corneal rapid kindling epileptogenesis and the CFA induced inflammatory pain. In comparison, late periods administration of TMP (D21-D35 in kindling and D14-D28 in CFA model) showed no effect on the epileptogenesis and the generalized seizures (GS) of kindling, but alleviated maintenance of CFA induced inflammatory pain. Furthermore, we also found all TMP treatments from the initial day of modeling alleviated the co-morbid depressive and anxiety-like behaviors in both models; however, late periods treatments did not, either in kindling or the CFA induced inflammatory pain. BDNF/ERK signaling impairment was also tested by western blot, and the results showed that TMP administered from the initial day of modeling increased the hippocampal BDNF/ERK expression, whereas late period administration showed no effects. Overall, our findings reveal the inconsistent time dependent effects of Tetramethylpyrazine on neurological disorders and their relative neuropsychiatric comorbidities, and provide novel insight into the early application of TMP that might enhance hippocampal BDNF/ERK signaling to alleviate neuropsychiatric comorbidities in neurological diseases.

8.
Chemistry ; 27(60): 14989-14995, 2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34432334

RESUMEN

ZnSe has got extensive attention for high-performance LIBs anode due to its remarkable theoretical capacity and environmental friendliness. Nevertheless, the large volume variation for the ZnSe in the discharge/charge processes brings about rapid capacity fading and poor rate performance. Herein, ZnSe/C hollow polyhedrons are successfully synthesized by selenization of zeolitic imidazolate framework-8 (ZIF-8) with resorcinol-formaldehyde (RF) coating. The protection of C layer derived from RF coating layer and Ostwald ripening during the process of selenization play important roles in promoting formation of ZnSe/C hollow polyhedrons. The ZnSe/C hollow polyhedrons exhibit good rate performance and long-term cycle stability (345 mAh g-1 up to 1000 cycles at 1 A g-1 ) for lithium ion batteries (LIBs) anode. The improved electrochemical performance is benefit from the unique ZnSe/C hollow structure, in which the hollow structure can effectively avoid terrible volume expansion, and the thin ZnSe/C shell can not only provide adequate diffusion paths of lithium ions and but also enhance the electronic conductivity.

9.
Medicine (Baltimore) ; 100(21): e26066, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34032735

RESUMEN

ABSTRACT: Acute-on-chronic hepatitis B liver failure (ACHBLF) is one severe liver disease with rapid progression and high mortality. Identification of specific markers for the prediction of ACHBLF has important clinical significance. We explored the feasibility of UBE2Q1 gene promoter methylation as an early prediction and prognosis biomarker of ACHBLF.UBE2Q1 promoter methylation frequency was detected in 60 patients with acute-on-chronic hepatitis B pre-liver failure (Pre-ACHBLF), 40 patients with chronic hepatitis B and 20 cases of healthy control (HC). The UBE2Q1 mRNA was detected by quantitative real-time polymerase chain reaction.The methylation frequency of the UBE2Q1 promoter in pre-ACHBLF patients was 38.33%, which was significantly lower than that in chronic hepatitis B patients (60.00%) and HCs (65.00%). The UBE2Q1 mRNA expression in pre-ACHBLF patients with UBE1Q1 non-methylation was significantly higher than that in patients with UBE1Q1 promoter methylation. Further analysis showed that hypomethylation of the UBE2Q1 promoter was positively correlated with total bilirubin and international normalized ratio levels in patients with pre-ACHBLF, but negatively correlated with PTA level. COX multivariate analysis showed that the model for end-stage liver disease score and UBE2Q1 promoter hypomethylation status were potential early warning factors that can predict the progression of pre-ACHBLF to ACHBLF. The sensitivity and specificity of UBE2Q1 promoter methylation status combined with the model for end-stage liver disease score for early diagnosis of ACHBLF were 92.9% and 75.0%, respectively. The area under the receiver-operating characteristic curve was 0.895.The hypomethylation of UBE2Q1 promoter is associated with severity of Pre-ACHBLF, which could serve as a potential prognostic biomarker for pre-ACHBLF.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/epidemiología , Hepatitis B Crónica/complicaciones , Enzimas Ubiquitina-Conjugadoras/genética , Insuficiencia Hepática Crónica Agudizada/sangre , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/genética , Adulto , Bilirrubina/sangre , Biomarcadores/análisis , Estudios de Casos y Controles , Metilación de ADN , Estudios de Factibilidad , Voluntarios Sanos , Hepatitis B Crónica/sangre , Humanos , Relación Normalizada Internacional , Pruebas de Función Hepática , Persona de Mediana Edad , Pronóstico , Regiones Promotoras Genéticas/genética , Curva ROC , Medición de Riesgo/métodos , Factores de Riesgo , Índice de Severidad de la Enfermedad
10.
Drug Metab Dispos ; 49(3): 265-275, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33355210

RESUMEN

E7766 represents a novel class of macrocycle-bridged dinucleotides and is under clinical development for immuno-oncology. In this report, we identified mechanism of systemic clearance E7766 and investigated the hepatobiliary transporters involved in the disposition of E7766 and potential drug interactions of E7766 as a victim of organic anion-transporting polypeptide (OATP) inhibitors. In bile-duct cannulated rats and dogs, E7766 was mainly excreted unchanged in bile (>80%) and to a lesser extent in urine (<20%). Sandwich-cultured human hepatocytes (SCHHs), transfected cells, and vesicles were used to phenotype the hepatobiliary transporters involved in the clearance of E7766. SCHH data showed temperature-dependent uptake of E7766 followed by active biliary secretion. In vitro transport assays using transfected cells and membrane vesicles confirmed that E7766 was a substrate of OATP1B1, OATP1B3, and multidrug resistance-associated protein 2. Phenotyping studies suggested predominant contribution of OATP1B3 over OATP1B1 in the hepatic uptake of E7766. Studies in OATP1B1/1B3 humanized mice showed that plasma exposure of E7766 increased 4.5-fold when coadministered with Rifampicin. Physiologically based pharmacokinetic models built upon two independent bottom-up approaches predicted elevation of E7766 plasma exposure when administered with Rifampicin, a clinical OATP inhibitor. In conclusion, we demonstrate that OATP-mediated hepatic uptake is the major contributor to the clearance of E7766, and inhibition of OATP1B may increase its systemic exposure. Predominant contribution of OATP1B3 in the hepatic uptake of E7766 was observed, suggesting polymorphisms in OATP1B1 would be unlikely to cause variability in the exposure of E7766. SIGNIFICANCE STATEMENT: Understanding the clearance mechanisms of new chemical entities is critical to predicting human pharmacokinetics and drug interactions. A physiologically based pharmacokinetic model that incorporated parameters from mechanistic in vitro and in vivo experiments was used to predict pharmacokinetics and drug interactions of E7766, a novel dinucleotide drug. The findings highlighted here may shed a light on the pharmacokinetic profile and transporter-mediated drug interaction propensity of other dinucleotide drugs.


Asunto(s)
Sistema Biliar/metabolismo , Vías de Eliminación de Fármacos/fisiología , Eliminación Hepatobiliar/fisiología , Hígado/metabolismo , Compuestos Macrocíclicos/metabolismo , Fenotipo , Animales , Sistema Biliar/efectos de los fármacos , Perros , Relación Dosis-Respuesta a Droga , Vías de Eliminación de Fármacos/efectos de los fármacos , Interacciones Farmacológicas/fisiología , Predicción , Células HEK293 , Eliminación Hepatobiliar/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Células LLC-PK1 , Hígado/efectos de los fármacos , Compuestos Macrocíclicos/farmacología , Masculino , Ratones , Ratones Transgénicos , Ratas , Ratas Sprague-Dawley , Rifampin/metabolismo , Rifampin/farmacología , Porcinos
11.
Glob Chall ; 3(7): 1800108, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31565386

RESUMEN

Sb2S3 has attracted great research interest very recently as a promising absorber material for photoelectric and photovoltaic devices because of its unique optical and electrical properties and single, stable phase. However, the intrinsic high resistivity property of Sb2S3 material is one of the major factors restricting the further improvement of its application. In this work, the C60 modification of Sb2S3 thin films is investigated. The conductivity of Sb2S3 thin films increases from 4.71 × 10-9 S cm-1 for unmodified condition to 2.86 × 10-8 S cm-1 for modified thin films. Thin-film solar cells in the configuration of glass/(SnO2:F) FTO/TiO2/Sb2S3(C60)/Spiro-OMeTAD/Au are fabricated, and the conversion efficiency is increased from 1.10% to 1.74%.

12.
Cancer Discov ; 8(9): 1176-1193, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29991605

RESUMEN

Mutations in estrogen receptor alpha (ERα) that confer resistance to existing classes of endocrine therapies are detected in up to 30% of patients who have relapsed during endocrine treatments. Because a significant proportion of therapy-resistant breast cancer metastases continue to be dependent on ERα signaling, there remains a critical need to develop the next generation of ERα antagonists that can overcome aberrant ERα activity. Through our drug-discovery efforts, we identified H3B-5942, which covalently inactivates both wild-type and mutant ERα by targeting Cys530 and enforcing a unique antagonist conformation. H3B-5942 belongs to a class of ERα antagonists referred to as selective estrogen receptor covalent antagonists (SERCA). In vitro comparisons of H3B-5942 with standard-of-care (SoC) and experimental agents confirmed increased antagonist activity across a panel of ERαWT and ERαMUT cell lines. In vivo, H3B-5942 demonstrated significant single-agent antitumor activity in xenograft models representing ERαWT and ERαY537S breast cancer that was superior to fulvestrant. Lastly, H3B-5942 potency can be further improved in combination with CDK4/6 or mTOR inhibitors in both ERαWT and ERαMUT cell lines and/or tumor models. In summary, H3B-5942 belongs to a class of orally available ERα covalent antagonists with an improved profile over SoCs.Significance: Nearly 30% of endocrine therapy-resistant breast cancer metastases harbor constitutively activating mutations in ERα. SERCA H3B-5942 engages C530 of both ERαWT and ERαMUT, promotes a unique antagonist conformation, and demonstrates improved in vitro and in vivo activity over SoC agents. Importantly, single-agent efficacy can be further enhanced by combining with CDK4/6 or mTOR inhibitors. Cancer Discov; 8(9); 1176-93. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 1047.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Antagonistas del Receptor de Estrógeno/administración & dosificación , Receptor alfa de Estrógeno/antagonistas & inhibidores , Indazoles/administración & dosificación , Mutación , Administración Oral , Animales , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cisteína/antagonistas & inhibidores , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Antagonistas del Receptor de Estrógeno/química , Antagonistas del Receptor de Estrógeno/farmacología , Receptor alfa de Estrógeno/química , Receptor alfa de Estrógeno/genética , Femenino , Humanos , Indazoles/química , Indazoles/farmacología , Células MCF-7 , Ratones , Conformación Proteica/efectos de los fármacos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Cancer Res ; 77(24): 6999-7013, 2017 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-29247039

RESUMEN

Activation of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a disease with few, if any, effective treatment options. While a number of pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by dose-limiting toxicities mediated by FGFR1-3 receptors. To evade the potential limitations of pan-FGFR inhibitors, we generated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design. Studies in a panel of 40 HCC cell lines and 30 HCC PDX models showed that FGF19 expression is a predictive biomarker for H3B-6527 response. Moreover, coadministration of the CDK4/6 inhibitor palbociclib in combination with H3B-6527 could effectively trigger tumor regression in a xenograft model of HCC. Overall, our results offer preclinical proof of concept for H3B-6527 as a candidate therapeutic agent for HCC cases that exhibit increased expression of FGF19. Cancer Res; 77(24); 6999-7013. ©2017 AACR.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Transformación Celular Neoplásica/genética , Factores de Crecimiento de Fibroblastos/genética , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Int J Biol Macromol ; 93(Pt A): 1155-1160, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27667540

RESUMEN

Using wood pulps with the average degree of polymerization 300-350 and urea as raw materials, cellulose carbamates were successfully synthesized by esterification reaction in N, N-dimethylacetamide(DMAc), an inexpensive, high boiling aprotic and polar solvent, for the purpose of improving the solubility of cellulose, reducing costs and environmental pollution. The products were dissolved in 9% sodium hydroxide solution at a low temperature after washing and drying and the cellulose carbamates solutions were obtained. The solutions were uniformly casted on a glass support after degassing. The regenerated cellulose membranes (CMs) were prepared by immersing the support in coagulation bath for some minutes. The structures of cellulose carbamates were characterized by Fourier transform infrared spectroscopy (FT-IR), 13C solid state nuclear magnetic resonance spectrometry (13C NMR), Thermal gravimetric analysis(TG), Scanning electron microscopy (SEM) and X-ray diffractometry(XRD). The filtration performances of CMs were tested. The results reveal that part groups of cellulose were substituted by amino in the medium, the cellulose carbamates were prepared with the reducing crystallinity and thermal decomposition temperature. The CMs have good separation performance for methylene blue.


Asunto(s)
Carbamatos/química , Celulosa/química , Membranas Artificiales , Hidróxido de Sodio/química , Temperatura , Aguas Residuales/química , Purificación del Agua
15.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(3): 653-6, 2016 Mar.
Artículo en Chino | MEDLINE | ID: mdl-27400499

RESUMEN

Silicon nitride (SiN(x)) films containing nanocrystalline silicon (nc-Si) were deposited on crystalline silicon substrate by facing-target sputtering technique. Thermal annealing process was performed at 450 degrees C for 50 min in a conventional furnace under FG(10% H2, 90% N2) ambient. The photoluminescece (PL) properties of the SiN(x) films with nc-Si were investigated by steady/transient PL spectra measurements by Fluorescence spectrometer with different temperatures. The PL processes could be attributed to the quantum confinement effect of nc-Si and the defects in the film. The PL peak position exhibits a small blue shift with the increasing of the excitation energy, which indicates that the PL portion of the nc-Si increased with smaller size. In addition, the PL lifetime increases and the PL intensity exhibits exponential increase as a result of the decreased temperature which supressed the nonradiative recombination process and then improved the radiative recombination. The PL lifetime of the film significantly reduces with the decreasing of the detection wavelength, which indicates that the PL process related to the the quantum confinement effect strongly depends on temperature.

16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 30(6): 576-80, 2014 Jun.
Artículo en Chino | MEDLINE | ID: mdl-24909276

RESUMEN

OBJECTIVE: To explore the improved immunological responses induced by an amino acid ABC transporter, permease protein PEB1 DNA vaccine primer-protein boost immunization method against Campylobacter jejuni. METHODS: The DNA vaccine pcDNA3.1(-)-PEB1 and protein vaccine were prepared, respectively. The female BALB/c mice were intranasally immunized with the vaccines. PBS and pcDNA3.1(-) were used as controls. The humoral and cellular immunological responses were detected in female BALB/c mice that were challenged by Campylobacter jejuni at 28 days after the final immunization. RESULTS: In the DNA primer-protein boost group at day 56, the stimulation index (SI) of lymphocytes was 2.625±0.275, serum IgG was (2.507±0.124) µg/mL, IL-4 in spleen supernatant was (377.47±14.560) pg/mL, IFN-γ in spleen supernatant was (258.920±13.472) pg/mL, and sIgA in genital tract was (80.351±5.769) ng/mL. All of them were significantly higher than those in controls (P<0.05). The DNA primer-protein boost vaccines induced the strongest levels of protection to BALB/c mice (91.53%). CONCLUSION: The DNA primer-protein boost immunization could induce significant protective immunity against Campylobacter jejuni challenge. It could significantly enhance both humoral and cellular immunologic responses in BALB/c mice, compared with DNA vaccine or protein vaccine immunization alone.


Asunto(s)
Antígenos Bacterianos/inmunología , Infecciones por Campylobacter/inmunología , Campylobacter jejuni/inmunología , Vacunas de ADN/inmunología , Vacunas de Subunidad/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/genética , Antígenos Bacterianos/metabolismo , Western Blotting , Infecciones por Campylobacter/microbiología , Infecciones por Campylobacter/prevención & control , Campylobacter jejuni/fisiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Interacciones Huésped-Patógeno/inmunología , Inmunización/métodos , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-4/inmunología , Interleucina-4/metabolismo , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Bazo/inmunología , Bazo/metabolismo , Vacunas de ADN/administración & dosificación , Vacunas de Subunidad/administración & dosificación
17.
ScientificWorldJournal ; 2014: 653576, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24737985

RESUMEN

Nonthermal plasma technique has drawn extensive attentions for removal of air pollutants such as NO x and SO2. The NO removal mechanism in pulse discharged plasma is discussed in this paper. Emission spectra diagnosis indicates that the higher the discharge voltage is, the more the NO are removed and transformed into O, N, N2, NO2, and so forth. Plasma electron temperature T(e) is ranged from 6400 K at 2.4 kV discharge voltage to 9500 K at 4.8 kV. After establishing a zero-dimensional chemical reaction kinetic model, the major reaction paths are clarified as the electron collision dissociation of NO into N and O during discharge and followed by single substitution of N on NO to form N2 during and after discharge, compared with the small fraction of NO2 formed by oxidizing NO. The reaction directions can be adjusted by N2 additive, and the optimal N2/NO mixing ratio is 2 : 1. Such a ratio not only compensates the disadvantage of electron competitive consumption by the mixed N2, but also heightens the total NO removal extent through accelerating the NO oxidization process.


Asunto(s)
Contaminantes Atmosféricos/química , Óxido Nítrico/química , Nitrógeno/química , Oxidación-Reducción , Oxígeno/química , Temperatura
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(9): 2442-5, 2011 Sep.
Artículo en Chino | MEDLINE | ID: mdl-22097845

RESUMEN

The fluorescence characteristic of various free radical photoinitiators was investigated by fluorescence spectroscopy. The influence of conjugated structure on fluorescence spectrum was analyzed from the molecular structure. The results show that: the wave length of fluorescence excitation spectrum gradually augments with the conjugative effect enhancement, and so does the peak of fluorescence emission spectrum. The transient fluorescence spectrum of photoinitiator is affected by electron groups and the fluorescence decay of photoinitiators with electron-withdrawing groups is faster than that of photoinitiators with electron-donating groups. The excitation peak of photoinitiator has evident red shift with the polarity of solvent increasing, which shows that transition type is pi-pi* transition, and the fluorescence decay is postponed with the solvent glutinosity changing. When the photoinitiator density is at 10(-2) mol x L(-1), the fluorescence decay is evidently fast because of quenching effect caused by self-absorption and collisions between particles.

19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 32(9): 918-23, 2011 Sep.
Artículo en Chino | MEDLINE | ID: mdl-22340883

RESUMEN

OBJECTIVE: To understand the genetic polymorphism of Salmonella and Staphylococcus aureus in Guangdong province, as well as to explore methods for identifying and tracing the source of these two foodborne pathogens. METHODS: Using the automated ribotyping system, two foodborne pathogens were tested with either EcoR I or Pvu II restriction enzymes. BioNumerics software was then applied for image analysis, database establishment and other corresponding analysis. RESULTS: Digestion of 32 Salmonella isolates with Pvu II yielded 19 different ribotypes, and digestion of 14 Salmonella isolates with EcoR I yielded 2 different ribotypes. Staphylococcus aureus isolates showed greater genetic diversity, whereas EcoR I digestion of 49 different isolates yielded 31 different ribotypes. CONCLUSION: Unique Salmonella and Staphylococcus aureus isolates could be identified through ribotyping. Although Salmonella serotyping and ribotyping were not strongly correlated, the combination of both restriction enzymes could be used to more effectively identify the genetic relationship among different strains as well as the source of food poisoning. Thus, not only could the genetic relationships amongst the different strains be inferred through ribotyping skills, the source of food poisoning and mode of transmission could also be determined under the use of this method.


Asunto(s)
Enfermedades Transmitidas por los Alimentos/microbiología , Ribotipificación/métodos , Salmonella/genética , Staphylococcus aureus/genética , Automatización de Laboratorios , China , ADN Bacteriano/genética , Brotes de Enfermedades , Humanos , Salmonella/clasificación , Salmonella/aislamiento & purificación , Serotipificación , Staphylococcus aureus/clasificación , Staphylococcus aureus/aislamiento & purificación
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 29(1): 38-43, 2008 Jan.
Artículo en Chino | MEDLINE | ID: mdl-18785476

RESUMEN

OBJECTIVE: To establish molecular typing of Listeria monocytogenes isolates by pulsed-field gel electrophoresis (PFGE) for studying the epidemiologic characteristics of Listeria monocytogenes isolated from foodstuff in Guangdong province and to build up PFGE typing database of Listeria monocytogenes isolates for identifying the infectious resource of the outbreaks and other epidemiologic investigation. METHODS: "Standardized Protocol for Molecular Subtyping of Listeria monocytogenes by PFGE" was followed. BioNumerics software was applied on image analysis, database establishment, comparative and corresponding analysis. RESULTS: 107 Listeria monocytogenes isolates were typed by PFGE, 41 PFGE types were observed among the isolates. The PFGE types were dispersive among these isolates. Listeria monocytogenes isolates were most frequently isolated in raw chicken while the most PFGE types were found in this type of food. The positive rate was relatively high in cold and iced foods. Only 1-2 DNA fragment difference occurred in 26 Listeria monocytogenes isolates by PFGE, so high degree of relatedness remained among these isolates. There were unique PFGE patterns in the regions of Shaoguan and Huizhou. From time to time, a number of isolates remained close relationship. CONCLUSION: PFGE typing of the 107 Guangdong Listeria monocytogenes isolates demonstrated relative genetic diversity but a number of the isolates showed close relatedness.


Asunto(s)
Electroforesis en Gel de Campo Pulsado/métodos , Listeria monocytogenes/genética , Listeria monocytogenes/aislamiento & purificación , Microbiología de Alimentos , Variación Genética/genética , Genotipo , Listeria monocytogenes/clasificación , Filogenia
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