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1.
Diagn Pathol ; 18(1): 123, 2023 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-37951919

RESUMEN

BACKGROUND: With the continuous discovery of new borderline thyroid lesions and benign and malignant "gray areas", coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. METHODS: In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. RESULTS: Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher. CONCLUSIONS: The results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.


Asunto(s)
Adenoma , Carcinoma Papilar , Disgenesias Tiroideas , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/diagnóstico , Ciclina D1 , Hiperplasia , Diagnóstico Diferencial , Carcinoma Papilar/patología , Biomarcadores de Tumor/metabolismo , Neoplasias de la Tiroides/patología , Adenoma/patología , Disgenesias Tiroideas/diagnóstico
2.
Nat Prod Res ; 35(11): 1869-1873, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31305144

RESUMEN

In the course of searching for cytotoxic metabolites from insects associated actinomyces, two new natural p-terphenyl glycosides, strepantibin D (1) and strepantibin E (2), along with terferol (3), actinomycin D (4), actinomycin V (5) and actinomycin V0ß (6), were identified from the fermentation medium of a Streptomyces sp. which was obtained from the larva body of mud dauber wasp. Strepantibin D (1), previously reported as a synthetic derivative of terfestatin A, is firstly isolated as a natural p-terphenyl in this research. Strepantibin D (1) and terferol (3) showed medium cytotoxic activity against breast cancer cells MCF-7, MDA-MB-231 and BT-474. Actinomycins (4-6), especially actinomycin V (5), displayed remarkable cytotoxicity against breast cancer cells, with IC50 values ranging from 0.83 nM to 369.90 nM.


Asunto(s)
Dactinomicina/farmacología , Streptomyces/química , Compuestos de Terfenilo/farmacología , Avispas/microbiología , Animales , Antineoplásicos/farmacología , Espectroscopía de Resonancia Magnética con Carbono-13 , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dactinomicina/química , Humanos , Larva/microbiología , Compuestos de Terfenilo/química
3.
Mar Drugs ; 17(5)2019 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-31075906

RESUMEN

Four angucycline glycosides were previously characterized from marine-derived Streptomyces sp. OC1610.4. Further investigation of this strain cultured on different fermentation media from that used previously resulted in the isolation of two new angucycline glycosides, vineomycins E and F (1-2), and five known homologues, grincamycin L (3), vineomycinone B2 (4), fridamycin D (5), moromycin B (7), and saquayamycin B1 (8). Vineomycin F (2) contains an unusual ring-cleavage deoxy sugar. All the angucycline glycosides isolated from Streptomyces sp. OC1610.4 were evaluated for their cytotoxic activity against breast cancer cells MCF-7, MDA-MB-231, and BT-474. Moromycin B (7), saquayamycin B1 (8), and saquayamycin B (9) displayed potent anti-proliferation against the tested cell lines, with IC50 values ranging from 0.16 to 0.67 µM. Saquayamycin B (9) inhibited the migration and invasion of MDA-MB-231 cells in a dose-dependent manner, as detected by Transwell and wound-healing assays.


Asunto(s)
Antineoplásicos/farmacología , Glicósidos/farmacología , Antraciclinas/farmacología , Antraquinonas/farmacología , Antineoplásicos/química , Neoplasias de la Mama , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Femenino , Glicósidos/química , Glicósidos/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Estructura Molecular , Streptomyces/metabolismo
4.
J Nat Prod ; 82(5): 1114-1119, 2019 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-31013087

RESUMEN

Two new p-terphenyls, strepantibins A and B (1 and 2), along with the first representative of a naturally occurring bisphenyltropone, strepantibin C (3), were characterized from a Streptomyces sp. associated with the larvae of the mud dauber wasp Sceliphron madraspatanum. Their structures were determined by high-resolution electrospray ionization mass spectrometry, NMR, and X-ray crystallography data interpretation. Strepantibins A-C inhibited hexokinase II (HK2) activity and displayed antiproliferative activity against hepatoma carcinoma cells HepG-2, SMMC-7721 and plc-prf-5. In SMMC-7721 cells treated with strepantibin A, the morphological characteristics of apoptosis were observed.


Asunto(s)
Antineoplásicos/aislamiento & purificación , Inhibidores Enzimáticos/aislamiento & purificación , Hexoquinasa/antagonistas & inhibidores , Streptomyces/química , Avispas/microbiología , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Células Hep G2 , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray
5.
Molecules ; 23(9)2018 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-30227644

RESUMEN

A novel 2'-F,4'-C-OMe⁻arabinouridine (araU) was successfully synthesized and introduced into oligonucleotides. The oligonucleotide containing 2'-F,4'-C-OMe⁻araU exhibited improved nuclease resistance and RNA hybridizing selective ability relative to 2'-F⁻araU. In particular, when 2'-F,4'-C-OMe⁻araU inserted into C⁻H⋯F⁻C bonding-favorable 5'⁻uridine⁻purine⁻3' steps, the modified oligonucleotide showed remarkable binding affinity and selectivity to RNA complements. Thus, 2'-F,4'-C-OMe⁻araU has valuable antisense properties and can be used as novel chemical modification for antisense therapeutic strategy.


Asunto(s)
Oligonucleótidos Antisentido/síntesis química , Oligonucleótidos Antisentido/farmacología , Uridina/síntesis química , Uridina/farmacología , Estabilidad de Enzimas , Desnaturalización de Ácido Nucleico , Oligonucleótidos Antisentido/química , Hidrolasas Diéster Fosfóricas/metabolismo , Venenos de Serpiente/enzimología , Uridina/química
6.
J Zhejiang Univ Sci B ; 19(9): 708-717, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30178637

RESUMEN

otrA resembles elongation factor G (EF-G) and is considered to be an oxytetracycline (OTC)-resistance determinant in Streptomyces rimosus. In order to determine whether otrA also conferred resistance to OTC and other aminoglycosides to Streptomyces coelicolor, the otrA gene from S. rimosus M527 was cloned under the control of the strong ermE* promoter. The resulting plasmid, pIB139-otrA, was introduced into S. coelicolor M145 by intergeneric conjugation, yielding the recombinant strain S. coelicolor M145-OA. As expected S. coelicolor M145-OA exhibited higher resistance levels specifically to OTC and aminoglycosides gentamycin, hygromycin, streptomycin, and spectinomycin. However, unexpectedly, S. coelicolor M145-OA on solid medium showed an accelerated aerial mycelia formation, a precocious sporulation, and an enhanced actinorhodin (Act) production. Upon growth in 5-L fermentor, the amount of intra- and extracellular Act production was 6-fold and 2-fold higher, respectively, than that of the original strain. Consistently, reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that the transcriptional level of pathway-specific regulatory gene actII-orf4 was significantly enhanced in S. coelicolor M145-OA compared with in S. coelicolor M145.


Asunto(s)
Aminoglicósidos/farmacología , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Streptomyces coelicolor/efectos de los fármacos , Antraquinonas/metabolismo , Farmacorresistencia Bacteriana/genética , Streptomyces coelicolor/citología , Streptomyces coelicolor/metabolismo
7.
Bioconjug Chem ; 28(7): 1842-1849, 2017 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-28635259

RESUMEN

Antisense oligonucleotides (ODNs) are therapeutic molecules that hybridize to complementary target mRNA sequences. To further overcome the poor cellular uptake of ODNs, we proposed a novel strategy to deliver ODNs by conjugating the anti-influenza A virus (IAV) ODN with a peptide showing high affinity to the hemagglutinin (HA) on the surface of IAV particles or the IAV-infected host cells. The HA-specific binding peptides were selected by phage display, and the individual binding clones are characterized by DNA sequencing, and the selected phage was further assayed by enzyme-linked immunosorbent assay. The final selected HA-binding peptide, SHGRITFAYFAN, was conjugated to an anti-IAV ODN. The delivery efficiency and the anti-IAV effects of the conjugated molecule were evaluated in a cell-culture and a mouse-infection model. The conjugated molecule was successfully delivered into IAV-infected host cells more efficiently than the anti-IAV ODN in vitro and in vivo. Furthermore, the conjugated molecule protected 80% of the mice from lethal challenge and inhibited the plaque count by 75% compared to the unconjugated molecule (60% and 40%). These findings demonstrate that the delivery of antisense oligodeoxynucleotides to infected tissues by a virus-binding peptide-mediated system is a potential therapeutic strategy against IAV.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Oligonucleótidos Antisentido/uso terapéutico , Animales , Hemaglutininas/metabolismo , Humanos , Inmunoconjugados , Subtipo H1N1 del Virus de la Influenza A/química , Alphainfluenzavirus/química , Ratones , Oligonucleótidos Antisentido/administración & dosificación , Oligonucleótidos Antisentido/inmunología , Biblioteca de Péptidos , Péptidos/metabolismo
8.
Eur J Pharmacol ; 795: 66-74, 2017 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-27916554

RESUMEN

Radiotherapy is one of the most effective non-surgical treatments for many tumors. However, radiation damage remains a major negative consequence of radiotherapy. At present, radio-protective effect of troxerutin has been confirmed, but the mechanism of this radioprotection has not been elucidated. Here, this study showed that troxerutin protected thymus tissue of irradiated mice, and its radio-protective effect on thymocytes was significant in the range of 0.625-10µg/ml. Troxerutin significantly inhibited apoptosis of irradiated thymocytes at the concentration of 10µg/ml. Computer-aided drug design was used to investigate potential candidate targets for troxerutin, and an excellent correlation was identified between troxerutin and AKT (Pharm mapper and KEGG signal pathway). Troxerutin inhibited the activation of PTEN to stimulate AKT, which in turn prevented the activation of JNK to protect cells. Our results showed that troxerutin enhanced radioprotection at least partially by activating AKT to inhibit the activation of JNK.


Asunto(s)
Hidroxietilrutósido/análogos & derivados , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Protectores contra Radiación/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Activación Enzimática/efectos de los fármacos , Activación Enzimática/efectos de la radiación , Hidroxietilrutósido/farmacología , Masculino , Ratones , Timo/efectos de los fármacos , Timo/patología , Timo/efectos de la radiación
9.
Zhongguo Zhong Yao Za Zhi ; 41(21): 4066-4071, 2016 Nov.
Artículo en Chino | MEDLINE | ID: mdl-28929697

RESUMEN

This study aims to analyze the effect of berberine on serum inflammatory factors and carotid atherosclerotic plaques in ppatients with acute cerebral ischemic stroke(AIS). In the study, 120 patients with AIS were randomly divided into berberine group(n=60) and general group (n=60). The 60 cases in the general group were provided with general therapy according to the latest guidelines of diagnosis and treatment of AIS. The berberine group received berberine 300 mg(tid) in addition to the therapy of the general group. The levels of serum inflammatory factors, the nerve function defect grades and the indexes of carotid atherosclerosis plaques [including the total plaque area(TPA), intima-media thickness(IMT) and the number of unstable carotid atherosclerotic plaques] were measured and compared. The results indicated that the levels of serum inflammatory factors, the NIHSS(national institute of health stroke scales) cores and the indexes of carotid atherosclerosis plaques were not significantly different between the berberine groups of general group, with positive correlation between serum inflammatory factors and NIHSS scores(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine groups on 14 d were significantly lower than those on 1 d(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine group on 14 d were significantly lower than those of the general group(P<0.05). The TPA and the number of unstable carotid atherosclerotic plaques of the berberine groups on 90 d were significantly lower than those of general group, with significant differences(P<0.05). The IMT showed a downward trend, but with significant difference.The mRS(modified rankin scale) scores of the berberine group on 90 d were significantly lower, with a higher rate of short-term favorable prognosis (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. This study showed that berberine in addition to the general therapy can significantly lower the levels of serum MIF and IL-6, reduce the degree of carotid atherosclerosis to some extent and improve neurological impairment and the prognosis of patients with AIS.


Asunto(s)
Antiinflamatorios/uso terapéutico , Berberina/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Placa Aterosclerótica/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Grosor Intima-Media Carotídeo , Humanos , Interleucina-6/sangre , Oxidorreductasas Intramoleculares/sangre , Factores Inhibidores de la Migración de Macrófagos/sangre , Factores de Riesgo
10.
Yao Xue Xue Bao ; 51(8): 1271-80, 2016 08.
Artículo en Chino | MEDLINE | ID: mdl-29905991

RESUMEN

Chemical modification is critical for the therapeutic applications of antisense oligonucleotides. Novel 4'-C-MOE and 2'-fluoro- modified monomer 2'-F-4'-C-MOE-ara U and its epimeric 2'-F-4'-C-MOE-r U were synthesized from 2'-fluorinated arabinourine (2'-F-ara U) and 2'-fluorouridine(2'-F-r U), respectively. Their phosphoramidites were synthesized and successfully incorporated into oligodeoxynucleotides. The mismatch discrimination ability of these unnatural monomers and their effect on thermal stability were evaluated in the context of ds DNA and DNA-RNA chimeras. The thermal denaturation studies showed that the incorporation of 2'-F-4'-C-MOE-ara U led to enhanced binding affinity to complementary RNA strand and almost equivalent binding ability to complementary DNA, when compared with 2'-F-4'-C-MOE-r U and 2'-F-ara U modified duplexes. Especially a C-H(…)F-C pseudohydrogen bond was supposed to contribute more binding affinity at uridine-purine steps, meanwhile, 2'-F-4'-C-MOE-ara U had almost the same base discriminatory ability as uridine in ds DNA and DNA-RNA chimeras, while 2'-F-4'-C-MOE-r U was found to have only moderate RNA hybridization ability. However, 2'-F-4'-C-MOE-araU at 3'-end of oligonucleotide could not led to more nuclease hydrolytic stability than that with 2'-F-4'-C-MOE-r U modification. These results demonstrated the feasibility of C4'-MOE modification on 2'-F-ANA and the dramatic effects of the 2'-F substituent, which provides a new approach for further chemical modification of antisense drugs.


Asunto(s)
Oligodesoxirribonucleótidos/química , Oligonucleótidos Antisentido/química , Uridina/química , ADN , Compuestos Organofosforados/síntesis química , ARN
11.
Asian Pac J Cancer Prev ; 15(19): 8171-5, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25339001

RESUMEN

BACKGROUND: To study the radioprotective effects of flavonoids from Rosa roxburghii Tratt (FRT). MATERIALS AND METHODS: The radioprotective effects of FRT were investigated by examining cell viability, 30-day survival of mice and the number of colony-forming units in spleen (CFU-S) after total-body 60Co irradiation. RESULTS: The survival rates of irradiated cells gradually increased with increasing concentrations of FRT. The survival rate was the highest at 87% with a concentration of 30 µg/mL. Pretreatment with FRT was needed to realize its radioprotective activity in mice at the dose of 60 mg/kg. With the increasing doses of 30 mg/kg, 60 mg/kg and 120 mg/kg, the numbers of CFU-S increased, and were significantly different compared with the control group. CONCLUSIONS: Pretreatment with FRT prior to irradiation resulted in significantly higher cell survival at 24 h after 5 Gy radiation, increased 30-day survival in mice after exposure to a potentially lethal dose of 8 Gy, and resulted in a higher number of CFU-S in mice after exposure to a dose of 6 Gy. These results collectively indicate that FRT is an effective radioprotective agent.


Asunto(s)
Flavonoides/farmacología , Rayos gamma , Linfocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Protectores contra Radiación/farmacología , Rosa/química , Bazo/efectos de los fármacos , Animales , Ensayo de Unidades Formadoras de Colonias , Flavonoides/química , Linfocitos/efectos de la radiación , Masculino , Ratones , Extractos Vegetales/química , Protectores contra Radiación/química , Bazo/efectos de la radiación , Tasa de Supervivencia , Irradiación Corporal Total
12.
Asian Pac J Cancer Prev ; 15(18): 7521-6, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25292022

RESUMEN

Radioprotective effects of amentoflavone were investigated by examining cell viability, apoptosis, cell cycling concentrations of intracellular ROS (reactive oxygen species), and relative mitochondrial mass by flow cytometry after 60Co irradiation. Pretreatment with amentoflavone 24 hours prior to 8 Gy 60Co γ-ray irradiation significantly inhibited apoptosis, promoted the G2 phase, decreased the concentration of ROS and mitochondrial mass. These results collectively indicate that amentoflavone is an effective radioprotective agent.


Asunto(s)
Biflavonoides/farmacología , Ciclo Celular/efectos de los fármacos , Rayos gamma , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Protectores contra Radiación/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Ciclo Celular/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Células Cultivadas , Radioisótopos de Cobalto , Cricetinae , Inhibidores del Citocromo P-450 CYP2C9/farmacología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Citometría de Flujo , Pulmón/citología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/efectos de la radiación , Potencial de la Membrana Mitocondrial/efectos de la radiación , Mitocondrias/metabolismo , Mitocondrias/efectos de la radiación
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(12): 3425-31, 2013 Dec.
Artículo en Chino | MEDLINE | ID: mdl-24611416

RESUMEN

The present paper analyzes the sensor's basic principle of the bare tilted fiber Bragg grating (TFBG) and surface plasmon resonance sensor (SPR) that deposited nanoscale gold-coating on the surface of the cladding. We simulated the transmission spectrums and some order cladding mode of TFBG in different concentration solutions by Integration and optical fiber grating software OptiGrating. So by the graphic observation and data analysis, a preliminary conclusion was got that in a certain sensing scope, the cladding modes of TFBG shift slightly to right with the increasing the solution refractive index(SRI),and the relation between resonance peak caused by the coupling of core mode and a certain cladding mode and the SRI was linear. Then the 45 nm thick gold coating was deposited on the surface of the TFBG cladding in a small-scale sputtering chamber KYKY SBC-12, and thermal field scanning electron microscopy presents that the effect of gold-coating was satisfactory to a certain extent in terms of microscopic level. The refractive index(RI) sensing experiments of different concentration solutions of NaCI, MgCI2, CaCI2 were carried out using bare and gold deposited TFBG. The RI sensing characteristics of both bare and gold deposited TFBGs respectively were studied by experiments. Meanwhile, it proved the conclusion that the cladding modes of TFBG drifted to right gradually when the SRI was increasing and the relations between resonance peak caused by the coupling of core mode and a certain cladding mode and the SRI were linear. And by quantitative analysis, we know that SPR sensor with the deposited namoscale gold layer on the surface of cladding enhanced the RI sensitivity dramatically by 2 to 500 nm RIU-1 which is 200 to 300 times larger than that of the bare tilted fiber Bragg grating approximately. The degrees of linear fittings of resonance peak caused by the coupling of core mode and a certain cladding mode and SRI of bare and gold-coating deposited SPR sensor are very good and both of them reach up to more than 0. 99.

14.
Asian Pac J Allergy Immunol ; 30(3): 209-13, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23156851

RESUMEN

BACKGROUND: Few data on the effect of antihistamines on patch test results in Chinese patients are currently available. OBJECTIVES: To evaluate the effect of desloratadine on patch test reactions. METHODS: Patients known to have at least one strongly positive (+ +) test with an allergen were re-patch tested after 14 to 70 days (average time interval 26.3 days) of administering oral desloratadine 5 mg twice a day for 5 days before and during the test. Patch testing was performed with the previously recognized allergen according to the guidelines of the ICDRG. The -to + + + system was converted into numeric values (0, 1, 2, 3, 4) for statistic evaluation. RESULTS: Of the 58 chambers (47 patients), which were all strongly positive (+ +) during the 1st patch test, the situation was unchanged in 51 chambers; 4 + reactions and 2 + + + reactions were observed; and 1 chamber was negative. There was no statistically significant difference when comparing the scores of the 1st assessment with those of the 2nd (p = 0.206). If the patch test reaction of the patient who dropped out of the trial had changed from strongly positive (+ +) to negative, there would still have been no statistically significant difference between the score of the 1st assessment with those of the 2nd ( p = 0.107). CONCLUSIONS: The reaction of a patch test is not hampered by doubling dose of desloratadine. The anti-inflammatory effects of desloratadine on patch test reaction may be limited.


Asunto(s)
Alérgenos/inmunología , Antiinflamatorios/farmacología , Antagonistas de los Receptores Histamínicos H1 no Sedantes/farmacología , Loratadina/análogos & derivados , Pruebas del Parche/métodos , Adulto , Antiinflamatorios/inmunología , Pueblo Asiatico , Femenino , Antagonistas de los Receptores Histamínicos H1 no Sedantes/inmunología , Humanos , Loratadina/inmunología , Loratadina/farmacología , Masculino
15.
Anal Bioanal Chem ; 403(5): 1333-42, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22441199

RESUMEN

A simple and rapid ion-pair reversed phase high-performance liquid chromatography (IP-RP-HPLC) method was developed to analyse the major impurities of lipophilic-conjugated phosphorothioate oligonucleotides (ODNs), which provided better separation performance than capillary gel electrophoresis and ion exchange chromatograph methods. The study showed that covalent conjugations of lipophilic group (docosanyl, C(22)) to ODN at 5'-termini (denoted as 5'C(22)-Flu) or 3'-termini (denoted as 3'C(22)-Flu) exhibited similar chromatographic retention behavior. Some important analytical conditions of IP-RP-HPLC, including column type, ion-pairing buffer composition, and separation temperature, were investigated for the effects on the separation of crude 5'C(22)-Flu. As expected, the method developed was successfully applied to the analysis of crude 3'C(22)-Flu and both purified products. Furthermore, the related impurities derived from the synthetic process were identified by matrix-assisted laser desorption-ionization time-of-flight mass spectrum. These MS results are of benefit to understanding the major process-related impurities in lipophilic-ODN conjugates synthesis, thereby elevating the quality of target products.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Fase Inversa/métodos , Oligonucleótidos Fosforotioatos/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Oligonucleótidos Fosforotioatos/síntesis química
16.
Zhong Yao Cai ; 32(4): 571-4, 2009 Apr.
Artículo en Chino | MEDLINE | ID: mdl-19645245

RESUMEN

OBJECTIVE: To observe the antitussive and antiasthmatic effects of Radix Fici Hirtae (RFH). METHODS: Antitussive effects were observed by ammonia water steaming test in mice and by citric acid test in guinea pigs. Antiasthmatic actions in guinea pigs were observed by histamine and acetylcholine ultrasonic atomization test, involved isolated guinea pig tracheal smoth muscle experiment and anaphylactic shock of guinea pigs. RESULTS: RFH decreased the frequency of cough induced by ammonia in mice and by citric acid in guinea pig, prolonged the latent period of cough and inhibited the experimental asthma by histamine and acetylcholine solution in conscious guinea pigs, antagonisted the contraction of tracheal smooth muscle by histamine phosphate in guinea pigs and could compete anaphylactic shock in guinea pigs. CONCLUSION: RFH has obvious antitussive and antiasthmatic effects.


Asunto(s)
Antitusígenos/uso terapéutico , Tos/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Expectorantes/uso terapéutico , Moraceae , Acetilcolina/administración & dosificación , Anafilaxia/inducido químicamente , Anafilaxia/tratamiento farmacológico , Animales , Antitusígenos/administración & dosificación , Antitusígenos/farmacología , Asma/inducido químicamente , Asma/tratamiento farmacológico , Astragalus propinquus/química , Ácido Cítrico/administración & dosificación , Tos/inducido químicamente , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Expectorantes/administración & dosificación , Expectorantes/farmacología , Femenino , Cobayas , Histamina , Masculino , Ratones , Moraceae/química , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Fitoterapia , Raíces de Plantas/química , Distribución Aleatoria , Tráquea/efectos de los fármacos
17.
Artículo en Inglés | MEDLINE | ID: mdl-19131282

RESUMEN

A novel biological sample clean-up procedure has been developed for the determination of phosphorothioate oligodeoxynucleotides (PS-ODNs) and derived metabolites in biological fluids (plasma, urine and bile) and in tissues and feces from mice and rats. This method uses a one-step C18 solid-phase extraction (SPE) for biological matrix removal, and it uses capillary gel electrophoresis (CGE) for analyte detection. The assay is specific, and its linearity is superb (r>0.99) for IV-AS (a 13-mer PS-ODN) and PS19 (a 19-mer PS-ODN) in a variety of biological matrices. For both IV-AS and PS19, the precision, accuracy and absolute recovery values were found to be <20%, +/-20% and 80-120%, respectively. The LODs of IV-AS and PS19 were 0.6 mg/l for plasma, 0.8 mg/l for rat urine and bile, 6 microg/g for rat tissues, and 10 microg/g for rat feces, with a signal-to-noise ratio of 3 (S/N=3). This method has been successfully applied to the analysis and quantitation of PS-ODNs in various biological samples arising from preclinical pharmacokinetic studies.


Asunto(s)
Líquidos Corporales/química , Electroforesis Capilar/métodos , Heces/química , Oligodesoxirribonucleótidos/análisis , Compuestos Organofosforados/análisis , Tionucleótidos/análisis , Acetonitrilos/química , Animales , Secuencia de Bases , Ratones , Oligodesoxirribonucleótidos/farmacocinética , Compuestos Organofosforados/farmacocinética , Ratas , Estándares de Referencia , Sensibilidad y Especificidad , Cloruro de Sodio/química , Tionucleótidos/farmacocinética , Distribución Tisular
18.
Immunology ; 121(4): 545-54, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17428310

RESUMEN

Although it is clear that the CD45 tyrosine phosphatase is required for efficient T-cell activation and T-cell development, the factors that regulate CD45 function remain uncertain. Previous data have indicated that there is an association of CD45 with CD4 and the T-cell receptor (TCR) complex controlled by the variable ectodomain of CD45 and, following activation, by high- and low-potency peptides. This suggests that controlling substrate access to CD45 may be an important regulatory mechanism during T-cell activation. In the present study we have examined the role of the transmembrane adapter-like molecule CD45-associated protein (CD45-AP) in regulating the association of CD45 with CD3/TCR and lck, and in regulating primary CD4(+) T-lymphocyte activation. In CD4(+) T cells from CD45-AP-deficient mice, coimmunoprecipitation of CD45 with the CD3/TCR complex, in addition to lck, is significantly reduced compared with wild-type T cells. Functionally, this correlates with a decreased proliferative response, a decrease in interleukin (IL)-2 production, and a decrease in calcium flux upon stimulation with a low-potency altered peptide ligand. However, the response of CD45-AP-deficient T cells to stimulation with a high-avidity agonist peptide was largely intact, except for a modest decrease in IL-2 production. These data suggest that CD45-AP promotes or stabilizes the association of CD45 with substrates and regulates the threshold of T-cell activation.


Asunto(s)
Complejo CD3/inmunología , Linfocitos T CD4-Positivos/inmunología , Péptidos y Proteínas de Señalización Intracelular/inmunología , Activación de Linfocitos/inmunología , Proteínas de la Membrana/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Proteínas Adaptadoras Transductoras de Señales/inmunología , Animales , Antígenos CD28/inmunología , Calcio/metabolismo , Proliferación Celular , Células Cultivadas , Interleucina-2/biosíntesis , Ratones , Ratones Transgénicos
19.
Anal Biochem ; 345(1): 81-9, 2005 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-16102718

RESUMEN

A protocol relying on Sanger sequencing reactions in combination with mass spectrometry (MS) for sequence confirmation of antisense phosphorothioate oligodeoxynucleotides is described. In this procedure, synthetic phosphorothioate oligodeoxynucleotides are used as reverse primers for extension of matched templates with enough length (approximately 150-300 bp) for well-established Sanger sequencing. Because the complementary strand of modified primer is used directly for sequencing primer extension, the base order shown in the sequencing result is reversely complementary to phosphorothioate oligodeoxynucleotide. This sequencing method can be applied not only to phosphorothioate oligodeoxynucleotides with different lengths (13-21 mer) and base composition but also to sequences with bases' switch, deletion, or insertion. In addition, modified primers incorporate the 5' end of polymerase chain reaction (PCR) products conveying the characters of phosphorothioate modification. The method requires only common reagents and instruments and so is better suited to routine sequence analysis in quality control of phosphorothioate antisense drugs.


Asunto(s)
Oligodesoxirribonucleótidos/química , Análisis de Secuencia de ADN , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Tionucleótidos/química , Secuencia de Bases , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/métodos , Análisis de Secuencia de ADN/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
20.
Analyst ; 130(4): 474-82, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15776156

RESUMEN

In this study several SARS-CoV structural proteins and fragments were expressed in E. coli as GST or TRX fusion proteins. They were fabricated on a microarray and tested with sera from SARS patients. Antigenic screening indicated that recombinant GST-N2 fusion protein, the carboxy-terminus 213aa-423aa of N protein, was strongest positive and weakest non-specific compared with others. An indirect antibody ELISA method was developed and clinical positive and negative sera for their antibodies against GST-N2 fusion protein were assayed. 311 out of the 442 sera from clinical SARS inpatients, as well as 229 out of 302 sera from convalescent patients gave positive reactivities; positive rates were 70.4% and 75.8% respectively. Sera from a total of 2726 non-SARS patients and healthy individuals were tested and the false positive rate was only 0.07%. When the sensitivity control sample was diluted 1 : 64, it yielded OD values above the cutoff value. Reported data showed that this was a relatively high degree of sensitivity and specificity for SARS-CoV antibody testing. The data indicate that GST-N2 fusion protein, which was screened by protein microarray, may be a valuable diagnostic antigen for the development of serological assays for SARS. In addition, protein microarray assay presents a higher positive rate and sensitivity (86.1% and 1 : 200) compared with the traditional ELISA screening method, and could provide a rapid, parallel and high-throughput antigen screening platform.


Asunto(s)
Anticuerpos Antivirales/análisis , Análisis por Matrices de Proteínas , Síndrome Respiratorio Agudo Grave/diagnóstico , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Antígenos Virales/aislamiento & purificación , Reactores Biológicos , Estudios de Casos y Controles , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática/métodos , Escherichia coli , Humanos , Inmunoglobulina G/análisis , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana , Transportadores de Anión Orgánico/genética , Proteínas Recombinantes de Fusión/análisis , Sensibilidad y Especificidad , Síndrome Respiratorio Agudo Grave/virología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
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