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1.
Nutrients ; 14(5)2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35267905

RESUMEN

In recent years, multiple edible polysaccharides from Codonopsis pilosula were mainly isolated with high average molecular weights and exhibited various bioactivities, but it was proven that low-molecular-weight polysaccharides could exert stronger activities due to the superior water solubility and permeability. In the present study, the water-soluble polysaccharide C. pilosula with low molecular weight was isolated under ultrasonic assistance at 30 °C, the extraction process was optimized via response surface method (RSM), and the structure and immunoregulatory activity were further investigated. The maximum yield (4.86%) for crude polysaccharides (cCPPs) was obtained under following parameters: ultrasonic power of 370 W, liquid/material ratio of 33 mL/g, ultrasonic time of 81 min. Subsequently, the cCPPs were further purified through dialysis and Sephadex G-25 column to acquire purified polysaccharide (CPPs). Structural analysis indicated that CPPs was a glucofructan (average molecular weight of 4.23 × 103 Da) with (2→1)-ß-D-Fruf and (1→)-α-D-Glcp as the backbone branched by (2→6)-ß-D-Fruf. Additionally, CPPs could enhance immunoregulatory function by stimulating NO production and cytokine (IL-6 and TNF-α) secretion of RAW264.7 macrophages dose-dependently, which presented no cytotoxic effects. These data suggest that CPPs have the potential to be used as a nutritional dietary compound and natural immunostimulant supplement in the food industry.


Asunto(s)
Codonopsis , Codonopsis/química , Fructanos/farmacología , Glucosa/análogos & derivados , Diálisis Renal , Ultrasonido
2.
Int J Ophthalmol ; 15(2): 306-311, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35186692

RESUMEN

AIM: To evaluate the ophthalmic manifestations, radiographic features, and prognosis of Chinese patients with primary orbital mesenchymal chondrosarcoma (MCS). METHODS: The study included 6 cases with primary orbital MCS treated at Tianjin Eye Hospital from January 2009 to December 2019. Patitent ophthalmic manifestations, radiographic features, diagnosis, pathology, therapeutic regimens, and prognosis were retrospectively reviewed. RESULTS: Six patitents with primary orbital MCS were identified. The mean age at the first visit was 33y (range, 25-42y). All six patients displayed manifestations of exophthalmos, diplopia, limitation of eye displacement, upper eyelid oedema, decreased visual acuity and ptosis. The mean disease history and range were 5 and 2-8mo, respectively. The tumors were located in the superonasal extraconal compartment (2/6, 33.3%), intraconal compartment (2/6, 33.3%), and bitemporal extraconal compartment (2/6, 33.3%), respectively. Radiographic features were a well-defined, orbital mass with calcification and ossification on computed tomography (CT), and marked heterogenous enhancement on dynamic magnetic resonance imaging (MRI). Five patients were treated with tumor resection and one patient received orbital exenteration. Five patients in the cohort received postoperative radiation therapy, two patients received chemotherapy, and one patient did not receive postoperative adjuvant therapy because he refused. The histopathologic classification revealed a tumour composed of a mixture of mature chondroid tissue surrounded by small, round, and undifferentiated mesenchymal cells. Immunohistochemistry revealed Bcl-2, vimetin, CD99, and S-100 were expressed were expressed. After surgeries, two patients have developed a local recurrence. The median recurrence time of 58mo (52-64mo). One patient had distant recurrence included the lungs occurred 52mo after the initial surgery. CONCLUSION: The possibilty of orbital MCS need to be considered when a painless, slowly growing orbital mass with calcification and ossification. From our experience, trimodality treatment of radiation therapy, chemotherapy and surgery maybe the best option. Orbital MCS has a high tendency for late recurrence, regular long-term follow-up after complete excision is mandatory.

3.
Front Endocrinol (Lausanne) ; 12: 759597, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34867801

RESUMEN

Mutations in CD40 have been widely reported to be risk factors for Graves' disease (GD). The gene, along with its cognate ligand CD40L, may regulate pro-inflammatory and immune responses. Rs1883832, located at the -1 position of the Kozak sequence, is the most well-studied single nucleotide polymorphism (SNP) of CD40, and has been confirmed to predispose those with the alteration to GD, regardless of ethnicity. Our genome-wide association study (GWAS) indicated that several SNPs, including rs1883832 located within the vicinity of CD40 were associated with GD in the Han Chinese population. Aiming at identifying the most consequential SNP and its underlying pathogenic mechanism, we performed a two-stage refined study on 8,171 patients with GD and 7,906 controls, and found rs1883832 was the most significantly GD-associated SNP in the CD40 gene region (PCombined = 9.17×10-11, OR = 1.18). Through searching the cis-expression quantitative trait locus database and using quantitative RT-PCR, we further discovered that the rs1883832 genotype can influence CD40 gene transcription. Furthermore, we demonstrated that rs1883832 is a susceptibility locus for pTRAb+ GD patients. In conclusion, the current study provides robust evidence that rs1883832 can regulate CD40 gene expression and affect serum TRAb levels, which ultimately contributes to the development of GD.


Asunto(s)
Antígenos CD40/genética , Enfermedad de Graves/genética , Pueblo Asiatico/genética , Cromosomas Humanos Par 20 , Estudios de Cohortes , Femenino , Humanos , Masculino , Polimorfismo de Nucleótido Simple
4.
Int J Ophthalmol ; 14(9): 1384-1391, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34540614

RESUMEN

AIM: To evaluate the application of anterior segment-optical coherence tomography (AS-OCT) in posterior capsule opacification (PCO) severity assessment and analyse the relationship between PCO severity and intraocular lens (IOL) characters. METHODS: PCO patients were prospectively recruited. Cross-sectional images of the anterior segment at horizontal and vertical meridians were acquired with AS-OCT. The area of the IOL-PC (posterior capsular) space and PCO severity (area, thickness, and density at 3 mm and 5 mm IOL optic regions) were measured. The relationship between PCO severity and visual acuity, comparisons of PCO severity and IOL-PC space using varied IOL designs were analysed. RESULTS: One hundred PCO eyes were enrolled. IOL-PC space, PCO thickness and area were positively correlated with axial length. In addition, PCO area and thickness were positively correlated with visual acuity when it was ≤0.52 logMAR. The cut-off level of visual acuity should be 0.52 logMAR. With varied IOL designs, 3-piece C haptic IOL showed a smaller PCO area and thickness than the 1-piece 3 haptic IOL and 1-piece 4 haptic IOL. PCO area and thickness values for an IOL with a diameter ≤11.0 mm was greater than for an IOL with a diameter of 12.5 mm, and the differences were statistically significant. PCO area and thickness increased when IOL haptic angulation increased (from 0 to 12 degrees). CONCLUSION: In PCO eyes, cut-off level of visual acuity is 0.52 logMAR. With more severe PCO, visual acuity maybe not enough to describe the visual function impairment. PCO severity and IOL-PC space are significantly correlated with axial length and IOL design and material.

5.
J Med Syst ; 45(4): 42, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33608811

RESUMEN

In confronting the sudden epidemic of COVID-19, China and other countries have been under great deal of pressure to block virus transmission and reduce death cases. Fangcang shelter hospital, which is converted from large-scale public venue, is proposed and proven to be an effective way for administering medical care and social isolation. This paper presents the practice in information technology support for a Fangcang shelter hospital in Wuhan, China. The experiences include the deployment strategy of IT infrastructure, the redesign of function modules in the hospital information system (HIS), equipment maintenance and medical staff training. The deployment strategy and HIS modules have ensured smoothness and efficiency of clinical work. The team established a quick response mechanism and adhered to the principle of nosocomial infection control. Deployment of network and modification of HIS was finished in the 48 hours before patient admittance. A repair hotline and remote support for equipment and software were available whenever medical workers met with any questions. No engineer ever entered the contaminated areas and no one was infected by the coronavirus during the hospital operation. Up to now, Fangcang shelter hospital is adopted by many regions around the world facing the collapse of their medical systems. This valuable experience in informatization construction and service in Wuhan may help participators involving in Fangcang shelter hospital get better information technology support, and find more practical interventions to fight the epidemic.


Asunto(s)
COVID-19/terapia , Refugio de Emergencia/organización & administración , Hospitales Especializados/organización & administración , Unidades Móviles de Salud/organización & administración , Aislamiento de Pacientes/estadística & datos numéricos , COVID-19/epidemiología , China , Urgencias Médicas , Arquitectura y Construcción de Instituciones de Salud , Hospitales de Aislamiento , Humanos , Tecnología de la Información , Factores de Riesgo
6.
Glycoconj J ; 38(1): 13-24, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33507460

RESUMEN

A novel cold-water-soluble polysaccharide (BEP), with a molecular weight of 6.0 × 106 Da, was isolated from Boletus edulis. BEP consists of galactose, glucose, xylose, mannose, glucuronic, and galacturonic acid in a ratio of 0.34:0.28:0.28:2.57:1.00:0.44. The IR results showed that BEP was an acid polysaccharide, containing α-type and ß-type glucoside bonds. MTT assay showed BEP could inhibit cell proliferation significantly. Morphological observation demonstrated that BEP-treated MDA-MB-231 and Ca761 cells exhibited typical apoptotic morphological features. Flow cytometry analysis revealed that BEP caused mitochondrial membrane potential collapse. Annexin V-FITC/PI staining indicated that BEP induced apoptosis of MDA-MB-231 and Ca761 cells through cell block in S phase and G0/G1 phase, respectively. Western blot results showed that BEP could increase the Bax/Bcl-2 ratios, promote the release of cytochrome C, and activate the expression of caspase-3 and caspase-9 in MDA-MB-231 and Ca761 cells. In conclusion, our results demonstrated that BEP could inhibit the proliferation of breast cancer cells and induce apoptosis through mitochondrial pathways.


Asunto(s)
Antineoplásicos/farmacología , Basidiomycota/química , Neoplasias de la Mama/tratamiento farmacológico , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proteína 5 Relacionada con la Autofagia/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Polisacáridos Fúngicos/aislamiento & purificación , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Peso Molecular , Monosacáridos/análisis , Especies Reactivas de Oxígeno/metabolismo , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier
8.
J Integr Med ; 18(4): 319-325, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32532615

RESUMEN

OBJECTIVE: Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC), and Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) Granule, a compound of traditional Chinese herbal medicine, side-by-side with sorafenib for the treatment of advance HCC. METHODS: Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process. RESULTS: Of the 325 patients included, 161 received JD Granule and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83-9.47) in the group receiving JD Granule and 8 months (95% CI: 6.67-9.80) in the group receiving sorafenib, with half-, 1- and 2-year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD Granule group (9.03 months; 95% CI: 6.37-14.2) and the sorafenib group (7.93 months; 95% CI: 6.5-9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD Granule group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD Granule was more cost-effective than sorafenib treatment for advanced HCC. CONCLUSION: Compared to sorafenib, JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Medicamentos Herbarios Chinos , Neoplasias Hepáticas , Sorafenib , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Estudios Prospectivos , Sorafenib/uso terapéutico
9.
Carbohydr Polym ; 240: 116323, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32475583

RESUMEN

A new water-soluble polysaccharide, CMP90, with a molecular weight of 23.9 kDa was isolated from Castanea mollissima Blume and the preliminary structural characteristics and antitumor effects of CMP90 in vitro and in vivo were investigated in the research. CMP90 consists of arabinose, galactose, glucose, xylose and mannose (molar ratio: 0.08:0.11:5.14:0.12:0.08) with α- and ß-anomeric units. The results of in vitro experiments indicated that CMP90 exhibited a significant inhibitory effect on the proliferation of HL-60 cells with typical apoptotic characteristics by inducing cell cycle arrested at G1/M phase. Additionally, the results in vivo suggested CMP90 was able to inhibit the growth of S180 solid tumors via protecting immune organs, improving the levels of serum cytokines (TNF-α, IL-2 and IFN-γ), enhancing the activities of immune cells (macrophages, lymphocytes and NK cells) and inducing cell apoptosis or death. Taken together, these combined data clearly indicated that CMP90 may be used as a potential candidate agent for cancer therapy.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Fagaceae/química , Polisacáridos/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Células HL-60 , Humanos , Células Asesinas Naturales/efectos de los fármacos , Linfocitos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Relación Estructura-Actividad , Células Tumorales Cultivadas
10.
J Clin Endocrinol Metab ; 105(7)2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32246145

RESUMEN

CONTEXT: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the 2 main autoimmune thyroid diseases that have both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these closely related diseases. OBJECTS: To identify the susceptibility genes for HT in the Chinese cohort and compare susceptibility genes between GD and HT. DESIGN: In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2682 patients with HT, 4980 patients with GD, and 3892 controls. The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS, with the logistic regression analysis adjusted for sex and age. RESULTS: We identified 11 susceptibility loci for HT in the Chinese Han population, with 4 loci, including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in HLA-B, and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5 × 10-8. Five loci were reported to be associated with HT for the first time. We also identified 6 susceptibility loci with heterogeneity between GD and HT. Out of them, 4 loci were associated with GD but not with HT, including HLA-DPB1, CD40, TSHR, and TG; the association of HLA-B with GD was stronger than that with HT, but the association of SLAMF6 was reversed. CONCLUSION: Our findings suggested that the pathogenesis of HT and GD was different.


Asunto(s)
Sitios Genéticos , Predisposición Genética a la Enfermedad , Enfermedad de Graves/genética , Enfermedad de Hashimoto/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Antígeno CTLA-4/genética , China , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Antígenos HLA-B/genética , Humanos , Masculino , Persona de Mediana Edad , Receptores Acoplados a Proteínas G/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética
11.
Bioorg Chem ; 97: 103701, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32146174

RESUMEN

In this study, human lung cancer SPC-A-1 cells were cultured with Seleno-Chitosan to study the mechanism of apoptosis. CCK-8 results showed that with the increase of the concentration of Seleno-Chitosan and the prolongation of culture time, the inhibition on the proliferation of SPC-A-1 cells gradually increased, and the morphology of SPC-A-1 cells changed obviously. Flow cytometry result suggested that the concentration of calcium ion, level of reactive oxygen species and mitochondrial membrane potential increased. Western blot showed that Seleno-Chitosan induced apoptosis via the mitochondrial pathway in SPC-A-1. Eventually, we found 15 proteins that were expressed abnormally by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), which were all related to Fas/FasL pathway of cells.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Quitosano/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos de Organoselenio/farmacología , Transducción de Señal/efectos de los fármacos , Antineoplásicos/química , Línea Celular Tumoral , Quitosano/análogos & derivados , Proteína Ligando Fas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Compuestos de Organoselenio/química , Receptor fas/metabolismo
12.
Int J Ophthalmol ; 11(11): 1835-1841, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30450316

RESUMEN

AIM: To describe the histopathologic and clinical features of eyelid tumor cases from Tianjin Eye Hospital during 2002 to 2015. METHODS: In this retrospective study, a total of 2228 cases of eyelid tumors with pathologic diagnoses were enrolled. The eyelid tumors were classified into three groups according to tumor origin: epidermal, adnexal and miscellaneous, including melanocytic, neural and vascular lesions. Inflammatory tumor-like lesions were excluded. The clinical characteristics of the eyelid tumors were analyzed, including age, gender and lesion location. RESULTS: Most eyelid tumors were epidermal in origin (1080, 48.5%), followed by miscellaneous (885, 39.7%) and adnexal tumors (263, 11.8%). Among all the tumors, 292 (13.1%) were malignant lesions, 1910 (85.7%) benign and 26 (1.1%) premalignant lesions. Most malignant tumors originated from epidermal cells (60.0%), followed by adnexal cells (34.6%). The most common malignant tumors were basal cell carcinomas (56.5%) followed by sebaceous carcinoma (34.6%), squamous cell carcinomas (3.8%) and lymphoma/plasmocytoma (1.7%). The benign and premalignant eyelid lesions mostly originated from epidermal cells (46.4%) followed by miscellaneous cell sources (45.2%), including melanocytic nevus (33.8%), seborrheic keratosis (13.7%), squamous cell papilloma (13.0%) and epidermal cysts (11.5%). CONCLUSION: Eyelid tumors are mostly epithelial in origin. Benign tumors are significantly more common than malignant tumors with an obvious female predominance, and the most frequent malignant tumor are basal cell carcinoma, sebaceous carcinoma and squamous cell carcinomas. The tumor clinical features varied among the different subtypes.

13.
Int J Ophthalmol ; 10(11): 1703-1709, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29181314

RESUMEN

AIM: To determine the repeatability of Ophtha Top topography and assess the consistency with intraocular lens (IOL)-Master and LenstarLS900 (Lenstar) in measuring corneal parameters among cataract patients. METHODS: Totally 125 eyes were enrolled. Corneas were successively measured with Ophtha Top, IOL-Master and Lenstar at least three times. The flattest meridian power (Kf), the steepest meridian power (Ks), mean power (Km), J0 and J45 were recorded. Intra-class correlation coefficients (ICCs), the coefficient of variance (COV), within subject standard deviation (Sw), and test-retest repeatability (2.77Sw) were adopted to determine the repeatability. The 95% limit of agreement (95%LOA) and Bland-Altman plots were used to assess comparability. RESULTS: Repeatability of Ophtha Top topography for measuring corneal parameters showed the ICCs were all above 0.93, 2.77Sw was lower than 0.31, and the COV of the Kf and Ks was lower than 0.25. The keratometric readings with Ophtha Top topography were flatter than with the IOL-Master and Lenstar devices, while the Pearson correlation coefficients were over 0.97. The J0 and J45 with Ophtha Top topography were smaller compared with Lenstar and IOL-Master, while was comparable between Lenstar and IOL-Master. CONCLUSION: Ophtha Top topography shows excellent repeatability for measuring corneal parameters. However, differences between the Ophtha TOP topography and Lenstar, IOL-Master both in cornea curvature and the astigmatism should be noted clinically.

14.
Int J Cancer ; 140(1): 103-108, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27646734

RESUMEN

Intratumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) may account for resistance after a period of targeted therapies because drugs destroy only a portion of tumor cells. The recognition of ITH helps identify high-risk patients to make effective treatment decisions. However, ITH studies are confounded by interpatient heterogeneity in NSCLC and a large amount of passenger mutations. To address these issues, we recruited NSCLC patients carrying TP53 mutations and selected driver mutations within recurrently mutated genes in NSCLC. A total of 12-paired normal-tumor tissues were subjected to whole-genome/whole-exome sequencing. From these, 367 non-silent mutations were selected as driver mutations and deeply sequenced in 61 intratumoral microdissections. We identified a universal prevalence of heterogeneity in all 12 tumors, indicating branched evolution. Although TP53 mutations were observed in single biopsy of all 12 tumors, most tumors consist of both TP53 mutated and non-mutated cells in separate regions within the same tumor. This suggests the late molecular timing of the acquisition of TP53 mutations; therefore, the detection of TP53 mutations in a single biopsy may simply not reflect the early malignant potential. In addition, we identified regions of loss of heterozygosity surrounding TP53 and CDKN2A mutations in tumor 711, which also exhibited heterogeneity in different regional samples. Because the ITH of driver mutations likely has clinical consequences, further efforts are needed to limit the impact of ITH and to improve therapeutic efficiency, which will benefit NSCLC patients receiving targeted treatments.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Mutación , Análisis de Secuencia de ADN/métodos , Proteína p53 Supresora de Tumor/genética , Progresión de la Enfermedad , Evolución Molecular , Heterogeneidad Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Pérdida de Heterocigocidad , Filogenia
16.
Asian Pac J Cancer Prev ; 16(1): 175-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25640347

RESUMEN

Rad51, a key factor in the homologous recombination pathway for the DNA double-strand break repair, plays a vital role in genesis of non-small-cell lung cancer (NSCLC). In recent years, more and more studies indicate that high expression of Rad51 is of great relevance to resistance of NSCLC to chemotherapeutic agents and ionizing radiation. However, the underlying molecular mechanisms are poorly understood. In this study, we investigated the role of single Rad51 on cell viability in vitro. Our results show that depletion of endogenous Rad51 is sufficient to inhibit the growth of the A549 lung cancer cell line, by accumulating cells in G1 phase and inducing cell death. We conclude that independent Rad51 expression is critical to the survival of A549 cells and can be an independent prognostic factor in NSCLC patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Supervivencia Celular/genética , Neoplasias Pulmonares/genética , Recombinasa Rad51/genética , Muerte Celular/genética , Línea Celular Tumoral , Roturas del ADN de Doble Cadena , Reparación del ADN/genética , Fase G1/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos
17.
Hum Mol Genet ; 23(20): 5505-17, 2014 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-24852370

RESUMEN

Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.5-1.0 mU/l, are associated with significant differences in blood pressure, BMI, dyslipidemia, risk of atrial fibrillation and atherosclerosis. Most of the variance in TSH levels is thought to be genetically influenced. We conducted a genome-wide association study of TSH levels in 1346 Chinese Han individuals. In the replication study, we genotyped four candidate SNPs with the top association signals in an independent isolated Chinese She cohort (n = 3235). We identified a novel serum TSH susceptibility locus within XKR4 at 8q12.1 (rs2622590, Pcombined = 2.21 × 10(-10)), and we confirmed two previously reported TSH susceptibility loci near FOXE1 at 9q22.33 and near CAPZB at 1p36.13, respectively. The rs2622590_T allele at XKR4 and the rs925489_C allele near FOXE1 were correlated with low TSH levels and were found to be nominally associated to patients with papillary thyroid carcinoma (PTC) (OR = 1.41, P= 0.014 for rs2622590_T, and OR = 1.61, P= 0.030 for rs925489_C). The rs2622590 and rs925489 genotypes were also correlated with the expression levels of FOXE1 and XKR4, respectively, in PTC tissues (P = 2.41 × 10(-4) and P= 0.02). Our findings suggest that the SNPs in XKR4 and near FOXE1 are involved in the regulation of TSH levels.


Asunto(s)
Carcinoma/genética , Factores de Transcripción Forkhead/genética , Hipotiroidismo/genética , Proteínas de Transporte de Membrana/genética , Neoplasias de la Tiroides/genética , Tirotropina/sangre , Proteínas Reguladoras de la Apoptosis , Pueblo Asiatico/genética , Proteína CapZ/genética , Carcinoma Papilar , China , Cromosomas Humanos Par 8/genética , Cromosomas Humanos Par 9/genética , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Proteínas de la Membrana , Polimorfismo de Nucleótido Simple , Cáncer Papilar Tiroideo , Tirotropina/genética
18.
Hum Genet ; 133(5): 661-71, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24346624

RESUMEN

The BACH2 gene regulates B cell differentiation and function and has been reported to be a shared susceptibility gene for several autoimmune diseases. Our previous genome-wide association study (GWAS) indicated that several single nucleotide polymorphisms (SNPs) in the BACH2 gene are associated with Graves' disease (GD) in the Chinese Han population; however, the association did not achieve genome-wide significance levels. Recently, this association of BACH2 with GD was confirmed in Caucasians in the UK population, but fine mapping in this region has not yet been reported. Here, we provide a refined analysis of a 331-kb region in the BACH2 gene, which harbors 359 SNPs, using GWAS data from 1,442 GD patients and 1,468 controls. The SNPs rs2474619 and rs9344996 were implied as the independent variants associated with GD by forward and two-locus logistic regression analysis. We genotyped eight out of 10 tagSNPs with P < 1 × 10(-3) in 3,508 GD patients and 3,209 controls, the results also showed that rs2474619 was independently associated with GD in the combined population from GWAS and the second stage (P = 1.81 × 10(-5)). The rs2474619 and rs9344996 were further genotyped in the third stage cohorts, and rs2474619 showed evidence of association with GD at genome-wide significance levels in the combined population (P = 3.28 × 10(-8), odds ratio = 1.13). The association of rs9344996 with GD can be explained by its linkage to rs2474619 in the combined population. Our study clearly demonstrated that BACH2 is a susceptibility gene for GD in the Chinese Han population and further supported rs2474619, in intron 2 of BACH2, is the best association signal with GD. However, the mechanism by which BACH2 confers increased risk of GD requires further study.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Etnicidad/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Enfermedad de Graves/genética , Enfermedades Autoinmunes/genética , Secuencia de Bases , China , Cartilla de ADN , Humanos , Modelos Logísticos , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa
19.
Chembiochem ; 14(9): 1094-104, 2013 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-23703900

RESUMEN

Resveratrol (3,5,4'-trihydroxystilbene, RES), a star among dietary polyphenols, shows a wide range of biological activities, but it is rapidly and extensively metabolized into its glucuronide and sulfate conjugates as well as to the corresponding reduced products. This begs the question of whether the metabolites of RES contribute to its in vivo biological activity. To explore this possibility, we synthesized its glucuronidation (3-GR and 4'-GR) and reduction (DHR) metabolites, and evaluated the effect of these structure modifications on biological activities, including binding ability with human serum albumin (HSA), antioxidant activity in homogeneous solutions and heterogeneous media, anti-inflammatory activity, and cytotoxicity against various cancer cell lines. We found that 1) 4'-GR, DHR and RES show nearly equal binding to HSA, mainly through hydrogen bonding, whereas 3-GR adopts a quite different orientation mode upon binding, thereby resulting in reduced ability; 2) 3-GR shows comparable (even equal) ability to RES in FRAP- and AAPH-induced DNA strand breakage assays; DHR, 3-GR, and 4'-GR exhibit anti-hemolysis activity comparable to that of RES; additionally, 3-GR and DHR retain some degree activity of the parent molecule in DPPH.-scavenging and cupric ion-initiated oxidation of LDL assays, respectively; 3) compared to RES, 4'-GR displays equipotent ability in the inhibition of COX-2, and DHR presents comparable activity in inhibiting NO production and growth of SMMC-7721 cells. Relative to RES, its glucuronidation and reduction metabolites showed equal, comparable, or some degree of activity in the above assays, depending on the specific compound and test model, which probably supports their roles in contributing to the in vivo biological activities of the parent molecule.


Asunto(s)
Glucurónidos/química , Estilbenos/metabolismo , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antiinflamatorios/toxicidad , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Sitios de Unión , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Glucurónidos/síntesis química , Hemólisis/efectos de los fármacos , Humanos , Cinética , Ratones , Simulación del Acoplamiento Molecular , Oxidación-Reducción , Unión Proteica , Estructura Terciaria de Proteína , Resveratrol , Albúmina Sérica/química , Albúmina Sérica/metabolismo , Estilbenos/química
20.
Chin Med J (Engl) ; 125(8): 1500-3, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22613659

RESUMEN

BACKGROUND: Numerous studies have shown that time spent on television (TV) viewing is positively associated with obesity. The aim of this study was to examine the potential association between excessive TV viewing and obesity, especially abdominal obesity, among children and adolescents in mainland of China. METHODS: A total of 4708 children and adolescents aged 6 to 16 years were recruited for the study. Anthropometric measures were conducted by trained personnels. A self-report questionnaire was designed to gather information on TV time, physical activity, diet habits, maternal body mass index (BMI), birth weight, and on general demographics, including age and gender, and socio-economic status. RESULTS: The prevalence of obesity in this group was 6.5%. Linear regression analysis indicated that high TV viewing time (≥ 1.5 h/d) was significantly associated with higher BMI, waist circumference (WC), and waist-to-height ratio (WHtR). In addition, the high TV time group had 1.3 times the odds of obesity as compared to the low TV time group. Likewise, high TV viewing time increased the OR value 1.32 and 1.21 times higher in WC- and WHtR-defined obesity. Within the non-obesity group, high TV viewing time was also positively associated with higher WC and WHtR. All these correlations remained significant after adjustment for the confounding variables. CONCLUSIONS: Excessive TV viewing might increase the risk of obesity among Chinese youth. Reducing TV viewing time may be beneficial to improve health outcomes, both in the short- and long term. This finding should be taken into account in future designs of intervention policies to prevent childhood and adolescent obesity in China.


Asunto(s)
Hábitos , Obesidad/epidemiología , Televisión , Adolescente , Índice de Masa Corporal , Niño , China/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Prevalencia , Circunferencia de la Cintura
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