Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 20 de 319
Filtrar
1.
J Am Chem Soc ; 146(14): 10032-10043, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38563705

RESUMEN

The controlled creation, selective exposure, and activation of more basal planes while simultaneously minimizing the generation and exposure of edge sites are crucial for accelerating methanol synthesis from CO2 hydrogenation over MoS2 catalysts but remain a bottleneck. Here, we report a facile method to fabricate heteronanotube catalysts with single-layer MoS2 coaxially encapsulating the carbon nanotubes (CNTs@MoS2) through host-guest chemistry. Inheriting the long tubular structure of CNTs, the grown MoS2 nanotubes exhibit significantly more basal planes than bulk MoS2 crystals. More importantly, the tubular curvature not only promotes strain and sulfur vacancy (Sv) generation but also preferentially exposes more in-plane Sv while limiting edge Sv exposure, which is conducive to methanol synthesis. Both the strain and layer number of MoS2 can be easily and finely adjusted by altering CNT diameter and quantity of precursors. Remarkably, CNTs@MoS2 with monolayer MoS2 and maximum strain displayed methanol selectivity of 78.1% and methanol space time yield of 1.6 g gMoS2-1 h-1 at 260 °C and GHSV of 24000 mL gcat.-1 h-1, representing the best results to date among Mo-based catalysts. This study provides prospects for novel catalyst design by synthesizing coaxial tubular heterostructure to create additional catalytic sites and ultimately enhance conversion and selectivity.

2.
BMC Plant Biol ; 24(1): 274, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605295

RESUMEN

Temperature is one of the important environmental factors affecting plant growth, yield and quality. Moreover, appropriately low temperature is also beneficial for tuber coloration. The red potato variety Jianchuanhong, whose tuber color is susceptible to temperature, and the purple potato variety Huaxinyangyu, whose tuber color is stable, were used as experimental materials and subjected to 20 °C (control check), 15 °C and 10 °C treatments during the whole growth period. The effects of temperature treatment on the phenotype, the expression levels of structural genes related to anthocyanins and the correlations of each indicator were analyzed. The results showed that treatment at 10 °C significantly inhibited the potato plant height, and the chlorophyll content and photosynthetic parameters in the leaves were reduced, and the enzyme activities of SOD and POD were significantly increased, all indicating that the leaves were damaged. Treatment at 10 °C also affected the tuberization of Huaxinyangyu and reduced the tuberization and coloring of Jianchuanhong, while treatment at 15 °C significantly increased the stem diameter, root-to-shoot ratio, yield and content of secondary metabolites, especially anthocyanins. Similarly, the expression of structural genes were enhanced in two pigmented potatoes under low-temperature treatment conditions. In short, proper low temperature can not only increase yield but also enhance secondary metabolites production. Previous studies have not focused on the effects of appropriate low-temperature treatment during the whole growth period of potato on the changes in metabolites during tuber growth and development, these results can provide a theoretical basis and technical guidance for the selection of pigmented potatoes with better nutritional quality planting environment and the formulation of cultivation measures.


Asunto(s)
Solanum tuberosum , Temperatura , Solanum tuberosum/metabolismo , Antocianinas/metabolismo , Frío , Fotosíntesis , Tubérculos de la Planta/genética
3.
BMC Cancer ; 24(1): 1227, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39369189

RESUMEN

BACKGROUND: In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population. METHODS: This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS. RESULTS: A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 - 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44-13.61), 7.5 months (95% CI 7.33-8.17), and 4.01 months (95% CI 3.94-4.08), respectively, with a log-rank test p-value < 0.001. CONCLUSION: This study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.


Asunto(s)
Cetuximab , Neoplasias de Cabeza y Cuello , Recurrencia Local de Neoplasia , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Cetuximab/uso terapéutico , Cetuximab/administración & dosificación , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Anciano , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Medición de Riesgo/métodos , Taiwán/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Adulto , Factores de Riesgo
4.
BMC Cancer ; 24(1): 1320, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39456017

RESUMEN

BACKGROUND: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. METHODS: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. RESULTS: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578). CONCLUSIONS: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.


Asunto(s)
Quimioradioterapia Adyuvante , Neoplasias de la Boca , Humanos , Masculino , Femenino , Neoplasias de la Boca/terapia , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Taiwán/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Anciano , Quimioradioterapia Adyuvante/métodos , Dosificación Radioterapéutica , Adulto , Extensión Extranodal , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad
5.
J Cell Mol Med ; 27(17): 2594-2602, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37581476

RESUMEN

Head and neck squamous cell carcinomas (HNSCCs) are generally associated with tobacco consumption, alcohol abuse or both. Mucins (MUCs) are high-molecular-weight glycoproteins produced by many epithelial tissues. Many studies have indicated that MUCs play an important role in cancer metastasis. MUC6 expression has been observed in gastric and oncocytic phenotypes and plays an important role during cancer progression. We found that levels of MUC6 are lower in Asian HNCC patients and affect the disease-free survival of HNCC patients. Next, we investigated the combined effect of MUC6 polymorphisms and exposure to environmental carcinogens on the susceptibility to and clinicopathological characteristics of HNCC. Three single-nucleotide polymorphisms (SNPs) of MUC6 (rs7481521, rs6597947 and rs61869016) were analysed using real-time PCR. After adjusting for other co-variants, we found that carrying a CC genotype at MUC6 rs6597947 led to a lower risk of developing oral squamous cell carcinoma (OSCC) than wild-type carriers among non-betel-quid chewers. Moreover, male oral cancer patients who carried the AA + CC genotype at MUC6 rs6597947 had a lower risk of lymph node metastasis than other genotypes, suggesting a significant functional compromise and decompensated disease. Therefore, our findings suggest that genetic variations in MUC6 may correlate to OSCC and indicate the progression in OSCC patients.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Masculino , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Polimorfismo de Nucleótido Simple/genética , Genotipo , Predisposición Genética a la Enfermedad , Estudios de Casos y Controles , Factores de Riesgo , Mucina 6/genética
6.
Biochem Biophys Res Commun ; 629: 183-188, 2022 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-36152451

RESUMEN

Ketamine is a commonly used dissociative anesthetic in clinical applications. However, the abuse potential has posted limits to its use and the mechanism remains to be studied. We aimed to investigate the changes of dopamine D1 receptors (D1R), phosphorylation of extracellular-regulated protein kinase 1/2 (p-ERK1/2), and c-Fos expression in the nucleus accumbens (NAc) of ketamine abuse rats. Ketamine induced severe anxiety in rats, as shown by an open field test. Nissl staining demonstrated clearly different morphologies between neurons of ketamine abuse rats and normal rats. The molecular expression changes were examined using immunohistochemistry assay and western blotting. D1R, p-ERK1/2, and c-Fos were significantly highly-expressed in NAc during ketamine exposure and were decreased by D1R antagonist SCH23390 and MAPK kinases inhibitor U0126. Taken together, the results suggest that ketamine abuse may induce the overexpression of c-Fos in NAc by up-regulating the expression of D1R and p-ERK1/2.


Asunto(s)
Ketamina , Núcleo Accumbens , Anestésicos Disociativos/farmacología , Animales , Ketamina/farmacología , Sistema de Señalización de MAP Quinasas/fisiología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Núcleo Accumbens/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Receptores de Dopamina D1/metabolismo , Transducción de Señal
7.
BMC Cancer ; 22(1): 296, 2022 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-35313837

RESUMEN

BACKGROUND: The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan. METHODS: Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records. RESULTS: In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999-2002), 30% (2003-2006), 30% (2007-2010), 29% (2011-2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999-2002), 1.06 (2003-2006), 1.52 (2007-2010) to 1.74 (2011-2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35-0.76), p = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p < 0.01). CONCLUSION: The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.


Asunto(s)
Areca/efectos adversos , Neoplasias Orofaríngeas/epidemiología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/complicaciones , Femenino , Genotipo , Conductas de Riesgo para la Salud , Papillomavirus Humano 16/genética , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Masticación , Neoplasias Orofaríngeas/mortalidad , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Taiwán/epidemiología
8.
PLoS Comput Biol ; 17(10): e1008802, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34653176

RESUMEN

Texture regularity, such as the repeating pattern in a carpet, brickwork or tree bark, is a ubiquitous feature of the visual world. The perception of regularity has generally been studied using multi-element textures in which the degree of regularity has been manipulated by adding random jitter to the elements' positions. Here we used three-factor Maximum Likelihood Conjoint Measurement (MLCM) for the first time to investigate the encoding of regularity information under more complex conditions in which element spacing and size, in addition to positional jitter, were manipulated. Human observers were presented with large numbers of pairs of multi-element stimuli with varying levels of the three factors, and indicated on each trial which stimulus appeared more regular. All three factors contributed to regularity perception. Jitter, as expected, strongly affected regularity perception. This effect of jitter on regularity perception is strongest at small element spacing and large texture element size, suggesting that the visual system utilizes the edge-to-edge distance between elements as the basis for regularity judgments. We then examined how the responses of a bank of Gabor wavelet spatial filters might account for our results. Our analysis indicates that the peakedness of the spatial frequency (SF) distribution, a previously favored proposal, is insufficient for regularity encoding since it varied more with element spacing and size than with jitter. Instead, our results support the idea that the visual system may extract texture regularity information from the moments of the SF-distribution across orientation. In our best-performing model, the variance of SF-distribution skew across orientations can explain 70% of the variance of estimated texture regularity from our data, suggesting that it could provide a candidate read-out for perceived regularity.


Asunto(s)
Modelos Neurológicos , Reconocimiento Visual de Modelos/fisiología , Algoritmos , Biología Computacional , Humanos , Psicofísica , Propiedades de Superficie , Análisis de Ondículas
9.
Int J Med Sci ; 19(6): 1023-1028, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35813302

RESUMEN

Triple-negative breast cancer (TNBC) is the third most common female cancer in Taiwan. EZH2 plays an important role in cancer development through transcriptional repression by chromatin remodeling. However, the expression of EZH2 in breast cancer is highly correlated with tumorigenesis, and patient survival is not matched to TNBC. Furthermore, it has not been determined if specific EZH2 genetic variants are associated with breast cancer risk. In this paper, we evaluated the survival of different types of breast cancer. The results indicated that a lower expression of EZH2 led to poor survival of TNBC patients. Therefore, we aimed at studying the relationship between genetic polymorphisms of EZH2 and susceptibility to TNBC in Taiwan. Four single-nucleotide polymorphisms (SNPs) of EZH2 (rs6950683, rs2302427, rs3757441, and rs41277434) were analyzed by real-time PCR genotyping in 176 patients with TNBC and 1000 cancer-free controls. The results showed that TNBC patients under 60 years old who carried a TC or CC genotype at EZH2 rs6950683 and re3757441 had a tumor size of 20 mm or smaller (T1). Thus, this study is the first to examine the age and mutant genes associated with EZH2 SNPs in TNBC progression and development in Taiwan.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Proteína Potenciadora del Homólogo Zeste 2/genética , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Taiwán/epidemiología , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología
10.
J Sci Food Agric ; 102(9): 3887-3896, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34952968

RESUMEN

BACKGROUND: Quercetin (Que) has many pharmacological activities, such as anticancer, antioxidant, cardiovascular protection, antihypertensive and lipid-lowering activities. However, its poor water solubility greatly limits its application in medicine and food. γ-Cyclodextrin metal-organic frameworks (γ-CD-MOFs) are novel porous carriers for loading functional products. In this study, Que was successfully loaded into γ-CD-MOFs, and the new compound (Que-CD-MOFs) was characterised by X-ray diffraction, infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy. RESULTS: The apparent solubility of Que-CD-MOFs was enhanced by 100-fold compared with that of pure Que. The free radical scavenging ability of the encapsulated Que was significantly improved. The cytotoxicity of Que-CD-MOFs to HK-2 cells was decreased, and their inhibition on HT-29 tumour cells was maintained, as confirmed by CCK-8 assays. Flow cytometry of HT-29 cells showed that Que-CD-MOFs can inhibit G2 phase cells. Based on molecular modelling, Que molecules were preferentially located inside the cavities of γ-CD pairs in γ-CD-MOFs. CONCLUSION: γ-CD-MOFs are promising carriers for bioactive agents in food and pharmaceutical applications. © 2021 Society of Chemical Industry.


Asunto(s)
Ciclodextrinas , Estructuras Metalorgánicas , Disponibilidad Biológica , Ciclodextrinas/química , Estructuras Metalorgánicas/química , Quercetina/farmacología , Solubilidad , Difracción de Rayos X
11.
Mol Med ; 27(1): 147, 2021 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-34773993

RESUMEN

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.


Asunto(s)
Factores de Crecimiento de Fibroblastos , Hipertensión Renal , Nefritis , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Línea Celular , Acetato de Desoxicorticosterona , Factores de Crecimiento de Fibroblastos/sangre , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/uso terapéutico , Humanos , Hipertensión Renal/inducido químicamente , Hipertensión Renal/tratamiento farmacológico , Hipertensión Renal/metabolismo , Hipertensión Renal/patología , Interleucina-6/metabolismo , Riñón/metabolismo , Riñón/patología , Masculino , Ratones Endogámicos C57BL , Nefritis/inducido químicamente , Nefritis/tratamiento farmacológico , Nefritis/metabolismo , Nefritis/patología , Estrés Oxidativo , Proteínas Recombinantes/uso terapéutico , Cloruro de Sodio Dietético , Factor de Necrosis Tumoral alfa/metabolismo
12.
J Enzyme Inhib Med Chem ; 36(1): 1715-1731, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34425716

RESUMEN

Hippo signalling pathway plays a crucial role in tumorigenesis and cancer progression. In this work, we identified an N-aryl sulphonamide-quinazoline derivative, compound 9i as an anti-gastric cancer agent, which exhibited potent antiproliferative ability with IC50 values of 0.36 µM (MGC-803 cells), 0.70 µM (HCT-116 cells), 1.04 µM (PC-3 cells), and 0.81 µM (MCF-7 cells), respectively and inhibited YAP activity by the activation of p-LATS. Compound 9i was effective in suppressing MGC-803 xenograft tumour growth in nude mice without obvious toxicity and significantly down-regulated the expression of YAP in vivo. Compound 9i arrested cells in the G2/M phase, induced intrinsic apoptosis, and inhibited cell colony formation in MGC-803 and SGC-7901 cells. Therefore, compound 9i is to be reported as an anti-gastric cancer agent via activating the Hippo signalling pathway and might help foster a new strategy for the cancer treatment by activating the Hippo signalling pathway regulatory function to inhibit the activity of YAP.


Asunto(s)
Antineoplásicos/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Quinazolinas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Sulfonamidas/farmacología , Animales , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Carcinogénesis/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Regulación de la Expresión Génica/efectos de los fármacos , Vía de Señalización Hippo , Humanos , Ratones Desnudos , Estructura Molecular , Quinazolinas/síntesis química , Transducción de Señal , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
13.
J Am Chem Soc ; 142(32): 13823-13832, 2020 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-32667195

RESUMEN

Despite widespread use of heterogeneous Pd catalysts in Suzuki-Miyaura coupling reactions, detailed roles of Pd, especially the nature of its active species, are still a topic of controversial debate. While some studies showed an active surface of Pd nanoparticles or nanoclusters acting heterogeneously, others claimed soluble Pd species leached from the metallic Pd to be active species which are homogeneous in nature. Besides, within the homogeneous mechanism, how the Pd leaches and promotes the cross-coupling reaction is then another question that needs to be addressed. It could be envisioned that if the soluble Pd species and solid-phase Pd are physically separated, the mechanism of Suzuki-Miyaura coupling could then be confirmed through examining the catalytic activity in different reaction regions. Herein we use microporous Stöber silica as a membrane to separate the soluble Pd species from solid Pd and conduct size-selective reactions which allow the passage of leaching Pd species, but not of reactants or products larger than the membrane aperture. With this strategy, we have been able to differentiate the surface reaction from the solution cross-coupling. We find that the leached Pd species are the only genuine catalytic intermediate in the cross-coupling reactions. We also confirm that oxidative addition of aryl halides to the solid Pd leads to leaching of the soluble Pd species which is necessary to promote Suzuki-Miyaura reactions.

14.
Am J Pathol ; 189(1): 190-199, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30315765

RESUMEN

Oral squamous cell carcinoma (OSCC) is the most common malignant cancer, with high mortality rates in advanced stages. Recent studies have shown that the expression of ALPK1 mRNA and its inhibitory differentiation function are associated with cancer progression. However, the expression and clinicopathologic features of ALPK1 in OSCC remain unexplored. Herein, the authors investigated the expression patterns of ALPK1 in 39 matched OSCC patients and examined the relationship between ALPK1 protein expression and clinicopathologic factors using immunohistochemical scores. Using Western blot analysis, ALPK1 expression was found to be significantly higher in tumor tissues than that in nontumor tissues. Through an immunoreactive scoring system, a significantly higher number of advanced-stage tumor size T4 and lymph node metastasis N2 exhibited higher ALPK1 expression levels than that exhibited by T1/T2/T3 tumors and N0/N1. In addition, ALPK1 protein expression was aberrant in malignant oral cancer cell lines compared with that in pre-malignant oral epithelial cells, whereas minimal expression was observed in normal oral epithelial cells. Knockdown of ALPK1 resulted in a significant reduction in cell growth, migration, and invasion capacity in vitro. Consequently, expression of N-cadherin and vimentin decreased in ALPK1-deficient cells. Thus, these results suggest that ALPK1 serves as a potential biomarker and target for OSCC development in late stages.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Escamosas/enzimología , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/biosíntesis , Proteínas Quinasas/biosíntesis , Neoplasias de la Lengua/enzimología , Adulto , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos CD/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Cadherinas/genética , Cadherinas/inmunología , Cadherinas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Queratinocitos/inmunología , Queratinocitos/metabolismo , Queratinocitos/patología , Metástasis Linfática/genética , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/inmunología , Estadificación de Neoplasias , Proteínas Quinasas/genética , Proteínas Quinasas/inmunología , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/inmunología , Neoplasias de la Lengua/patología , Vimentina/genética , Vimentina/inmunología , Vimentina/metabolismo
15.
J Med Virol ; 92(11): 2804-2812, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32542750

RESUMEN

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.


Asunto(s)
COVID-19/epidemiología , Heces/virología , SARS-CoV-2/fisiología , Esparcimiento de Virus , Adolescente , Antivirales/uso terapéutico , COVID-19/transmisión , Portador Sano/epidemiología , Portador Sano/virología , Niño , Preescolar , China/epidemiología , Familia , Femenino , Hospitalización , Humanos , Incidencia , Lactante , Masculino , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/patogenicidad
16.
BMC Cancer ; 20(1): 832, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32873270

RESUMEN

BACKGROUND: Phase 3 studies suggest that induction chemotherapy (ICT) of cisplatin and 5-fluorouracil plus docetaxel (TPF) is effective but toxic for patients with squamous-cell carcinoma of the head and neck (SCCHN). Dose-dense chemotherapy may yield favorable outcomes compared with standard-dose chemotherapy, yet the optimal induction regimen remains undefined. We assessed the efficacy and tolerability of biweekly dose-dense TPF ICT in patients with SCCHN. METHODS: In this prospective phase II study, We enrolled patients with stage III/IV (AJCC 7th edition) unresectable squamous cell carcinoma of head and neck cancer. Patients received dose-dense TPF (ddTPF) with cisplatin and docetaxel 50 mg/m2 on day 1, leucovorin 250 mg/m2 on day1, followed by 48-h continuous infusion of 2500 mg/m2 of 5-fluorouracil on day 1 and 2, every 2 weeks for 6 cycles followed by radiotherapy. The primary endpoint was the response rate (RR) after ICT. RESULTS: Fifty-eight patients were enrolled from June 2014 to September 2015. Overall RR after ICT was 89.6% [complete response (CR), 31%; partial response (PR), 58.6%]. Grade 3/4 neutropenia, mucositis, and diarrhea incidences were 25.9, 1.7, and 1.7%, respectively. 94.8% of patients completed all treatment courses of ICT without dose reduction. The 3-year overall survival (OS) was 54.3% (95%CI: 39.7 to 66.8%) and progression-free survival (PFS) was 34.3% (95%CI: 22.0 to 46.9%). Multivariate analysis showed that CR after ICT is an independent prognostic factor for OS and PFS. CONCLUSIONS: Six cycles of ddTPF is an active, well-tolerated induction regimen for patients with SCCHN. The presence of CR after ICT predicted long-term survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04397341 , May 21, 2020, retrospectively registered.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Fluorouracilo/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Quimioterapia de Inducción/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Terapia Combinada , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia
17.
J Clin Lab Anal ; 34(3): e23078, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31907994

RESUMEN

BACKGROUND: Different from the diagnosis of bacterial infections, Mycoplasma pneumoniae pneumonia (MPP) is still lacking of convenient non-specific laboratory parameters. METHOD: A total of 125 children with MPP were included in the MPP group and 89 children with Mycoplasma-negative pneumonia were included in the control group, and the sera were collected from the children at both the acute and recovery stages in the two groups. RESULTS: The sialic acid and C3 in the MPP group were significantly higher than those in the control group both at the acute and at the recovery stage. On the other hand, the sialic acid and C3 at the acute stage were significantly higher than those at the recovery stage in the MPP group. However, in the control group, the sialic acid and C3 demonstrated IgG exhibited no significant change between the acute stage and the recovery stage. Lastly, positive correlations between sialic acid level and C3 level were identified in the MPP group at both acute and recovery stages. CONCLUSION: Our study demonstrated that the serum sialic acid correlated with C3 specifically increased in children with MPP, indicating that it might be the important non-specific parameters in the diagnosis of MPP.


Asunto(s)
Complemento C3/metabolismo , Mycoplasma pneumoniae/fisiología , Ácido N-Acetilneuramínico/sangre , Neumonía por Mycoplasma/sangre , Neumonía por Mycoplasma/microbiología , Adolescente , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Complemento C4/metabolismo , Femenino , Humanos , Inmunoglobulina G/sangre , Lactante , Masculino
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(11): 1188-1192, 2020 Nov.
Artículo en Zh | MEDLINE | ID: mdl-33172553

RESUMEN

OBJECTIVE: To investigate the nutritional status of children with cerebral palsy (CP) and the clinical effectiveness of Subjective Global Nutritional Assessment (SGNA) in nutritional assessment of hospitalized children with CP. METHODS: A total of 208 children with CP, aged 1-5 years, who were hospitalized from April to October 2019 were enrolled as subjects. SGNA was used to investigate nutritional status, and the Z-score method recommended by the World Health Organization was used as a reference standard to validate the clinical effectiveness of SGNA. RESULTS: The detection rate of malnutrition in children with CP was 42.3% by SGNA and 39.4% by the Z-score method (P>0.05). The application of SGNA showed high consistency between different evaluators (κ=0.621, P<0.001). With the Z-score method as the reference standard, SGNA had a sensitivity of 80.5%, a specificity of 82.5%, a positive predictive value of 75.0%, and a negative predictive value of 86.7%, and high consistency was observed between the two evaluation methods (κ=0.622, P<0.001). SGNA was moderately consistent with weight-for-age Z-score and height-for-age Z-score (κ=0.495 and 0.478 respectively, P<0.001) and was poorly consistent with weight-for-height Z-score (κ=0.197, P<0.05). CONCLUSIONS: There is a relatively high incidence rate of malnutrition in children with CP. SGNA can be used as a tool to assess the nutritional status of children with CP.


Asunto(s)
Parálisis Cerebral , Niño , Niño Hospitalizado , Preescolar , Humanos , Lactante , Desnutrición , Evaluación Nutricional , Estado Nutricional , Resultado del Tratamiento
19.
Pharmacology ; 103(3-4): 143-150, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30673679

RESUMEN

BACKGROUND: Ganoderma lucidum Polysaccharides (GLPS) were found to possess various pharmacological properties including anti-inflammatory and hepatoprotective activities. However, the effect and possible mechanism of GLPS treatment on liver injury have not yet been reported. Therefore, this study aimed to explore the potential anti-inflammatory and hepatoprotective effects and possible mechanism of GLPS in carbon tetrachloride (CCl4)-induced acute liver injury mice. SUMMARY: GLPS significantly reduced the activation of NLRP3 inflammasome and improved liver function in liver injury mice. It significantly inhibited CCl4-induced changes of alanine aminotransferase and aspartate aminotransferase activities in serum, as well as nitric oxide synthase (NOS) and cytochrome P450 2E1 (CYP2E1) activities in liver tissue; it also remarkably decreased levels of liver weight and index, total bilirubin, interleukin (IL)-1ß, IL-18, IL-6 and tumor necrosis factor-α in serum, as well as malondialdehyde and IL-1ß in liver tissue. Protein expression levels of liver NLRP3, ASC, and Caspase-1 were also downregulated, while the glutathione level in liver tissue was remarkably enhanced in GLPS groups compared to that of the model group. Key Message: These results suggested that GLPS may be a potential for the prevention and treatment of acute liver injury with liver inflammation. The possible mechanism may be related to the inhibition of free radical lipid peroxidation, NOS, and CYP2E1 activities and activation of liver inflammatory factors.


Asunto(s)
Antiinflamatorios/farmacología , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Hígado/efectos de los fármacos , Polisacáridos/farmacología , Reishi , Animales , Antiinflamatorios/aislamiento & purificación , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocromo P-450 CYP2E1/metabolismo , Citocinas/metabolismo , Citoprotección , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Mediadores de Inflamación/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Óxido Nítrico Sintasa/metabolismo , Polisacáridos/aislamiento & purificación , Reishi/química
20.
BMC Pediatr ; 19(1): 181, 2019 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-31167650

RESUMEN

BACKGROUND: Invasive S. pyogenes diseases are uncommon, serious infections with high case fatality rates (CFR). There are few publications on this subject in the field of pediatrics. This study aimed at characterizing clinical and laboratory aspects of this disease in Chinese children. PATIENTS AND METHODS: A retrospective study was conducted and pediatric in-patients with S. pyogenes infection identified by cultures from normally sterile sites were included, who were diagnosed and treated in 9 tertiary hospitals during 2010-2017. RESULTS: A total of 66 cases were identified, in which 37 (56.1%) were male. The median age of these patients, including 11 neonates, was 3.0 y. Fifty-nine (89.4%) isolates were determined from blood. Fever was the major symptom (60/66, 90.9%) and sepsis was the most frequent presentation (64/66, 97.0%, including 42.4% with skin or soft tissue infections and 25.8% with pneumonia. The mean duration of the chief complaint was (3.8 ± 3.2) d. Only 18 (27.3%) patients had been given antibiotics prior to the hospitalization. Among all patients, 15 (22.7%) developed streptococcal toxin shock syndrome (STSS). No S. pyogenes strain was resistant to penicillin, ceftriaxone, or vancomycin, while 88.9% (56/63) and 81.4% (48/59) of the tested isolates were resistant to clindamycin and erythromycin respectively. Most of the patients were treated with ß-lactams antibiotics and 36.4% had been treated with meropenem or imipenem. Thirteen (19.7%) cases died from infection, in which 9 (13.6%) had complication with STSS. CONCLUSIONS: Invasive S. pyogenes infections often developed from skin or soft tissue infection and STSS was the main cause of death in Chinese children. Ongoing surveillance is required to gain a greater understanding of this disease.


Asunto(s)
Infecciones Estreptocócicas/diagnóstico , Streptococcus pyogenes/aislamiento & purificación , Ceftriaxona/uso terapéutico , Preescolar , China , Clindamicina/uso terapéutico , Farmacorresistencia Bacteriana , Eritromicina/uso terapéutico , Femenino , Fiebre/microbiología , Humanos , Lactante , Recién Nacido , Masculino , Penicilinas/uso terapéutico , Neumonía Neumocócica/microbiología , Estudios Retrospectivos , Sepsis/microbiología , Choque Séptico/microbiología , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones de los Tejidos Blandos/microbiología , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes/efectos de los fármacos , Centros de Atención Terciaria/estadística & datos numéricos , Vancomicina/uso terapéutico
SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda