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1.
Clin Genet ; 105(4): 397-405, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38173219

RESUMEN

CCDC88C gene, which encodes coiled-coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole-exome sequencing (trio-based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult-onset epilepsy, whereas patients with biallelic variants displayed infant-onset epilepsy. They all responded well to anti-seizure medications and were seizure-free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non-classical splicing and a variant located at crucial domain, suggesting a sub-molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy-associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus-associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.


Asunto(s)
Epilepsias Parciales , Epilepsia , Hidrocefalia , Lactante , Adulto , Humanos , Epilepsias Parciales/genética , Epilepsia/genética , Hidrocefalia/genética , Genotipo , Estudios de Asociación Genética , Proteínas de Microfilamentos/genética , Péptidos y Proteínas de Señalización Intracelular/genética
2.
Acta Pharmacol Sin ; 45(5): 1002-1018, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38225395

RESUMEN

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Diabetes Mellitus Experimental , Proteína Forkhead Box O3 , Ratones Endogámicos C57BL , Fibrosis Pulmonar , Sirtuina 3 , Xantonas , Animales , Xantonas/farmacología , Xantonas/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Sirtuina 3/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Proteína Forkhead Box O3/metabolismo , Masculino , Humanos , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Estreptozocina , Transducción de Señal/efectos de los fármacos , Transición Endotelial-Mesenquimatosa
3.
Molecules ; 28(14)2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37513401

RESUMEN

An unprecedented N-alkylation of 3-nitroindoles with para-quinone methides was developed for the first time. Using potassium carbonate as the base, a wide range of structurally diverse N-diarylmethylindole derivatives were obtained with moderated to good yields via the protection group migration/aza-1,6-Michael addition sequences. The reaction process was also demonstrated by control experiments. Different from the previous advances where 3-nitrodoles served as electrophiles trapping by various nucleophiles, the reaction herein is featured that 3-nitrodoles is defined with latent N-centered nucleophiles to react with ortho-hydrophenyl p-QMs for construction of various N-diarylmethylindoles.

4.
Cancer Control ; 29: 10732748211053150, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34989251

RESUMEN

BACKGROUND: Breast cancer (BC), especially metastatic BC, is one of the most lethal diseases in women. CA 125 and CA 15-3 are commonly used indicators for diagnosis and prognosis of BC. Some serological indicators, such as lactate dehydrogenase (LDH) and C-reactive protein (CRP), can also be used to assess the prognosis and progression in BC. METHODS: Univariate Cox regression analysis and LASSO regression analysis were performed to identify prognostic factors and build prognostic models. We distributed the patients into 2 groups based on the median risk score, analyzed prognosis by Kaplan-Meier curve, and screened independent prognostic factors by multivariate Cox regression analysis. RESULT: We identified 4 indicators-LDH, CRP, CA 15-3, and CA 125-related to the prognosis in BC and established a prognostic model. The high LDH group showed worse overall survival (OS) than low LDH group (P = .017; hazard ratio (HR), 1.528; 95% confidence interval (CI), 1.055-2.215). The high CRP group showed worse OS than low CRP group (P = .004; HR, 1.666; 95% CI, 1.143-2.429). The high CA153 group showed worse OS than low CA 15-3 group (P=.011; HR, 1.563; 95% CI, 1.075-2.274). The high CA 125 group showed worse OS than low CA 125 group (P = .021; HR, 1.499; 95% CI, 1.031-2.181). The area under the curve for risk score was .824, Ki-67 was .628, age was .511, and grade was .545. Risk score was found to be an independent prognostic factor using multivariate Cox regression analysis. CONCLUSION: We successfully established an optimization model by combining 4 prognosis-related indicators to assess the prognosis in patients with metastatic BC.


Asunto(s)
Antígenos de Neoplasias/sangre , Neoplasias de la Mama/sangre , Proteína C-Reactiva/análisis , Antígeno Ca-125/sangre , L-Lactato Deshidrogenasa/sangre , Adulto , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo
5.
Neoplasma ; 69(4): 965-975, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35723196

RESUMEN

NPM1 plays an important role in the occurrence and development of leukemia and various solid tumors. This study aimed to investigate the expression of NPM1 in gastric cancer (GC) and adjacent normal tissues, study the relationship between NPM1 expression and clinicopathological characteristics in GC patients, and explore the impact of NPM1 expression on the diagnosis and prognosis of GC. We used tissue microarray immunohistochemical analysis to examine the expression level of NPM1 in GC and adjacent tissues and analyzed the relationship between NPM1 expression, clinicopathological factors, and GC prognosis. Prognostic values of NPM1 mRNA were also investigated using an online database. qRT-PCR was used to detect the expression of NPM1 mRNA in cancer and adjacent tissues. According to microarray immunohistochemical analysis and qRT-PCR results, NPM1 had a high expression in all adjacent normal tissues. Microarray immunohistochemical analyses demonstrated that the NPM1 was lowly expressed in 75.5% of GC tissues but highly expressed in 24.5% of GC tissues. qRT-PCR results showed NPM1 mRNA low expression in most GC tissues. NPM1 high expression group was associated with a better overall survival rate and disease-free survival rate than the NPM1 low expression group (p<0.01). This result is consistent with that of the online database. The receiver operating characteristics curve showed that NPM1 was valuable in the diagnosis of GC. The assessment of NPM1 expression in GC samples may represent a useful tool for GC diagnosis and prognosis assessment.


Asunto(s)
Neoplasias Gástricas , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleofosmina , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
6.
Chemphyschem ; 22(15): 1645-1654, 2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34050588

RESUMEN

Adsorption of N2 on Mo6 S8 q _Vx clusters (x=0, 1, 2; q=0, ±1) were systematically studied by density functional theory calculations with dispersion corrections. It was found that the N2 can be chemisorbed and undergo non-dissociative activation on single or double metal atoms. The adsorption and activation are influenced by metal types (V or Mo), N2 coordination modes and charge states of the clusters. Particularly, anionic Mo6 S8 - _V2 clusters have remarkable ability to fix and activate N2 . In Mo6 S8 - _V2 , two V atoms prefer to adsorb on two adjacent S-Mo-S hollow sites, leading to the formation of a supported V…V unit. The N2 is bridged side-on coordinated with these two V atoms with high adsorption energy and significant charge transfer. The bond order, bond length and vibration frequency of the adsorbed N2 are close to those of a N-N single bond.

7.
Phys Chem Chem Phys ; 23(1): 347-355, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33346760

RESUMEN

Structures of non-stoichiometric MoxSy clusters (x = 2-4; y = 2-10) were studied by density functional calculations with global optimization. Besides 1T phase like structures, a novel regular grid structure in which Mo atoms are well separated by S atoms was found, which might be used as a building-block to construct a new type of two-dimensional molybdenum sulfide monolayer. The hydrogen molecule prefers to be adsorbed onto Mo atoms rather than S atoms, and Mo atoms with less S coordination have a higher ability to adsorb H2. In addition, the reaction pathways for H2 dissociation were studied on two clusters with the highest H2 adsorption energy (Mo2S4 and Mo3S3). The vacant bridge site of Mo-Mo in S-deficient clusters, which corresponds to the sulfur vacancy in the bulk phase MoS2, is favored by H atom adsorption and plays an important role in the H atom transfer on MoxSy clusters. Our results provide a new aspect to understand the reason why S defect in MoS2 and MoS2 with an Mo-edge could enhance the catalytic performance in the hydrogen evolution reaction.

8.
Acta Pharmacol Sin ; 42(1): 18-26, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32144337

RESUMEN

The first description of the medical use of licorice appeared in "Shennong Bencao Jing", one of the well-known Chinese herbal medicine classic books dated back to 220-280 AD. As one of the most commonly prescribed Chinese herbal medicine, licorice is known as "Guo Lao", meaning "a national treasure" in China. Modern pharmacological investigations have confirmed that licorice possesses a number of biological activities, such as antioxidation, anti-inflammatory, antiviral, immune regulation, and liver protection. 18ß-glycyrrhetinic acid is one of the most extensively studied active integrants of licorice. Here, we provide an overview of the protective effects of 18ß-glycyrrhetinic acid against various acute and chronic liver diseases observed in experimental models, and summarize its pharmacological effects and potential toxic/side effects at higher doses. We also make additional comments on the important areas that may warrant further research to support appropriate clinical applications of 18ß-glycyrrhetinic acid and avoid potential risks.


Asunto(s)
Ácido Glicirretínico/análogos & derivados , Hepatopatías/prevención & control , Sustancias Protectoras/uso terapéutico , Animales , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/uso terapéutico , Ácido Glicirretínico/toxicidad , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hepatopatías/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/toxicidad
9.
Eur Heart J ; 41(46): 4415-4422, 2020 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-33211823

RESUMEN

AIMS: The aim of this study was to clarify the effect of ß-blockers (BBs) on respiratory function and survival in patients with chronic obstructive pulmonary disease with cardiovascular disease (CVD), as well as the difference between the effects of cardioselective and noncardioselective BBs. METHODS AND RESULTS: We searched for relevant literature in four electronic databases, namely, PubMed, EMBASE, Cochrane Library, and Web of Science, and compared the differences in various survival indicators between patients with chronic obstructive pulmonary disease taking BBs and those not taking BBs. Forty-nine studies were included, with a total sample size of 670 594. Among these, 12 studies were randomized controlled trials (RCTs; seven crossover and five parallel RCTs) and 37 studies were observational (including four post hoc analyses of data from RCTs). The hazard ratios (HRs) of chronic obstructive pulmonary disease exacerbation between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.77 [95% confidence interval (CI) 0.67, 0.89], 0.72 [95% CI 0.56, 0.94], and 0.98 [95% CI 0.71, 1.34, respectively] (HRs <1 indicate favouring BB therapy). The HRs of all-cause mortality between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.70 [95% CI 0.59, 0.83], 0.60 [95% CI 0.48, 0.76], and 0.74 [95% CI 0.60, 0.90], respectively (HRs <1 indicate favouring BB therapy). Patients with Chronic obstructive pulmonary disease treated with cardioselective BBs showed no difference in ventilation effect after the use of an agonist, in comparison with placebo. The difference in mean change in forced expiratory volume in 1 s was 0.06 [95% CI -0.02, 0.14]. CONCLUSION: The use of BBs in patients with chronic obstructive pulmonary disease is not only safe but also reduces their all-cause and in-hospital mortality. Cardioselective BBs may even reduce chronic obstructive pulmonary disease exacerbations. In addition, cardioselective BBs do not affect the action of bronchodilators. Importantly, BBs reduce the heart rate acceleration caused by bronchodilators. BBs should be prescribed freely when indicated in patients with chronic obstructive pulmonary disease and heart disease.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedad Pulmonar Obstructiva Crónica , Antagonistas Adrenérgicos beta/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Volumen Espiratorio Forzado , Humanos , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico
10.
Int J Syst Evol Microbiol ; 70(7): 4250-4260, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32568031

RESUMEN

Two yellow-pigmented, Gram-stain-negative, aerobic, rod-shaped bacteria were isolated from the water of the hypersaline Chaka Salt Lake (strain SaA2.12T) and sediment of Qinghai Lake (strain LaA7.5T), PR China. According to the 16S rRNA phylogeny, the isolates belong to the genus Flavobacterium, showing the highest 16S rRNA sequence similarities to Flavobacterium arcticum SM1502T(97.6-97.7 %) and Flavobacterium suzhouense XIN-1T(96.5-96.6 %). Moreover, strains SaA2.12T and LaA7.5T showed 99.73 % 16S rRNA sequence similarity to each other. Major fatty acids, respiratory quinones and polar lipids detected in these isolates were iso-C15 : 0, menaquinone-6 and phosphatidylethanolamine, respectively. Strains SaA2.12T and LaA7.5T showed significant unique characteristics between them as well as between the closest phylogenetic members. The highest digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between SaA2.12T and its closest neighbours were 25.3 and 82.8 %, respectively; whereas these values (highest) between LaA7.5T and its closest members were 25.2 and 82.8 %, respectively. The dDDH and ANI values between strains SaA2.12T and LaA7.5T were calculated as 75.9 and 97.2 %, respectively. Therefore, based on polyphasic data, we propose that strain SaA2.12T represents a novel species with the name Flavobacterium salilacus sp. nov., with the type strain SaA2.12T (=KCTC 72220T=MCCC 1K03618T) and strain LaA7.5T as a subspecies within novel Flavobacterium salilacus with the name Flavobacterium salilacus subsp. altitudinum subsp. nov., with the type strain LaA7.5T (=KCTC 72806T=MCCC 1K04372T). These propositions automatically create Flavobacterium salilacus subsp. salilacus subsp. nov. with SaA2.12T (=KCTC 72220T=MCCC 1K03618T) as the type strain.


Asunto(s)
Flavobacterium/clasificación , Lagos/microbiología , Filogenia , Aguas Salinas , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Flavobacterium/aislamiento & purificación , Hibridación de Ácido Nucleico , Fosfatidiletanolaminas/química , Pigmentación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
11.
Future Oncol ; 16(10): 573-584, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32141309

RESUMEN

Aim: To establish and validate a nomogram for the estimation of overall survival of patients with uterine leiomyosarcoma (uLMS). Methods: Information on patients diagnosed as uLMS was retrospectively retrieved from the Surveillance, Epidemiology, and End Results database. The patients were randomly assigned into the training and the validation cohorts. Univariate and multivariate analyses were used to determine the independent prognostic factors for building a nomogram for predicting overall survival. The predictive accuracy was evaluated based on the concordance indices and the calibration plots. Results: A nomogram that combined age, marital status, tumor size, Surveillance, Epidemiology, and End Result stage, surgery and radiation was established. The internal and external concordance indices were 0.748 and 0.745, respectively. The calibration plots approached 45 degrees. Conclusion: The nomogram might be an effective tool for predicting the survival of patients with uLMS.


Asunto(s)
Leiomiosarcoma/mortalidad , Nomogramas , Neoplasias Uterinas/mortalidad , Femenino , Humanos , Leiomiosarcoma/patología , Leiomiosarcoma/cirugía , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Estudios Retrospectivos , Programa de VERF , Tasa de Supervivencia , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía
12.
Curr Microbiol ; 77(10): 2925-2932, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32661679

RESUMEN

A novel bacterium designated SSM4.2T was isolated from seaweed of Gouqi Island, which is the center of the Zhoushan fishing ground in the East China Sea. Strain SSM4.2T was Gram-stain-negative, bright yellow-pigmented, short rod-shaped, non-flagellated, non-spore forming, aerobic and motile by gliding. Growth was observed at 4-37 °C (optimum 25-30 °C), pH 6.0-8.0 (optimum pH 7.0) and 0-2.0% (w/v) NaCl (optimum 0%) concentration. The strain was catalase- and oxidase-positive. Menaquinone-6 (MK-6) was found as the sole respiratory quinone and zeaxanthin as the main carotenoid pigment. The predominant fatty acids (≥ 10%) were iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH and summed feature 3 (C16:1 ω7c /C16:1 ω6c). The major polar lipid was phosphatidylethanolamine (PE). The genome size was 5.7 Mbp. The DNA G + C content was 34.1 mol%. 16S rRNA gene sequence revealed that strain SSM4.2T belongs to the genus Flavobacterium and shares high-sequence similarity with F. limi KACC 18851T (98.1%), F. hydrophilum KACC 19591T (97.6%), F. defluvii KCTC 12612T (97.1%), F. cheongpyeongense KACC 19592T (97.0%) and F. fluviatile KCTC 52446T (96.9%). Strain SSM4.2T had 73.2-84.6% average nucleotide identity and 19.1-29.4% digital DNA-DNA hybridization values with its closest type strains. Based on its phenotypic, chemotaxonomic, phylogenetic and genomic features, strain SSM4.2T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium ajazii sp. nov. is proposed. The type strain is SSM4.2T (= KCTC 72807T = MCCC 1K04370T).


Asunto(s)
Flavobacterium , Filogenia , Algas Marinas , China , Ácidos Grasos/análisis , Flavobacterium/clasificación , Flavobacterium/genética , Flavobacterium/aislamiento & purificación , Islas , ARN Ribosómico 16S/genética , Algas Marinas/microbiología , Especificidad de la Especie , Vitamina K 2/análisis
13.
J Surg Res ; 235: 22-33, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30691798

RESUMEN

BACKGROUND: Accumulating evidence indicated that long noncoding RNAs (lncRNAs) have a wide range of biological functions and may play significant roles in tumorigenesis and progression. However, the understanding of its functions and related competitive endogenous RNAs (ceRNAs) networks is much less than that of protein-coding genes, particularly in colon adenocarcinoma. METHODS: We comprehensively analyzed the sequencing data of protein-coding and noncoding RNAs in colon adenocarcinoma patients from The Cancer Genome Atlas (TCGA) database. Next, we constructed colon adenocarcinoma-specific ceRNA network and evaluated the effect of these RNAs on overall survival (OS) for colon adenocarcinoma patients. RESULTS: Totally, 1138 differentially expressed lncRNAs (DElncRNAs), 245 microRNAs (DEmiRNAs), and 2081 mRNAs (DEmRNAs) were identified using a threshold of |log2FoldChange| >2.0 and adjusted P-value < 0.01. Subsequently, a colon adenocarcinoma-specific ceRNA network was successfully established with133 DElncRNAs, 29 DEmiRNAs, and 55 DEmRNAs. Among ceRNA network, seven DElncRNAs (AL590483.1, AP004609.1, ARHGEF26-AS1, HOX transcript antisense RNA (HOTAIR), ITCH-IT1, KCNQ1OT1, and LINC00491), four DEmiRNAs (hsa-mir-143, hsa-mir-183, hsa-mir-216a, and hsa-mir-424), and six DEmRNAs (FJX1, TPM2, ULBP2, PDCD4, PLAU, and SERPINE1) significantly correlated with OS (all P-value < 0.05). Notably, several interactions were highlighted in the ceRNA network, such as "KCNQ1OT1-hsa-mir-183-PDCD4", "KCNQ1OT1-hsa-mir-424-TPM2", "HOTAIR-hsa-mir-143-SERPINE1", and "ARHGEF26-AS1-hsa-mir-143-SERPINE1". CONCLUSIONS: These findings reveal several molecules might be novel important prognostic factors and potential treatment targets for colon adenocarcinoma. In addition, these observations contribute to a more comprehensive understanding of lncRNA-related ceRNA network and provide novel strategies for subsequent functional studies of lncRNAs in colon adenocarcinoma.


Asunto(s)
Adenocarcinoma/genética , Neoplasias del Colon/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Adenocarcinoma/mortalidad , Biomarcadores de Tumor , Neoplasias del Colon/mortalidad , Redes Reguladoras de Genes , Humanos , Canal de Potasio KCNQ1/genética , Inhibidor 1 de Activador Plasminogénico/genética , Pronóstico , ARN Mensajero/genética , Tropomiosina/genética
14.
Future Oncol ; 15(30): 3467-3481, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31580723

RESUMEN

Aim: Cervical cancer is one of the leading causes of cancer mortality in women. Peripheral white blood cell parameters such as neutrophil (NE), eosinophil (EO), basophil (BA), as well as lymphocyte (LY) and monocyte (MO), are correlated with tumor outcomes. Methods: In total, 110 cervical squamous cell carcinoma patients were recruited in this study. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. Results: Cox regression analysis model indicated that higher pretreatment EO level and increased post-/preradiotherapy EO ratio were independently associated with worse progression-free survival. Lower pretreatment LY or higher EO levels and increased post-/preradiotherapy EO ratio were independently associated with worse overall survival. Conclusion: LY and EO are correlated with outcomes of cervical squamous cell cancer.


Asunto(s)
Carcinoma de Células Escamosas/sangre , Eosinófilos/patología , Linfocitos/patología , Neoplasias del Cuello Uterino/sangre , Adolescente , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Recuento de Linfocitos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugía , Adulto Joven
15.
Acta Pharmacol Sin ; 40(1): 133-142, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30442987

RESUMEN

Berberine, berberrubine, thalifendine, demethyleneberberine, jatrorrhizine, and columbamine are six natural protoberberine alkaloid (PA) compounds that display extensive pharmacological properties and share the same protoberberine molecular skeleton with only slight substitution differences. The oral delivery of most PAs is hindered by their poor bioavailability, which is largely caused by P-glycoprotein (P-gp)-mediated drug efflux. Meanwhile, P-gp undergoes large-scale conformational changes (from an inward-facing to an outward-facing state) when transporting substrates, and these changes might strongly affect the P-gp-binding specificity. To confirm whether these six compounds are substrates of P-gp, to investigate the differences in efflux capacity caused by their trivial structural differences and to reveal the key to increasing their binding affinity to P-gp, we conducted a series of in vivo, in vitro, and in silico assays. Here, we first confirmed that all six compounds were substrates of P-gp by comparing the drug concentrations in wild-type and P-gp-knockout mice in vivo. The efflux capacity (net efflux) ranked as berberrubine > berberine > columbamine ~ jatrorrhizine > thalifendine > demethyleneberberine based on in vitro transport studies in Caco-2 monolayers. Using molecular dynamics simulation and molecular docking techniques, we determined the transport pathways of the six compounds and their binding affinities to P-gp. The results suggested that at the early binding stage, different hydrophobic and electrostatic interactions collectively differentiate the binding affinities of the compounds to P-gp, whereas electrostatic interactions are the main determinant at the late release stage. In addition to hydrophobic interactions, hydrogen bonds play an important role in discriminating the binding affinities.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Berberina/análogos & derivados , Berberina/metabolismo , Animales , Berberina/sangre , Células CACO-2 , Humanos , Enlace de Hidrógeno , Hígado/química , Masculino , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Unión Proteica
16.
Surg Endosc ; 33(10): 3341-3354, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30560498

RESUMEN

BACKGROUND: Robot-assisted gastrectomy (RAG) has been increasingly used for the treatment of advanced gastric cancer (AGC), and many advantages over laparoscopy-assisted gastrectomy (LAG) have been reported. However, its postgastrectomy complications still under investigation and the results remain controversial. This study aimed to objectively assess the incidence and severity of complications following RAG vs. LAG using Clavien-Dindo (C-D) classification and to identify risk factors related to complications. METHODS: Five hundred and twenty-seven patients with AGC who underwent RAG or LAG between January 2016 and May 2018 were enrolled in this study. Complications were categorized according to the C-D classification. The complications following RAG and LAG were compared using one-to-one propensity score matching (PSM) analysis and subgroup analyses. Logistic regression analyses were performed to identify risk factors related to complications. RESULTS: RAG was performed in 251 patients (47.6%) and LAG in 276 patients (52.4%). Before PSM, the RAG group had a smaller tumour size (P = 0.004) and less patients with previous abdominal operation (P = 0.013). After PSM, a well-balanced cohort of 446 patients (223 in each group) was further analyzed. Of interest, the incidence of overall and severe complications (C-D grade ≥ IIIa) following the RAG group were significantly fewer than the LAG group (overall, 24.5% vs. 18.8%, P < 0.001; severe, 8.9% vs. 17.5%, P = 0.002). Subgroup analyses showed statistically significant difference were also observed in most stratified parameters. Multivariable analysis identified age ≥ 65 years, total gastrectomy, stage T3-T4a, stage II-III, and operation time ≥ 250 min as independent predictors of overall complications. Additionally, age ≥ 65 years, stage II-III, and operation time ≥ 250 min were confirmed as independent risk factors for severe complications. CONCLUSIONS: RAG with D2 lymphadenectomy is feasible and safe for the treatment of AGC in terms of the lower incidence and severity of complications.


Asunto(s)
Gastrectomía/efectos adversos , Laparoscopía/efectos adversos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Neoplasias Gástricas/cirugía , Factores de Edad , Anciano , Femenino , Gastrectomía/métodos , Humanos , Incidencia , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/patología
17.
Breast J ; 25(4): 625-630, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31074047

RESUMEN

Disparities in breast cancer treatment have been documented in young and underserved women. This study aimed to determine whether surgical disparities exist among young breast cancer patients by comparing cancer treatment at a public safety-net hospital (BH) and private cancer center (PCC) within a single institution. This was a retrospective study of young women (<45) diagnosed with invasive breast cancer (stage I-III) from 2011-2016. Patient information was abstracted from the breast cancer database at BH and PCC. Demographic variables, surgery type, method of presentation, and stage were analyzed using Pearson's chi-square tests and binary logistic regression. A total of 275 patients between ages 25-45 with invasive breast cancer (Stage I-III) were included in the study. There were 69 patients from BH and 206 patients from PCC. At PCC, the majority of patients were Caucasian (68%), followed by Asian (11%), Hispanic (10%), and African American (8.7%). At BH, patients were mostly Hispanic (47.8%), followed by Asian (27.5%), and African American (10.1%). At PCC, 82% had a college/graduate degree versus 18.6% of patients at BH (P < 0.001). All patients at PCC reported English as their primary language versus 30% of patients at BH (P < 0.001). Patients at PCC were more likely to present with lower stage cancer (P = 0.04), and less likely to present with a palpable mass (P = 0.04). Hospital type was not a predictor of receipt of mastectomy (P = 0.5), nor was race, primary language, or education level. Of patients who received a mastectomy, 87% at BH and 76% at PCC had immediate reconstruction. Surgical management of young women with breast cancer in a public hospital versus private hospital setting was equivalent, even after controlling for race, primary language, stage, and education level.


Asunto(s)
Neoplasias de la Mama/cirugía , Hospitales Privados/estadística & datos numéricos , Hospitales Públicos/estadística & datos numéricos , Adulto , Negro o Afroamericano , Implantación de Mama/estadística & datos numéricos , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Disparidades en Atención de Salud , Hispánicos o Latinos , Humanos , Cobertura del Seguro , Mamoplastia/estadística & datos numéricos , Mastectomía Segmentaria/estadística & datos numéricos , Persona de Mediana Edad , Terapia Neoadyuvante , Ciudad de Nueva York , Estudios Retrospectivos , Factores Socioeconómicos , Población Blanca
18.
Anal Chem ; 90(2): 1136-1141, 2018 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-29251916

RESUMEN

Current achievements on electrochemical monitoring of cells are often gained on two-dimensional (2D) substrates, which fail in mimicking the cellular environments and accurately reproducing the cellular functions within a three-dimensional (3D) tissue. In this regard, 3D scaffold concurrently integrated with the function of cell culture and electrochemical sensing is conceivably a promising platform to monitor cells in real time under their in vivo-like 3D microenvironments. However, it is particularly challenging to construct such a multifunctional scaffold platform. Herein, we developed a 3-aminophenylboronic acid (APBA) functionalized graphene foam (GF) network, which combines the biomimetic property of APBA with the mechanical and electrochemical properties of GF. Hence, the GF network can serve as a 3D scaffold to culture cells for a long period with high viability and simultaneously as an electrode for highly sensitive electrochemical sensing. This allows monitoring of gaseous messengers H2S released from the cells cultured on the 3D scaffold in real time. This work represents considerable progress in fabricating 3D cell culture scaffold with electrochemical properties, thereby facilitating future studies of physiologically relevant processes.


Asunto(s)
Compuestos de Anilina/química , Materiales Biomiméticos/química , Ácidos Borónicos/química , Técnicas de Cultivo de Célula/métodos , Grafito/química , Andamios del Tejido/química , Biomimética , Técnicas Biosensibles/métodos , Adhesión Celular , Proliferación Celular , Técnicas Electroquímicas/métodos , Células HeLa , Humanos , Sulfuro de Hidrógeno/análisis
19.
BMC Gastroenterol ; 18(1): 99, 2018 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-29954326

RESUMEN

BACKGROUND: The classifications and counts of white blood cells (WBCs) have been proved to be able to be used as prognostic markers in cancer cases. The present study investigated the potential values of the classifications and counts of WBC, including lymphocyte (LY), monocyte (MO), neutrophil (NE), eosinophil (EO), and basophil (BA) in the prognosis of resectable gastric cancers (GCs). METHODS: This retrospective study recruited 104 resectable GC cases which were pathologically confirmed. The patients were divided into two groups according to the median pre-treatment values. To evaluate the changes in WBC counts and classification after treatment, we introduced the concept of post/pre-treatment ratios (≤ 1 indicated count was not increased after therapy, while > 1 suggested increased count). RESULTS: Pre-treatment NE and total WBC counts were negatively correlated with overall survival (OS). Surgery significantly decreased the level of NE count, but increased the level of EO, whereas had no effect on the levels of LY, MO, BAor total WBC. Adjuvant chemotherapy significantly decreased the level of BA. Whole course of treatment (surgery combined with adjuvant chemotherapy) had no significant effect on the counts of LY, MO, NE, EO, BA or total WBC. Post/pre-treatment ratios of LY, MO NE, EO, BA and total WBC levels had no effects on OS. Univariate analysis indicated that AJCC stage (III) and higher level of pre-treatment total WBC count were prognostic factors affecting OS. Multivariate Cox regression analysis revealed that AJCC stage (III) and higher level of pre-treatment total WBC count were independent prognostic factors. CONCLUSIONS: Pre-treatment NE count and pre-treatment total WBC count may be potential prognostic factors for the prognostic evaluation of GCs.


Asunto(s)
Neoplasias Gástricas/clasificación , Neoplasias Gástricas/inmunología , Adulto , Anciano , Quimioterapia Adyuvante , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Análisis de Supervivencia
20.
Opt Express ; 25(19): 22375-22387, 2017 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-29041549

RESUMEN

The simultaneous realization of high Q-factor resonances and strong near-field enhancements around and inside of dielectric nanostructures is important for many applications in nanophotonics. However, the incident fields are often confined within dielectric nanoparticles, which results in poor optical interactions with external environment. Near-field enhancements can be extended outside of dielectric nanostructures with proper design, but the Q-factor is often reduced caused by additional radiation losses. This paper shows that the obstacles to achieve high Q-factor, that is, the radiative losses can be effectively suppressed by using dielectric nanodisk arrays, where the Q-factor is about one order larger than that of the single disks associated with the nonradiating anapole modes and the collective oscillations of the arrays. When the resonance energies of the electric dipole mode and the subradiant mode are degenerate with each other, the destructive interference produces an effect analogous to electromagnetically induced transparency. Furthermore, the Q-factor can be extremely enlarged with dielectric split nanodisk arrays, where the present of the split gap does not induce additional losses. Instead, the coupling between the two interfering modes is modified by adjusting the gap width, which makes it possible to achieve high Q-factor and strong near-field enhancements around and inside of the split disks simultaneously. It is shown that the Q-factor is approaching to 106 when the gap width is about 110 nm, and the near-field enhancements around and inside of the split disks are about two orders stronger than that of the single disk.

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