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1.
BMC Pulm Med ; 24(1): 129, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38481241

RESUMEN

BACKGROUND: Previous observational research showed a potential link between physical activities such as walking and the risk of lung cancer. However, Mendelian randomization (MR) studies suggested there was no association between moderate to vigorous physical activity and lung cancer risk. We speculated that specific physical activities may be associated with lung cancer risk. Consequently, we conducted an MR study to examine the potential relationship between walking and the risk of lung cancer. METHODS: We collected genetic summary data from UK Biobank. After excluding SNPs with F values less than 10 and those associated with confounding factors, we conducted a MR analysis to assess the causal effects between different types of walk and lung cancer. We also performed sensitivity analysis to validate the robustness of our findings. Finally, we analyzed the possible mediators. RESULTS: MR analysis showed number of days/week walked for 10 + minutes was associated with a reduced risk of lung cancer risk (OR = 0.993, 95% CI = 0.987-0.998, P = 0.009). Additionally, usual walking pace was identified as a potentially significant factor in lowering the risk (OR = 0.989, 95% CI = 0.980-0.998, P = 0.015). However, duration of walks alone did not show a significant association with lung cancer risk (OR = 0.991, 95%CI = 0.977-1.005, P = 0.216). The sensitivity analysis confirmed the robustness of these findings. And number of days/week walked for 10 + minutes could affect fed-up feelings and then lung cancer risk. There was a bidirectional relationship between usual walking pace and sedentary behaviors (time spent watching TV). CONCLUSION: The study unveiled a genetically predicted causal relationship between number of days/week walked for 10 + minutes, usual walking pace, and the risk of lung cancer. The exploration of potential mediators of walking phenotypes and their impact on lung cancer risk suggests that specific physical activities may reduce the risk of lung cancer.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Análisis de la Aleatorización Mendeliana , Caminata , Ejercicio Físico , Emociones , Estudio de Asociación del Genoma Completo
2.
Genomics ; 115(4): 110662, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37270068

RESUMEN

cfDNA fragmentomic features have been used in cancer detection models; however, the generalizability of the models needs to be tested. We proposed a type of cfDNA fragmentomic feature named chromosomal arm-level fragment size distribution (ARM-FSD), evaluated and compared its performance and generalizability for lung cancer and pan-cancer detection with existing cfDNA fragmentomic features (as reference) by using cohorts from different institutions. The ARM-FSD lung cancer model outperformed the reference model by ∼10% when being tested by two external cohorts (AUC: 0.97 vs. 0.86; 0.87 vs. 0.76). For pan-cancer detection, the performance of the ARM-FSD based model is consistently higher than the reference (AUC: 0.88 vs. 0.75, 0.98 vs. 0.63) in a pan-cancer and a lung cancer external validation cohort, indicating that ARM-FSD model produces stable performance across multiple cohorts. Our study reveals ARM-FSD based models have a higher generalizability, and highlights the necessity of cross-study validation for predictive model development.


Asunto(s)
Ácidos Nucleicos Libres de Células , Trastornos de los Cromosomas , Neoplasias Pulmonares , Humanos , Ácidos Nucleicos Libres de Células/genética , Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Trastornos de los Cromosomas/diagnóstico , Biomarcadores de Tumor/genética
3.
Geriatr Nurs ; 58: 399-409, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38889574

RESUMEN

OBJECTIVE: This study aimed to enhance understanding, engagement, and learning efficiency in the course "The Care of Common Diseases of Older Adults" using a developed Immersive Virtual Reality(IVR) system. METHODS: A mixed-methods study with 32 students was conducted. The quantitative part involved a randomized controlled trial, and the qualitative part included thematic interviews with students and teachers. RESULTS: The intervention group using the IVR system showed significant improvements in positivity and performance evaluation scores (P < 0.05) compared to the control group. Negative affect scores also decreased significantly (P < 0.05). Qualitative data from interviews supported the quantitative findings, highlighting increased curiosity, learning enthusiasm, and academic performance. CONCLUSION: IVR significantly enhances learning by stimulating curiosity and active participation, making education more accessible and improving student performance. Future IVR enhancements should focus on user-friendliness and empathetic feedback in adult care.

4.
J Gerontol Nurs ; 49(11): 25-32, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37906042

RESUMEN

There is a shortage of personnel to provide care for older adults with dementia, and traditional teaching methods could be improved. The teaching method used in the Care for Older Adults With Dementia course is mainly theoretical, lacking real-life care scenarios and practical procedural training. In the current study, we developed a virtual reality (VR) teaching system and designed a randomized controlled trial aimed at testing the availability of the VR-assisted teaching system, filling the gap in teaching through care scenarios, enabling students majoring in intelligent health and oldage care service management to have a more positive attitude toward learning, and improving students' knowledge and course satisfaction. This study showed that the developed VR system can meet the initial needs of daily teaching, help students have a more positive attitude toward learning, and improve their academic performance and course satisfaction. [Journal of Gerontological Nursing, 49(11), 25-32.].


Asunto(s)
Demencia , Enfermería Geriátrica , Realidad Virtual , Humanos , Anciano , Estudiantes , Competencia Clínica , Demencia/terapia
5.
Clin Endocrinol (Oxf) ; 96(5): 680-689, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34970750

RESUMEN

OBJECTIVE: Primary aldosteronism (PA) is a common form of secondary hypertension. Adrenal venous sampling (AVS) is the gold standard for subtyping PA. This study aimed to determine whether there is a difference between immunoassays and liquid chromatography-mass spectrometry (LC-MS/MS) methods for measuring cortisol levels that affect the judgement of AVS. DESIGN: This was a retrospective study. PATIENTS: Included 72 patients who were diagnosed with PA and had undergone AVS. MEASUREMENTS: Patients were grouped according to whether they received adrenocorticotropic hormone (ACTH) stimulation during AVS, and the cortisol results were measured using immunoassay and LC-MS/MS. RESULTS: There were 48 patients in the without ACTH stimulation group and 24 in the post-ACTH stimulation group during AVS (bilateral adrenal vein cannulation success rate, 56.25% vs. 83.33%). ACTH stimulation was beneficial for increasing the success rate of AVS (p < .001). Immunoassays were linearly correlated with LC-MS/MS when cortisol concentrations were <1750 nmol/L (r = .959, p < .001). When cortisol concentrations were >17,500 nmol/L, no correlation was found between the two methods (p = .093). The two methods were consistent for the detection of cortisol for evaluating the success of cannulation for AVS. Five percent of patients showed discordant lateralization of aldosterone production according to the cortisol LC-MS/MS and immunoassay results in the without ACTH group, and 15% showed discordant lateralization in the post-ACTH group. CONCLUSIONS: The immunoassay method can be used to determine whether cannulation is successful. The final decision for lateralization may be more appropriate based on LC-MS/MS results.


Asunto(s)
Hidrocortisona , Hiperaldosteronismo , Glándulas Suprarrenales/irrigación sanguínea , Aldosterona , Cromatografía Liquida , Errores Diagnósticos , Humanos , Hidrocortisona/análisis , Hiperaldosteronismo/diagnóstico , Estudios Retrospectivos , Espectrometría de Masas en Tándem
6.
Cell Immunol ; 365: 104376, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33984534

RESUMEN

Adoptive T cell transfer is one of the most promising ways to combat solid tumors. However, the weak infiltration of T cells into tumor sites has restricted their antitumor efficacy. To overcome this obstacle, we used the lipophilic protein painting strategy to improve tumor targeting and penetrating capacity of lymphocytes for the first time. We synthesized the lipid anchor consisting of a bispecific recombinant protein iRGD-antiEGFR and DSPE-PEG derivates, then successfully inserted it into the membranes of T cells. This surface modification was non-invasive and could efficiently improve the infiltration ability of T cells into multicellular spheroids and tumor masses. The surface modified T cells also displayed superior antitumor activities in EGFR-positive tumor xenografts via systematic infusion. Moreover, the permeability and antitumor efficacy of these surface painted T cells could be remarkably enhanced when used in combination with local low-dose irradiation.


Asunto(s)
Membrana Celular/metabolismo , Inmunoterapia Adoptiva/métodos , Linfocitos Infiltrantes de Tumor/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Anticuerpos de Dominio Único/metabolismo , Neoplasias Gástricas/terapia , Linfocitos T/metabolismo , Animales , Línea Celular Tumoral , Receptores ErbB/inmunología , Receptores ErbB/metabolismo , Ingeniería Genética , Humanos , Lípidos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidiletanolaminas , Polietilenglicoles , Receptores de Antígenos de Linfocitos T/genética , Anticuerpos de Dominio Único/genética , Neoplasias Gástricas/inmunología , Linfocitos T/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Clin Chem Lab Med ; 58(9): 1477-1487, 2020 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-32084000

RESUMEN

Background: Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assays are employed in more and more clinical laboratories to quantify steroids. The steroid quantification by LC-MS/MS shows great value in screening or diagnosing endocrine disorders; however, the number of functional steroids included in the LC-MS/MS methods is still limited. Methods: Here, we describe the performance and validation of a 20-steroid plasma panel by LC-MS/MS. The panel included progestogens (including mineralocorticoids and glucocorticoids), androgens and estrogens biosynthesized in steroid metabolic pathways. The LC-MS/MS method was validated according to guidance documents, and subsequently employed to profile steroid changes in endocrine disorders. Results: Using LC-MS/MS, 20 steroids were separated and quantified in 8 min. Coefficients of variation (CVs) of the 20 analytes at the lower limit of quantification (LLoQ) were all less than 15% (ranging from 1.84% to 14.96%). The linearity of the assay was demonstrated by all the R2 values greater than 0.995. Individual plasma steroids changed significantly in patients with subclinical Cushing's syndrome (SCS) and polycystic ovary syndrome (PCOS) - 17-hydroxypregnenolone (17-OH-PR), testosterone (T) and dihydrotestosterone (DHT) were significantly decreased in SCS patients, while in PCOS patients, pregnenolone, corticosterone (CORT), androstenedione (A4) and T were significantly increased and DHT was decreased. Conclusions: The LC-MS/MS method we developed for the quantification of 20 plasma steroids is clinical practicable. The steroid profiling data using this assay indicate its screening value for endocrine disorders. To further explore the value of the assay, more investigations are however needed.


Asunto(s)
Cromatografía Liquida , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Síndrome del Ovario Poliquístico/sangre , Esteroides/sangre , Espectrometría de Masas en Tándem , Femenino , Humanos , Límite de Detección , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
8.
Bioorg Med Chem ; 27(1): 116-124, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30503410

RESUMEN

BMS-986120 is a PAR4 antagonist that is being investigated as an antiplatelet agent in phase I clinical trial. An improved synthesis of BMS-986120 has been developed. Based on the novel synthetic approach to BMS-986120, a series of deuterated derivatives of BMS-986120 have been synthesized and biologically evaluated to search for more potent antiplatelet agents. The in vitro antiplatelet assay by turbidimetry demonstrated that PC-2 and PC-6 had IC50 values of 6.30 nM and 6.97 nM, respectively, versus BMS-986120 with an IC50 of 7.80 nM. The result of in vitro metabolic stability study showed that all of the deuterated compounds had similar half-life (T1/2) and intrinsic clearance (Clint) in comparison with BMS-986120. Further probing the metabolic profile of BMS-986120 is worth being conducted.


Asunto(s)
Benzofuranos/farmacología , Imidazoles/farmacología , Morfolinas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Receptores de Trombina/antagonistas & inhibidores , Tiazoles/farmacología , Animales , Benzofuranos/síntesis química , Benzofuranos/química , Plaquetas/efectos de los fármacos , Deuterio , Estabilidad de Medicamentos , Humanos , Imidazoles/síntesis química , Imidazoles/química , Masculino , Ratones Endogámicos ICR , Microsomas Hepáticos/metabolismo , Morfolinas/síntesis química , Morfolinas/química , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/síntesis química , Inhibidores de Agregación Plaquetaria/química , Tiazoles/síntesis química , Tiazoles/química
9.
Neurourol Urodyn ; 38(5): 1266-1277, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31006139

RESUMEN

AIM: Diabetic bladder dysfunction (DBD) is one of the most common and bothersome complications of diabetes mellitus (DM). This study aimed to investigate the functional, structural, and molecular changes of the bladder at 0, 3, 6, 9, and 12 weeks after DM induction by streptozotocin (STZ) in male C57BL/6 mice. METHODS: Male C57BL/6J mice were injected with STZ (130 mg/kg). Then, diabetic general characteristics, cystometry test, histomorphometry, and contractile responses to α, ß-methylene ATP, KCl, electrical-field stimulation, carbachol were performed at 0, 3, 6, 9, and 12 weeks after induction. Finally, protein and messenger RNA (mRNA) expressions of myosin Va and SLC17A9 were quantified. RESULTS: DM mice exhibited lower body weight, voiding efficiency and higher water intake, urine production, fasting blood glucose, oral glucose tolerance test, bladder wall thickness, maximum bladder capacity, residual volume, bladder compliance. In particular, nonvoiding contractions has increased more than five times at 6 weeks. And the amplitudes of spontaneous activity, contractile responses to all stimulus was about two times higher at 6 weeks but cut almost in half at 12 weeks. The protein and mRNA expressions of myosin Va and SLC17A9 were about two times higher at 6 weeks, but myosin Va was reverted nearly 40% while SLC17A9 is still higher at 12 weeks. CONCLUSIONS: DBD transitioned from a compensated state to a decompensated state in STZ-induced DM mice at 9 to 12 weeks after DM induction. Our molecular data suggest that the transition may be closely related to the alterations of myosin Va and SLC17A9 expression levels in the bladder with time.


Asunto(s)
Diabetes Mellitus Experimental/patología , Enfermedades de la Vejiga Urinaria/patología , Animales , Peso Corporal , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Ingestión de Líquidos , Estimulación Eléctrica , Prueba de Tolerancia a la Glucosa , Masculino , Ratones , Ratones Endogámicos C57BL , Contracción Muscular/efectos de los fármacos , Cadenas Pesadas de Miosina/biosíntesis , Cadenas Pesadas de Miosina/genética , Miosina Tipo V/biosíntesis , Miosina Tipo V/genética , Proteínas de Transporte de Nucleótidos/biosíntesis , Proteínas de Transporte de Nucleótidos/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Estimulación Química , Enfermedades de la Vejiga Urinaria/etiología , Enfermedades de la Vejiga Urinaria/genética , Urodinámica
10.
BMC Complement Altern Med ; 19(1): 41, 2019 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-30717724

RESUMEN

BACKGROUND: This study aimed to elucidate the effects and mechanisms of Radix Linderae (RL) extracts on a mouse model of diabetic bladder dysfunction (DBD), especially on later decompensated phase. METHODS: Male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) after 4 weeks of high-fat diet (HFD) feeding. DBD mouse models (later decompensated phase) were developed by 12-weeks persistent hyperglycemia and then treated with RL extracts for 4 weeks. During administration, the fasting blood glucose (FBG) test was performed once a week. Four weeks later, oral glucose tolerance test (OGTT), voided stain on paper (VSOP), and urodynamic alteration were explored. We also performed haematoxylin and eosin (H&E) and Masson's trichrome staining to observe the histology of the bladder. Then, the contractile responses to α, ß-methylene ATP, capsaicin (CAP), KCl and carbachol were measured. Moreover, qPCR assay was performed to analyse the bladder gene expression levels of M3 receptors and TRPV1. RESULTS: The diabetic mice exhibited higher FBG, OGTT and urine production, and no substantial alteration was observed after RL treatment. Urodynamic test showed the maximum bladder capacity (MBC), residual volume (RV) and bladder compliance (BC), as well as the decrement of voided efficiency (VE) and micturition volume (MV), remarkably increased in the DBD mice. Furthermore, RL treatment significant improved urodynamic urination, with lower MBC, RV, and, BC, as well as higher VE and MV, as compared with the model groups. The wall thickness of the bladder and the ratio of smooth muscle/collagen remarkably increased, and RL could effectively attenuate the pathological change. The response of bladder strips to the stimulus was also reduced in the DBD mice, and RL treatment markedly increased the contraction. Furthermore, the gene expression levels of M3 receptors and TRPV1 were down-regulated in the bladders of the diabetic mice, whereas RL treatment retrieved those gene expression levels. CONCLUSIONS: RL extracts can improve the bladder voiding functions of the DBD model mice in later decompensated phase, and underlying mechanisms was associated with mediating the gene expression of M3 receptors and TRPV1 in the bladder instead of improving blood sugar levels.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Medicamentos Herbarios Chinos , Lindera/química , Enfermedades de la Vejiga Urinaria/tratamiento farmacológico , Vejiga Urinaria/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Raíces de Plantas , Vejiga Urinaria/patología , Vejiga Urinaria/fisiopatología , Enfermedades de la Vejiga Urinaria/fisiopatología
11.
Cell Immunol ; 334: 78-86, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30392890

RESUMEN

Adoptive immunotherapy is a promising cancer treatment that entails infusion of immune cells manipulated to have antitumor specificity, in vitro. Antigen-specific cytotoxic T lymphocytes are the main executors of transformed cells during cancer immunotherapy. To induce antigen-specific cytotoxic T lymphocytes, we developed artificial antigen-presenting cells (aAPCs) by engineering K562 cells with electroporation to direct the stable expression of HLA-A∗0201, CD80, and 4-1BBL. Our findings demonstrate that after three stimulation cycles, the aAPCs promoted the induction of antigen-specific cytotoxic T lymphocytes with a less differentiated "young" phenotype, which enhanced immune responses with superior cytotoxicity. This novel, easy, and cost-effective approach to inducing antigen-specific cytotoxic T lymphocytes provides the possibility of improved cancer therapies.


Asunto(s)
Presentación de Antígeno/inmunología , Células Presentadoras de Antígenos/inmunología , Antígenos de Neoplasias/inmunología , Células Dendríticas/inmunología , Linfocitos T Citotóxicos/inmunología , Ligando 4-1BB/inmunología , Antígeno B7-1/inmunología , Línea Celular Tumoral , Antígenos HLA-A/inmunología , Humanos , Inmunoterapia Adoptiva/métodos , Células K562 , Activación de Linfocitos/inmunología
12.
Cell Immunol ; 331: 1-8, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29903664

RESUMEN

Adoptive cell therapy (ACT) of autologous tumor-infiltrating lymphocytes (TILs) has shown an effect on mediating tumor regression in some patients with highly advanced, refractory metastatic malignancy. Here, the in vitro generation of TILs isolated from malignant pleural effusion and ascites was compared with which using engineered cells for costimulatory enhancement (ECCE) and 3 common γ-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, alone or in combination. We showed the robust clinical-scale production of TILs with a less differentiated 'young' phenotype by expansion in the presence of ECCE combined with IL-2/7/15. Furthermore, a major fraction of the TILs generated in this fashion was shown to produce much more IFN-γ and TNF-α, and displayed cytolytic activity against target cells expressing the relevant antigens. To our knowledge, this is the first time that the combination of ECCE and IL-2/7/15 has been applied for the generation of TILs isolated from malignant pleural effusion and ascites.


Asunto(s)
Ascitis/inmunología , Activación de Linfocitos/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Derrame Pleural Maligno/inmunología , Ligando 4-1BB/genética , Ligando 4-1BB/inmunología , Ligando 4-1BB/metabolismo , Adulto , Anciano , Ascitis/patología , División Celular/inmunología , Células Cultivadas , Femenino , Humanos , Inmunoterapia Adoptiva/métodos , Interleucina-15/genética , Interleucina-15/inmunología , Interleucina-15/metabolismo , Interleucina-2/genética , Interleucina-2/inmunología , Interleucina-2/metabolismo , Interleucina-7/genética , Interleucina-7/inmunología , Interleucina-7/metabolismo , Células K562 , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia , Derrame Pleural Maligno/patología
13.
Cell Immunol ; 320: 38-45, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28935250

RESUMEN

Blockade of the immune cell checkpoint inhibitors programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a powerful tool in cancer treatment, which is effective across various solid cancer types and hematologic malignancies. Our previous studies showed that by reducing immune tolerance, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) modified cytotoxic T lymphocytes (CTLs) rank highly in terms of immune responses and cytotoxicity. In this study, a genetically modified K562 cell line with surface expression of 4-1BBL was developed to expand PD-1-disrupted CTLs in vitro for further adoptive immunotherapy against cancer. Our findings demonstrate that after a long-term, up to 28days, engineered cells for costimulatory enhancement (ECCE) combined with IL-21 promote the expansion of PD-1-disrupted CTLs with a less differentiated "young" phenotype, enhanced immune response and superior cytotoxic effector characteristics. These new in vitro conditions represent a nimble and cost-effective approach to developing PD-1-disrupted CTLs with improved therapeutic potential.


Asunto(s)
Ligando 4-1BB/genética , Vacunas contra el Cáncer/inmunología , Inmunoterapia Adoptiva/métodos , Interleucinas/uso terapéutico , Neoplasias/terapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Linfocitos T Citotóxicos/inmunología , Ligando 4-1BB/metabolismo , Sistemas CRISPR-Cas , Proliferación Celular , Citotoxicidad Inmunológica , Ingeniería Genética , Humanos , Tolerancia Inmunológica , Células K562 , Activación de Linfocitos , Neoplasias/inmunología , Linfocitos T Citotóxicos/trasplante
14.
Tumour Biol ; 35(8): 7743-54, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24810925

RESUMEN

LncRNA SPRY4-IT1 has been shown to promote the progression of melanoma. However, the role of lncRNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to investigate the clinical significance and biological functions of SPRY4-IT1 in ESCC. The expression levels of lncRNA SPRY4-IT in 92 ESCC patients and 8 ESCC cell lines were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in ESCC cell lines. Both in vitro and in vivo assays were performed to further explore its role in tumor progression. SPRY4-IT1 levels were significantly higher in ESCC tissues and cells than in corresponding adjacent noncancerous tissues and nontumorigenic esophageal epithelial cells, and the ESCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. The multivariate analysis revealed that SPRY4-IT1 expression level is an independent prognostic factor in ESCC patients. In vitro assays demonstrated that knockdown of SPRY4-IT1 reduced cell proliferation, invasiveness, and migration. In vivo assays demonstrated that knockdown of SPRY4-IT1 decreases cell growth. SPRY4-IT1 is a novel molecule involved in ESCC progression, which may provide a potential prognostic biomarker and a potential target for therapeutic intervention.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas del Tejido Nervioso/genética , ARN Largo no Codificante/fisiología , Anciano , Animales , Carcinoma de Células Escamosas/mortalidad , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , ARN Largo no Codificante/genética , Regulación hacia Arriba
15.
Dig Dis Sci ; 59(3): 591-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24337686

RESUMEN

BACKGROUND: Recent studies revealed that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. PlncRNA-1 is one of lncRNAs that is associated with cell apoptosis and proliferation of prostate cancer. AIM: This study aimed to assess the potential role of PlncRNA-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PlncRNA-1 in 73 pairs of ESCC and their matched normal tissues. The correlation of PlncRNA-1 with clinicopathological features and clinical stages was also analyzed. Cancer cell proliferation and apoptosis were assessed following knock-down of PlncRNA-1 by MTT, colony formation assay, and flow cytometry. RESULTS: The expression of PlncRNA-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (69.8 %, p < 0.05), and the high level of PlncRNA-1 expression was significantly correlated with advanced clinical stage (p < 0.01) and lymph node metastasis (p < 0.05). Furthermore, knockdown of PlncRNA-1 reduced cell proliferation and increased the apoptosis in vitro. CONCLUSIONS: PlncRNA-1 plays an important role in ESCC cell proliferation. Overexpression of PlncRNA-1 is correlated with advanced tumor stage and lymph node metastasis, and may serve as a potential prognostic marker and therapeutic target for ESCC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/metabolismo , Regulación hacia Arriba , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Citometría de Flujo , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 43(2): 141-4, 2014 03.
Artículo en Zh | MEDLINE | ID: mdl-24782367

RESUMEN

OBJECTIVE: To develop a method for determination of voglibose contents in its tablets by high-performance liquid chromatography-mass spectrometry (HPLC-MS). METHODS: The measurements were carried out on an Agilent ZORBAX Eclipse Plus C18 column (2.1×150mm 3.2µm) with a temperature of 40 degrees Celsius. A mixture of methanol and water (2:3,v/v) was used as a mobile phase at a flow rate of 0.25 ml/min. Voglibose was detected in an electrospray ionization (ESI) mode with MRM. RESULTS: The calibration curves of voglibose showed good linearity in a range of 1.5804-2.6340 µg/ml (r=0.9990). The average recovery was 100.2% with RSD of 1.37% (n=6) for m/z 268.2/74.2.Linearity was obtained with r=0.9976 and the average recovery was 99.3% with RSD of 1.78% (n=6) for m/z 268.2/92.2. CONCLUSION: HPLC-MS method is accurate,reproducible and can be used for quality control of voglibose tablets.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Inositol/análogos & derivados , Espectrometría de Masas/métodos , Inositol/análisis , Comprimidos
17.
Hum Vaccin Immunother ; 20(1): 2300881, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38214336

RESUMEN

The personalized neoantigen nanovaccine (PNVAC) platform for patients with gastric cancer we established previously exhibited promising anti-tumor immunoreaction. However, limited by the ability of traditional neoantigen prediction tools, a portion of epitopes failed to induce specific immune response. In order to filter out more neoantigens to optimize our PNVAC platform, we develop a novel neoantigen prediction model, NUCC. This prediction tool trained through a deep learning approach exhibits better neoantigen prediction performance than other prediction tools, not only in two independent epitope datasets, but also in a totally new epitope dataset we construct from scratch, including 25 patients with advance gastric cancer and 150 candidate mutant peptides, 13 of which prove to be neoantigen by immunogenicity test in vitro. Our work lay the foundation for the improvement of our PNVAC platform for gastric cancer in the future.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias Gástricas , Vacunas , Humanos , Antígenos de Neoplasias , Neoplasias Gástricas/prevención & control , Epítopos , Péptidos , Inmunoterapia
18.
J Thorac Dis ; 16(5): 2822-2834, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38883611

RESUMEN

Background: Several studies have shown that surgery may improve prognosis in patients with limited-stage small cell lung cancer (LS-SCLC). This study aimed to compare the effects of different treatment modalities on lung cancer specific survival (LCSS) and overall survival (OS) in LS-SCLC patients. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients diagnosed with LS-SCLC. Kaplan-Meier analysis was used to determine the effect of each factor on LCSS and OS. Multivariate analysis was used to analyze the relationship between patient characteristics and survival of different treatment modalities. Results: After a series of screening steps, this study ultimately analyzed the prognosis of patients with stage I-IIIa SCLC under different treatment modalities. The results showed that lobectomy plus postoperative chemoradiotherapy was significantly better than chemoradiotherapy or lobectomy in treatment (all P<0.05). For stage II and IIIA patients, lobectomy plus postoperative chemotherapy ± radiotherapy had similar efficacy to chemoradiotherapy in improving patients' LCSS and OS (all P>0.05), and lobectomy plus postoperative chemotherapy ± radiotherapy did not significantly improve LCSS or OS compared with lobectomy (all P>0.05). Conclusions: For stage II-IIIa SCLC patients, lobectomy might have similar efficacy to chemoradiotherapy in improving LCSS and OS, and there is no need for adjuvant chemotherapy ± radiotherapy after surgery. For stage I SCLC patients, lobectomy plus postoperative chemoradiotherapy might be superior to chemoradiotherapy or lobectomy in improving LCSS and OS; however, the conclusion might be biased. These results suggest that the effect of surgery on SCLC patients may be worthy of further study.

19.
J Med Chem ; 67(7): 5502-5537, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38552183

RESUMEN

Patients with arterial embolic disease have benefited greatly from antiplatelet therapy. However, hemorrhage risk of antiplatelet agents cannot be ignored. Herein, we describe the discovery of 2,3-dihydro[1,4]dioxino[2,3-g]benzofuran compounds as novel PAR4 antagonists. Notably, the isomers 36 and 37 with the chemotype of phenoxyl methylene substituted on the 2,3-dihydro-1,4-dioxine ring exhibited potent in vitro antiplatelet activity (IC50 = 26.13 nM for 36 and 14.26 nM for 37) and significantly improved metabolic stability in human liver microsomes (T1/2 = 97.6 min for 36 and 11.1 min for BMS-986120). 36 also displayed good oral PK profiles (mice: T1/2 = 7.32 h and F = 45.11%). Both of them showed overall potent ex vivo antiplatelet activity at concentrations of 6 and 12 mg/kg, with no impact on the coagulation system and low bleeding liability. Our work will facilitate development of novel PAR4 antagonists as a safer therapeutic option for arterial embolism.


Asunto(s)
Benzofuranos , Trombosis , Humanos , Ratones , Animales , Receptores de Trombina , Inhibidores de Agregación Plaquetaria/metabolismo , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Hemorragia/metabolismo , Coagulación Sanguínea , Trombosis/tratamiento farmacológico , Benzofuranos/uso terapéutico , Agregación Plaquetaria , Receptor PAR-1/metabolismo , Receptor PAR-1/uso terapéutico , Plaquetas/metabolismo
20.
Sci Total Environ ; 924: 171665, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38490406

RESUMEN

Pyrolysis holds immense potential for clean treatment of pulp and paper mill sludge (PPMS), enabling efficient energy and chemical recovery. However, current understanding of PPMS pyrolysis kinetics and product characteristics remains incomplete. This study conducted detailed modeling of pyrolysis kinetics for two typical PPMSs from a wastepaper pulp and paper mill, namely, deinking sludge (PPMS-DS) and sewage sludge (PPMS-SS), and analyzed comprehensively pyrolysis products. The results show that apparent activation energy of PPMS-DS (169.25-226.82 kJ/mol) and PPMS-SS (189.29-411.21 kJ/mol) pyrolysis undergoes significant change, with numerous parallel reactions present. A distributed activation energy model with dual logistic distributions proves to be suitable for modeling thermal decomposition kinetics of both PPMS-DS and PPMS-SS, with coefficient of determination >0.999 and relative root mean square error <1.99 %. High temperature promotes decomposition of solid organic materials in PPMS, and maximum tar yield for both PPMS-DS (53.90 wt%, daf) and PPMS-SS (56.48 wt%, daf) is achieved at around 500 °C. Higher levels of styrene (24.45 % for PPMS-DS and 14.71 % for PPMS-SS) and ethylbenzene (8.61 % for PPMS-DS and 8.33 % for PPMS-SS) are detected in tar and could be used as chemicals. This work shows great potential to propel development of PPMS pyrolysis technology, enabling green and sustainable production in pulp and paper industry.

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