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1.
Hematology ; 28(1): 2219554, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37288810

RESUMEN

BACKGROUND: T cells' function and activation and the immunosuppressive effect of regulatory T cells (Tregs) play a pivotal role in the occurrence and progression of acute myeloid leukemia (AML). In this study, we investigate the expression of T cell activation markers and quantity of Tregs in bone marrow (BM) and peripheral blood (PB) from AML patients and further characterized their correlation with BM leukemic blasts. METHODS: Expression of CD25, CD38, CD69, and HLA-DR on the surfaces of CD4+ and CD8+ T cells and the quantity of Tregs in BM and PB from new diagnosed (ND), relapsed-refractory (RR), complete remission (CR) AML patients were measured via flow cytometry. RESULTS: Compared to normal controls (NC), we found higher proportion of CD4+ CD69+ T cells, CD8+ CD69+ T cells and Tregs in PB. CD8+ CD38+ T cells and CD8+ HLA-DR+ T cells in RR were significantly higher than ND, CR and NC). Tregs were normalized when AML patients achieved CR. Moreover, there was a minor positive correlation between AML blasts and CD8+ CD25+ T cells or Tregs, while AML blasts had a minor negative correlation with CD4+ CD69+ T cells. CONCLUSION: Abnormal activation markers of T cells and Tregs may be involved in the pathological mechanism of ND and RR AML. Our results indicated that CD8+ CD38+ T cells and CD8+ HLA-DR+ T cells might be RR markers of AML patients. Furthermore, Tregs could be used as clinical indicators to evaluate prognosis for AML patients.


Asunto(s)
Médula Ósea , Leucemia Mieloide Aguda , Humanos , Médula Ósea/patología , Linfocitos T CD8-positivos/patología , Regulación hacia Arriba , Leucemia Mieloide Aguda/patología , Antígenos HLA-DR/metabolismo
2.
Front Immunol ; 14: 1129767, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37122734

RESUMEN

Background: Inflammation serves as an essential driver of liver cirrhosis (LC) incidence. Accordingly, a meta-analysis was carried out to explore the association between specific polymorphisms in the interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) genes and the incidence of LC based on comparisons of genotype and allele frequencies. Objectives: To study the relationship between TNF-α rs361525 and IFN-γ rs2430561 polymorphisms and the risk of LC. Methods: A database search was performed for all studies published as of September 10, 2022. The strength of risk relationships was assessed based on odds ratios (ORs) with 95% confidence intervals (CIs). Results: Pooled analyses were conducted for one common TNF-α polymorphism (rs361525) as well as one common IFN-γ polymorphism (rs2430561). Both of these SNPs were identified as LC-related risk factors. Specifically, rs361525 was related to LC incidence in both alcoholic liver cirrhosis (OR: 1.86, 95%CI: 1.03-3.34) and hepatitis B virus (HBV)-related cirrhosis cases (OR: 1.44, 95%CI: 1.00-2.06) when using an allelic contrast model. Moreover, rs2430561 was significantly related to LC in an Asian population (OR: 1.45, 95%CI: 1.13-1.86) and in the context of HBV-related cirrhosis (OR: 1.48, 95%CI: 1.13-1.93) when using an allelic contrast model. Conclusion: These findings indicate that rs361525 and rs2430561 represent LC-related risk factors, although additional large-scale clinical and case-control studies will be vital to confirm these results.


Asunto(s)
Interferón gamma , Cirrosis Hepática , Factor de Necrosis Tumoral alfa , Humanos , Fibrosis , Predisposición Genética a la Enfermedad , Virus de la Hepatitis B , Interferón gamma/genética , Cirrosis Hepática/genética , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/genética
3.
Immunohorizons ; 6(6): 344-355, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35697478

RESUMEN

Epitope mapping of the interactions between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Abs is challenging because of complexity in protein three-dimensional structures. Protein structure fingerprint technology was applied for epitope mapping of 44 SARS-CoV-2 Abs with three-dimensional structure complexes. The results defined how the epitopes were distributed on SARS-CoV-2 and how the patterns of six CDRs from Abs participated in neutralization. Also, the residue-residue recognition revealed that certain residues had higher frequencies on the interfaces between SARS-CoV-2 and Abs, and the activity correlated with the physicochemical properties of the residues at the interface. Thus, epitope mapping provides significant lead information for development of epitope-based designs for Abs, vaccines, and diagnostic reagents. This is a bioinformatics project of structural data analysis; no animals or cells were used.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Mapeo Epitopo , Epítopos , Humanos , Glicoproteínas de Membrana , Glicoproteína de la Espiga del Coronavirus , Proteínas del Envoltorio Viral
4.
Immun Inflamm Dis ; 9(4): 1428-1438, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34647429

RESUMEN

INTRODUCTION: Diabetic foot ulcer infection (DFI) is an infectious disease of the skin and soft tissue in diabetics notorious for making rapid progress and being hard to cure. Staphylococcus aureus (S. aureus), most frequently detected in DFI, recently was suggested as an intracellular pathogen that can invade and survive within mammalian host cells. Autophagy in macrophages plays a vital immune role in combating intracellular pathogens through bacterial destruction, but there is a lack of empirical research about the infection characteristics and autophagy in diabetic skin infection. METHODS: Here, we used streptozotocin-induced Sprague Dawley rats as a diabetic skin wound model to examine the S. aureus clearance ability and wound healing in vitro. Western blot and immunofluorescence staining were used to evaluate the autophagic flux of the macrophages in diabetic rats dermis, even with S. aureus infection. RESULTS: We demonstrated that infections in diabetic rats appeared more severe and more invasive with weakened pathogen clearance ability of the host immune system, which coincided with the suppressed autophagic flux in dermal macrophages, featured by a significant increase in endogenous LC3II/I and in p62. CONCLUSIONS: Our results first provided convincing evidence that autophagy of macrophages was dysfunctional in diabetes, especially after being infected by S. aureus, which weakens the intracellular killing of S. aureus, potentially worsens the infections, and accelerates the infection spread in the diabetic rat model. Further understanding of the special immune crosstalk between diabetes host and S. aureus infection through autophagic factors will help to explain the complex clinical phenomenon and guarantee the development of effective therapies for diabetic foot infections.


Asunto(s)
Diabetes Mellitus Experimental , Infecciones Estafilocócicas , Animales , Autofagia , Macrófagos , Ratas , Ratas Sprague-Dawley , Staphylococcus aureus , Estreptozocina/toxicidad
5.
Front Immunol ; 12: 642120, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34017330

RESUMEN

Background: Immunological failure during pregnancy is considered one of the etiologies of recurrent miscarriage (RM). The decreased production of mixed lymphocyte reaction-blocking factors (MLR-Bf) may play a major role in this condition. Lymphocyte immunotherapy (LIT), which induces the production of MLR-Bf, has been used in treating RM patients since 1984. However, the effectiveness of LIT is currently being heatedly debated. In addition to that, possible changes to the maternal immune system upon induced MLR-Bf production by LIT remains unclear. Objectives: To explore the possible impacts that MLR-Bf may have on the expression of immune biomarkers and pregnancy outcomes, and deduce whether the prevention of miscarriages is possible with LIT or MLR-Bf in RM patients. Materials and Methods: Women with previous early RM (eRM) were enrolled in this retrospective study after they got pregnant again. LIT was implemented before pregnancy and during the first trimester. MLR-Bf and immune biomarkers were checked as the clinical routine. Patients were followed up until 12 gestational weeks. Levels of immune biomarkers and successful pregnancy rates were compared between MLR-Bf- group and MLR-Bf+ group stratified by LIT. Independent associations between LIT, or MLR-Bf, and miscarriage were estimated. All data management and analysis were conducted using SPSS 20.0. Results: A total of 1,038 patients, 497 MLR-Bf- (49 cases accepted LIT), and 541 MLR-Bf+(463 cases induced by LIT) were included in the study. Percentage of lymphocytes, the ratio of CD4+ T cells/lymphocytes, and levels of some rheumatoid biomarkers (anti-U1-nRNP, anti-SAA-52kd, and anti-CENOP B) were statistically higher in MLR-Bf+ group than in MLR-Bf- group among women without LIT. With LIT treatment the successful pregnancy rate was statistically higher in MLR-Bf+ group than in MLR-Bf- group (66.7% vs. 51.0%, P = 0.028) among women with LIT. Meanwhile, LIT was estimated to have an independent negative association with miscarriage. Conclusion: Upon LIT treament levels of immune biomarkers were different in women with and without MLR-Bf when stratified by whether they received LIT. Not MLR-Bf, but LIT, has an independent protective effect on miscarriage.


Asunto(s)
Aborto Habitual/terapia , Anticuerpos Bloqueadores/uso terapéutico , Inmunoterapia/métodos , Transfusión de Linfocitos/métodos , Resultado del Embarazo , Aborto Habitual/inmunología , Biomarcadores/análisis , Femenino , Humanos , Inmunoglobulina G/uso terapéutico , Embarazo , Estudios Retrospectivos
6.
Ann Palliat Med ; 9(2): 359-367, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32233631

RESUMEN

BACKGROUND: To establish a stable ex vivo lung perfusion (EVLP) model and determine the preservation effect of the EVLP technique on donor lungs in vitro. METHODS: EVLP was performed on nonacceptable human donor and porcine lungs, and during perfusion, the oxygenation index was assessed and blood gas analysis was performed. RESULTS: After 4 h of EVLP of nonacceptable human donor and porcine lungs, lung function parameters remained stable, and lung energy metabolism was improved to a certain extent. CONCLUSIONS: EVLP can suitably maintain donor lungs in vitro for transplantation and is an effective method for ex vivo preservation of donor lungs.


Asunto(s)
Trasplante de Pulmón/métodos , Perfusión/métodos , Obtención de Tejidos y Órganos/métodos , Animales , Humanos , Soluciones Preservantes de Órganos , Preservación Biológica , Porcinos , Recolección de Tejidos y Órganos/métodos
7.
Cytokine ; 126: 154868, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31629110

RESUMEN

Lung cancer is a common malignant disease, nearly 2.09 million new patients occurred last year. Approximately 85% of the patients are classified as non-small-cell lung cancer (NSCLC). It is therefore important to identify new diagnostic and prognostic biomarkers for the early detection of this disease. The presented study identifies biomarkers in the serum of NSCLC patients. The expression of 274 cytokines was measured by a novel antibody array methodology and ELISA was applied to validate the array results. The levels of MIP-1 α, IL-8, MIP-1 ß, Resistin, GDF-15, HGF, CA125, FLRG, VCAM-1, DKK-3, sTNF-R1, CTACK, Acrp30, CXCL-16 and LYVE-1 were significantly higher in serum from NSCLC patients, while the level of TIMP-2 and IGFBP-6 were lower. More importantly, the validation supported the result of the antibody array. The result of the antibody array indicates that these cytokines might be novel auxiliary biomarkers in the diagnosis and prognosis of NSCLC.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Citocinas/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Adulto , Anticuerpos , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Quimiocina CCL3/sangre , Quimiocina CCL3/genética , Citocinas/genética , Regulación hacia Abajo , Femenino , Humanos , Inmunohistoquímica , Proteína 6 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 6 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Análisis por Matrices de Proteínas , Reacción en Cadena en Tiempo Real de la Polimerasa , Inhibidor Tisular de Metaloproteinasa-2/sangre , Inhibidor Tisular de Metaloproteinasa-2/genética , Regulación hacia Arriba
8.
Hematology ; 24(1): 473-479, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31142214

RESUMEN

Introduction: CD19+CD24hiCD38hi regulatory B cells (Bregs) and CD19+CD27+ memory B cells (Bmems) are B cell subsets with specific immunoregulatory properties. In this study, the balance of these subsets was investigated in pediatric immune thrombocytopenia (ITP) patients, and the frequencies of Bregs and Bmems before and after first-line therapy were measured. Methods: Forty-nine pediatric ITP patients and 19 normal controls were enrolled in this study. The total CD19+ B cells, Bregs and Bmems in the peripheral blood (PB) of all cases were measured by flow cytometry. Results: We found higher frequencies of total CD19+ B cells and Bmems in newly diagnosed ITP patients than those in normal controls (p < 0.01), whereas the frequencies of CD19+CD24hiCD38hi Bregs was significantly lower in ITP patients (p < 0.001). After therapy with MP + IVIG, the level of CD19+CD24hiCD38hi Bregs and Bmems were almost normalized. Conclusion: Our results indicated that pediatric ITP patients were characterized by a decline in CD19+CD24hiCD38hi Bregs and increment of CD19+CD27+Bmems, and an increase of total CD19+ B cells in their peripheral blood.


Asunto(s)
Linfocitos B Reguladores/metabolismo , Trombocitopenia/genética , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Trombocitopenia/patología
9.
Hematology ; 23(10): 823-827, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29996743

RESUMEN

OBJECTIVES: To investigate the immune status of children with very severe aplastic anemia (VSAA), and evaluate the frequencies of CD20+ B cells and Regulatory T cells (Tregs) as potential markers for evaluating the therapeutic efficacy and prognosis. METHODS: We systematically analyzed CD20+ B cells and Tregs using Flow Cytometry in 36 children with VSAA (14 newly diagnosed cases and 22 cases in remission after therapy with HDIVIG + r-ATG + CSA). RESULTS: In newly diagnosed VSAA patients, the percentage of CD20+ B cells was higher than that in healthy children (P < .01), whereas the percentage of Tregs was lower than that in healthy children (P < .001). After treatment with HDIVIG + r-ATG + CSA, the percentage of CD20+ B cells in peripheral blood was decreased obviously, and the percentage of Tregs was significantly increased. CONCLUSION: There is a moderate negative correlation between the percentage of Tregs and CD20+ B cells in our study. Our results shed light on the roles of Tregs and CD20+ B cells as therapeutic efficacy and prognostic markers of pediatric VSAA. Moreover, the mechanism underlying the decrease of blood Tregs and increase of CD20+ B cells in pediatric VSAA patients have been discussed, indicating that Tregs may suppress B cell responses.


Asunto(s)
Anemia Aplásica , Antígenos CD20 , Suero Antilinfocítico/administración & dosificación , Linfocitos B , Ciclosporina/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Linfocitos T Reguladores , Adolescente , Anemia Aplásica/sangre , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/inmunología , Antígenos CD20/sangre , Antígenos CD20/inmunología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Biomarcadores/sangre , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Índice de Severidad de la Enfermedad , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo
10.
Exp Ther Med ; 14(6): 6084-6086, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29285161

RESUMEN

A patient with acquired hemophilia A (AHA) with hemorrhagic pericardial effusions was admitted to Xiamen Chang Gung Hospital (Xiamen, China) in August 2015. The patient had been experiencing progressive dyspnea for 1 week. Bloody effusion (~6.3 l) was drained from the membrane surrounding the heart over a period of 20 days. Biochemical, cytological and radiological examinations were unable to elucidate the reason for the effusion. Coincidentally, it was discovered that activated partial thromboplastin time prolongation could not be corrected by plasma mixing. Furthermore, immunologic and functional assays identified that the patient had factor VIII-deficient plasma. Finally, the coagulopathy was treated by infusion of cryoagglutinin and steroids to eradicate the coagulation inhibitor. The production of cardiac bloody effusions did not recur. Notably, the patient was diagnosed with AHA accompanied by the rare complication of pericardial effusions. The present case was the first to report AHA with the complication of pericardial effusions.

11.
Artículo en Inglés | MEDLINE | ID: mdl-28712867

RESUMEN

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

12.
J Craniomaxillofac Surg ; 45(8): 1112-1116, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28679471

RESUMEN

BACKGROUND: Endoscopically assisted selective neck dissection (SND) has recently been applied in clinical N0 cases of oral squamous cell carcinoma (OSCC). However, nothing is known of the immune response after surgery. METHODS: A total of 60 patients with cT1-2N0 OSCC randomly underwent endoscopically assisted SND and open operations. The serum levels of IL-6, IL-8, IL-10, IL-1b, TNF-a, CRP, cortisol, ACTH, and growth hormone were analyzed before the start of the surgery (T0) and at 2 (T1), 6 (T2), 24 (T3), and 72 h (T4) after surgery. RESULTS: A total of 31 patients were randomized for endoscopic SND, whereas 29 underwent open procedures. The release of IL-6, IL-10 and CRP was significantly lower in the endoscopic group than in the open surgery group (p < 0.05), and cortisol levels were also lower in the endoscopic group (p < 0.05). CONCLUSIONS: Endoscopic SND could effectively provide lower inflammatory responses and surgical stress, reducing peri-operative trauma and accelerating recovery.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Endoscopía , Neoplasias de la Boca/cirugía , Disección del Cuello , Complicaciones Posoperatorias/inmunología , Estrés Fisiológico/inmunología , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Disección del Cuello/métodos , Estadificación de Neoplasias , Complicaciones Posoperatorias/sangre , Estudios Prospectivos
13.
Jpn J Infect Dis ; 70(5): 528-535, 2017 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-28367875

RESUMEN

Non-specific symptoms and low viremia levels make early diagnosis of dengue virus (DENV) infection challenging. This study aimed to i) identify laboratory markers that can be used to predict a DENV-positive diagnosis and ii) perform a molecular characterization of DENVs from the 2014 Guangdong epidemic. This retrospective study analyzed 1,044 patients from the Guangdong epidemic who were clinically suspected cases of dengue. Viral RNA was detected by real-time RT-PCR, and viral-specific NS1 antigen was detected using enzyme-linked immuno sorbent assay. A molecular phylogenetic analysis was performed for the with the DENV C-prM gene junction. Patients with dengue infection had leukopenia (2.8 × 109/L), thrombocytopenia (109.0 × 109/L), elevated aspartate aminotransferase (56.0 IU/L) and alanine aminotransferase (43.5 IU/L), and prolonged activated partial thromboplastin time (APTT, 33.5 s) (all P < 0.001) compared to patients without dengue. The positive predictive value of leukopenia and thrombocytopenia for DENV infection were 96.9% and 93.0%, respectively. Leukopenia, thrombocytopenia, elevated aminotransferases, and prolonged APTT were useful predictive markers for an early diagnosis of DENV infection. Phylogenetic analysis indicated that the DENVs from the 2014 epidemic were closely related to a 2010 New Delhi strain and a 2013 Guangzhou strain. The 2014 epidemic consisted of co-circulating DENV-1 genotypes I and V from multiple origins. Efficient dengue surveillance can facilitate rapid response to future outbreaks.


Asunto(s)
Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Dengue/epidemiología , Pruebas Diagnósticas de Rutina/métodos , Brotes de Enfermedades , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Técnicas de Laboratorio Clínico/métodos , Dengue/patología , Dengue/virología , Virus del Dengue/genética , Virus del Dengue/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , Valor Predictivo de las Pruebas , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Adulto Joven
14.
Oncol Lett ; 13(3): 1370-1378, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28454264

RESUMEN

Ribosomal S6 kinases (RSKs) are directly regulated by extracellular signal-regulated kinase (ERK) signaling and are implicated in cell growth, survival, motility and senescence. The present study observed that RSK1 was overexpressed in primary untreated leukemia patient bone marrow samples compared with the expression at the complete remission stage, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a high RSK1 expression (relative expression ≥10) was associated with a significantly shorter overall survival (P=0.038) compared with that in patients with low RSK1 expression (relative expression <10). The current study also investigated the effect of luteolin, a novel p90 ribosomal S6 kinase (RSK) inhibitor extracted from Reseda odorata L., which shows strong biochemical functions including anti-allergy, anti-inflammation and anti-cancer functions, in MOLM-13 and Kasumi-1 leukemic cells. The cell viability, apoptosis and migration ability analysis were assessed by performing a cell counting kit-8 assay, Annexin V-FITC/PI double staining and migration filter assay, respectively. The results indicated that luteolin inhibited the growth of the leukemic cell lines through induction of apoptosis, while the migration ability was also suppressed. Overexpression of RSK1 by plasmid transfection was found to decrease the luteolin-induced apoptosis and migration capabilities. By contrast, knockdown of the RSK1 expression by small interfering RNA appeared to induce the same effect as luteolin on MOLM-13 and Kasumi-1 leukemic cells. In conclusion, these results suggest that luteolin inhibits leukemic cell proliferation and induces apoptosis by inhibition of the RSK1 pathways.

15.
Acta Pharmacol Sin ; 38(3): 382-391, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28042875

RESUMEN

Aberrant activation of the PI3K/Akt/mTOR pathway contributes to the proliferation of malignant cells, and may confer resistance to chemotherapy in various malignancies, including acute myeloid leukemia (AML). Chemoresistance is the major reason for relapse in AML. RAD001 (everolimus) has been used at d1 and d7 of an induction chemotherapy regimen for AML, which has acceptable toxicity and may improve conventional chemotherapeutic treatment. Dual inhibitors of PI3K and mTOR overcome some of the intrinsic disadvantages of rapamycin and its derivatives. In this study, we evaluated the effects of BEZ235, a PI3K/mTOR dual inhibitor, on the multidrug-resistant AML cell lines HL-60/VCR and K562/ADR in vitro. BEZ235 dose-dependently inhibited the viability of HL-60/VCR and K562/ADR cells with the IC50 values of 66.69 and 71.44 nmol/L, respectively. BEZ235 (25-100 nmol/L) dose-dependently inhibited the migration of the two AML cell lines, and it also significantly sensitized the two AML cell lines to VCR and ADR. After treatment with BEZ235, the miR-1-3p levels were markedly increased in HL-60/VCR cells. Using TargetScan analysis and luciferase assays, we showed that miR-1-3p targeted BAG4, EDN1 and ABCB1, the key regulators of cell apoptosis, migration and multidrug resistance, and significantly decreased their levels in the two AML cell lines. Transfection of HL-60/VCR and K562/ADR cells with miR-1-3p-AMO to inhibit miR-1-3p could reverse the anti-proliferation effects of BEZ235. In conclusion, the PI3K/mTOR dual inhibitor BEZ235 effectively chemosensitizes AML cells via increasing miR-1-3p and subsequently down-regulating BAG4, EDN1 and ABCB1.


Asunto(s)
Antineoplásicos/farmacología , Imidazoles/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/farmacología , Quinolinas/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Línea Celular Tumoral/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Endotelina-1/metabolismo , Humanos , MicroARNs/metabolismo
16.
Cell Biol Int ; 41(1): 16-23, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27677634

RESUMEN

Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (TKIs) have improved chronic myeloid leukemia (CML) patient survival markedly but fail to eradicate quiescent CML leukemia stem cells (LSCs). Thus, strategies targeting LSCs are required to induce long-term remission and achieve cure. Here, we investigated the ability of topoisomerase II (Top II) inhibitor etoposide (Eto) to target CML LSCs. Treatment with Eto combined with IM markedly induced apoptosis in primitive CML CD34+ CD38- stem cells resistant to eradication by IM alone, but not in normal hematopoietic stem cells, CML and normal mature CD34- cells, and other leukemia and lymphoma cell lines. The interaction of IM and Eto significantly inhibited phosphorylation of PDK1, AKT, GSK3, S6, and ERK proteins; increased the expression of pro-apoptotic gene Bax; and decreased the expression of anti-apoptotic gene c-Myc in CML CD34+ cells. Top II inhibitors treatment represents an attractive approach for targeting LSCs in CML patients undergoing TKIs monotherapy.


Asunto(s)
Etopósido/farmacología , Mesilato de Imatinib/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Células Madre Neoplásicas/patología , Inhibidores de Topoisomerasa II/farmacología , Antígenos CD34/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Etopósido/uso terapéutico , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Humanos , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Ensayo de Tumor de Célula Madre
17.
Exp Ther Med ; 12(5): 2811-2814, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27882078

RESUMEN

Osteopetrosis is a rare bone disease caused by metabolic imbalances as a result of genetic mutations. For instance, autosomal dominant osteopetrosis is caused by a missense mutation of the C1CN7 gene. This was first reported in 1904 and is thought to be caused by osteoclastic dysfunction and an impaired bone resorption ability. An accumulation of cortical bone mass during the remodeling of the medullary bone may increase the bone density and give rise to a hard marble consistency. Osteopetrosis can be divided into benign and malignant forms; however, no curative treatment exists for benign osteopetrosis. The management of complications, such as chronic osteomyelitis and fractures, serves a key role in influencing the patient survival rates. Previous studies have demonstrated that a combined treatment of hyperbaric oxygen (HBO) lavage for debridement of the necrotic region and high-dose systemic antibiotics may be effective in the management of osteopetrosis. The present study reported a case of chronic mandible osteomyelitis and fistula occurring in association with maxillary sinusitis, who was successfully treated by through nasal endoscopy, using repeated flushing and cleaning every 2 weeks as a form of debridement, in the absence of high-dose antibiotics and HBO.

18.
Int J Biochem Cell Biol ; 79: 337-344, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27613572

RESUMEN

During bioethanol fermentation process, Saccharomyces cerevisiae cell membrane is the first target to be attacked by the accumulated ethanol. In such a prominent position, S. cerevisiae cell membrane could reversely provide protection through changing fluidity or elasticity secondary to remodeled membrane components or structure during the fermentation process. However, there is yet to be a direct observation of the real effect of the membrane compositional change. In this study, atomic force microscope-based strategy was performed to determine Young's modulus of S. cerevisiae to directly clarify ethanol stress-associated changes and roles of S. cerevisiae cell membrane fluidity and elasticity. Cell survival rate decreased while the cell swelling rate and membrane permeability increased as ethanol concentration increased from 0% to 20% v/v. Young's modulus decreased continuously from 3.76MPa to 1.53MPa while ethanol stress increased from 0% to 20% v/v, indicating that ethanol stress induced the S. cerevisiae membrane fluidity and elasticity changes. Combined with the fact that membrane composition varies under ethanol stress, to some extent, this could be considered as a forced defensive act to the ethanol stress by S. cerevisiae cells. On the other hand, the ethanol stress induced loosening of cell membrane also caused S. cerevisiae cell to proactively remodel membrane to make cell membrane more agreeable to the increase of environmental threat. Increased ethanol stress made S. cerevisiae cell membrane more fluidized and elastic, and eventually further facilitated yeast cell's survival.


Asunto(s)
Módulo de Elasticidad/efectos de los fármacos , Etanol/farmacología , Microscopía de Fuerza Atómica , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacos , Adaptación Fisiológica/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Permeabilidad de la Membrana Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Fluidez de la Membrana/efectos de los fármacos , Saccharomyces cerevisiae/fisiología
19.
Clin Lab ; 62(11): 2241-2247, 2016 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28164685

RESUMEN

BACKGROUND: As focus grows on reproduction, the issue of Recurrent Spontaneous Abortion (RSA), especially for unexplained reasons (URSA), is grabbing more and more attention in gynecological immunology. We investigated the changes of peripheral lymphocyte subsets focusing on whether they had some relationship with development of URSA. METHODS: The percentage and absolute count of lymphocyte subsets (T cells, Th cells, Ts cells, B cells, NK cells) were simultaneously evaluated by flow cytometry in URSA patients (n = 48) and healthy controls (HC, n = 22). RESULTS: Significantly lower percentage and absolute counts of NKT cells and NK cells were observed in URSA compared to the HC. After medical therapy, an obviously increase was shown in the percentage of both T cells and B cells, whereas it presented a reduction in the percentage of NK cells. CONCLUSIONS: The flow cytometry test in T, B, NK cells is a method available to identify URSA patients from healthy women and to provide reference guides for clinical therapy.


Asunto(s)
Aborto Habitual/inmunología , Células Asesinas Naturales/inmunología , Aborto Habitual/sangre , Aborto Habitual/diagnóstico , Aborto Habitual/terapia , Adulto , Subgrupos de Linfocitos B/inmunología , Estudios de Casos y Controles , Regulación hacia Abajo , Femenino , Citometría de Flujo , Humanos , Recuento de Linfocitos , Valor Predictivo de las Pruebas , Embarazo , Pronóstico , Subgrupos de Linfocitos T/inmunología , Adulto Joven
20.
J Clin Lab Anal ; 30(3): 208-15, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-25600684

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second leading cause of cancer-related deaths worldwide. The poor prognosis of HCC is mainly because of its discovery at advanced stages. Because chronic hepatitis B (CHB) accounts for 50-80% HCC occurrence worldwide, and immunity is regarded as an emerging hallmark of cancer, we investigated the predictive role of peripheral immune cells in HCC incidence in CHB patients. METHODS: This investigation collected and analyzed data from 89 CHB patients, 94 primary HCC patients with hepatitis B virus (HBV), 81 primary HCC patients without HBV, 69 normal healthy patients, and 257 CHB patients with at least 3-year regular followup. RESULTS: The results demonstrated that CHB and primary HCC patients had different concentrations of lymphocytes, neutrophils, and monocytes in their peripheral circulation. Further study showed that the peripheral lymphocyte concentration was an independent prognostic factor for HCC incidence in CHB patients during the 3 years of followup. Finally, a predictive HCC incidence model with an AUROC (area under the receiver operating characteristic) of 0.832 was constructed based on the peripheral lymphocyte concentration, serum alpha-fetoprotein (AFP) concentration, and cirrhosis status of CHB patients. CONCLUSIONS: The peripheral lymphocyte concentration was an independent prognostic factor for HCC incidence in CHB patients, and a more accurate predictive model based on peripheral lymphocytes, serum AFP, and cirrhosis status was constructed.


Asunto(s)
Carcinoma Hepatocelular/sangre , Progresión de la Enfermedad , Hepatitis B Crónica/sangre , Neoplasias Hepáticas/sangre , Linfocitos/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/epidemiología , Femenino , Humanos , Incidencia , Cirrosis Hepática/sangre , Neoplasias Hepáticas/epidemiología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Monocitos/patología , Análisis Multivariante , Neutrófilos/patología , Pronóstico , Modelos de Riesgos Proporcionales , Adulto Joven , alfa-Fetoproteínas/metabolismo
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