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1.
Sci Rep ; 14(1): 7666, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561384

RESUMEN

Hepatocellular carcinoma (HCC) is a malignancy with poor prognosis. Abnormal expression of H3-H4 histone chaperones has been identified in many cancers and holds promise as a biomarker for diagnosis and prognosis. However, systemic analysis of H3-H4 histone chaperones in HCC is still lacking. Here, we investigated the expression of 19 known H3-H4 histone chaperones in HCC. Integrated analysis of multiple public databases indicated that these chaperones are highly expressed in HCC tumor tissues, which was further verified by immunohistochemistry (IHC) staining in offline samples. Additionally, survival analysis suggested that HCC patients with upregulated H3-H4 histone chaperones have poor prognosis. Using LASSO and Cox regression, we constructed a two-gene model (ASF1A, HJURP) that accurately predicts prognosis in ICGC-LIRI and GEO HCC data, which was further validated in HCC tissue microarrays with follow-up information. GSEA revealed that HCCs in the high-risk group were associated with enhanced cell cycle progression and DNA replication. Intriguingly, HCCs in the high-risk group exhibited increased immune infiltration and sensitivity to immune checkpoint therapy (ICT). In summary, H3-H4 histone chaperones play a critical role in HCC progression, and the two-gene (ASF1A, HJURP) risk model is effective for predicting survival outcomes and sensitivity to immunotherapy for HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Chaperonas de Histonas/metabolismo , Histonas/genética , Histonas/metabolismo , Neoplasias Hepáticas/genética , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Pronóstico
2.
Acad Radiol ; 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38458887

RESUMEN

BACKGROUND: Gliomas are the most common primary brain tumours and constitute approximately half of all malignant glioblastomas. Unfortunately, patients diagnosed with malignant glioblastomas typically survive for less than a year. In light of this circumstance, genotyping is an effective means of categorising gliomas. The Ki67 proliferation index, a widely used marker of cellular proliferation in clinical contexts, has demonstrated potential for predicting tumour classification and prognosis. In particular, magnetic resonance imaging (MRI) plays a vital role in the diagnosis of brain tumours. Using MRI to extract glioma-related features and construct a machine learning model offers a viable avenue to classify and predict the level of Ki67 expression. METHODS: This study retrospectively collected MRI data and postoperative immunohistochemical results from 613 glioma patients from the First Affliated Hospital of Nanjing Medical University. Subsequently, we performed registration and skull stripping on the four MRI modalities: T1-weighted (T1), T2-weighted (T2), T1-weighted with contrast enhancement (T1CE), and Fluid Attenuated Inversion Recovery (FLAIR). Each modality's segmentation yielded three distinct tumour regions. Following segmentation, a comprehensive set of features encompassing texture, first-order, and shape attributes were extracted from these delineated regions. Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) algorithm with subsequent sorting to identify the most important features. These selected features were further analysed using correlation analysis to finalise the selection for machine learning model development. Eight models: logistic regression (LR), naive bayes, decision tree, gradient boosting tree, and support vector classification (SVM), random forest (RF), XGBoost, and LightGBM were used to objectively classify Ki67 expression. RESULTS: In total, 613 patients were enroled in the study, and 24,455 radiomic features were extracted from each patient's MRI. These features were eventually reduced to 36 after LASSO screening, RF importance ranking, and correlation analysis. Among all the tested machine learning models, LR and linear SVM exhibited superior performance. LR achieved the highest area under the curve score of 0.912 ± 0.036, while linear SVM obtained the top accuracy with a score of 0.884 ± 0.031. CONCLUSION: This study introduced a novel approach for classifying Ki67 expression levels using MRI, which has been proven to be highly effective. With the LR model at its core, our method demonstrated its potential in signalling a promising avenue for future research. This innovative approach of predicting Ki67 expression based on MRI features not only enhances our understanding of cell activity but also represents a significant leap forward in brain glioma research. This underscores the potential of integrating machine learning with medical imaging to aid in the diagnosis and prognosis of complex diseases.

3.
Anticancer Res ; 42(7): 3325-3340, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35790295

RESUMEN

BACKGROUND/AIM: Intestinal stem cells (ISCs) are responsible for intestinal proliferation, differentiation, and neoplasia, and also play a crucial role in inflammation. Thus, it is important to investigate the effect of TNF-α on the activities of NF-κB, PI3K/Akt, and Wnt/ß-catenin signaling pathways. MATERIALS AND METHODS: The Lgr5+ intestinal cells were isolated using fluorescence-activated cell sorting from NCM460 spheroid cells, and the potential molecular mechanisms were investigated via short hairpin RNA (shRNA) transfection or the use of an inhibitor. RESULTS: The Lgr5+ cells were termed ISCs because of the higher expression of stem cell genes, including Sox2, Nanog, Oct4, Lgr5, and CD133. The Lgr5+ ISCs had a higher proliferation capacity, invasive ability, and drug resistance to 5-fluorouracil, as well as higher expression levels of anti-apoptotic proteins but lower expression levels of pro-apoptotic proteins, compared with Lgr5~ cells. The PI3K/Akt and Wnt/ß-catenin pathways were triggered by the TNF-α-induced activation of NF-κB signaling. Notably, when p65 expression was knocked-down via shRNA transfection in Lgr5+ ISCs, the TNF-α-induced activation of the NF-κB, PI3K/Akt, and Wnt/ß-catenin pathways were reversed. The same effect was observed with regards to ß-catenin shRNA transfection. Moreover, the Akt inhibitor MK2206 inhibited the TNF-α-induced activation of the PI3K/Akt pathway, as well as the NF-κB and Wnt/ß-catenin pathways. CONCLUSION: PI3K/Akt and Wnt/ß-catenin signaling cross-regulate NF-κB signaling in TNF-α-induced human Lgr5+ ISCs.


Asunto(s)
FN-kappa B , beta Catenina , Humanos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ARN Interferente Pequeño , Receptores Acoplados a Proteínas G/genética , Células Madre , Factor de Necrosis Tumoral alfa/farmacología , Vía de Señalización Wnt , beta Catenina/genética
4.
Open Med (Wars) ; 16(1): 1472-1481, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34703899

RESUMEN

Zinc finger nuclear transcription factor, X-box binding 1-type containing 1 antisense RNA 1 (ZFAS1) functions as an oncogenic long noncoding RNA (lncRNA) to promote proliferation and metastasis of endometrial carcinoma cell; however, the underlying mechanism has not been fully understood. First, RT-qPCR analysis of endometrial carcinoma tissues and cells showed that ZFAS1 was enriched in endometrial carcinoma tissues and cells. miR-34b was reduced in endometrial carcinoma and suggested negative correlation with ZFAS1 in endometrial carcinoma. Second, functional assays demonstrated that siRNA-mediated silence of ZFAS1 suppressed endometrial carcinoma cell proliferation and metastasis. Third, ZFAS1 bind to miR-34b and negatively regulate expression of miR-34b in endometrial carcinoma cells. miR-34b also bind to and negatively regulate expression of vascular endothelial growth factor A (VEGFA) in endometrial carcinoma cells. Lastly, knockdown of miR-34b counteracted with the suppressive effects of ZFAS1 silence on endometrial carcinoma cell proliferation and metastasis. In conclusion, lncRNA ZFAS1 functioned as an oncogene to promote endometrial carcinoma cell proliferation and metastasis through miR-34b/VEGFA axis.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1136-1140, 2021 Aug.
Artículo en Chino | MEDLINE | ID: mdl-34362493

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of CHOP regimen based on doxorubicin hydrochloride liposome in the initial treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Thirty-one patients with DLBCL treated from January 1, 2012 to December 31, 2019 were analyzed retrospectively, their median age was 83 (71-95) years old, and all of them were in Ⅲ-Ⅳ stage, including 17 cases who had international prognostic index (IPI) ≥ 3. The patients were treated with R-CHOP and CHOP regimens based on doxorubicin hydrochloride liposome. The efficacy and safety were evaluated during and after treatment. RESULTS: A total of 219 chemotherapy cycles and 7 median cycles were performed in 31 patients. The overall response (OR) rate and complete remission (CR) rate was 80.7% (25/31) and 61.3% (19/31), respectively, as well as 2 cases (6.5%) stable, 4 cases (12.9%) progressive. The main toxicities were as follows: the incidence of grade Ⅲ -Ⅳ neutropenia was 29% (9/31); two patients (6.5%) developed degree Ⅰ-Ⅱ cardiac events, which were characterized by new degree Ⅰ atrioventricular block; there were no cardiac events requiring emergency treatment and discontinuation of chemotherapy. The 1-year, 2-year and 3-year overall survival rate was 83.9%, 77.4% and 61.3%, respectively. The 1-year, 2-year and 3-year progression-free survival rate was 77.4%, 64.5% and 61.3%, respectively. CONCLUSION: The chemotherapy regimen based on doxorubicin hydrochloride liposome has better efficacy and higher cardiac safety for elderly patients with DLBCL.


Asunto(s)
Liposomas , Linfoma de Células B Grandes Difuso , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Liposomas/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisolona , Prednisona/uso terapéutico , Estudios Retrospectivos , Rituximab/uso terapéutico , Vincristina/uso terapéutico
6.
Front Genet ; 12: 610728, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34434212

RESUMEN

Background: Approximately 50% of cataracts are associated with genetic factors. Genetic etiology and molecular mechanisms based on gene research increase the understanding of cataracts and provide direction for diagnosis and intervention. In the present study, SCIE papers related to the modeling of cataract gene research from 2010-2019 were evaluated and qualitative and quantitative analyses with modeling performed. Methods: The SCIE database was searched on July 6, 2021 for cataract gene publications and relevant papers published since 2010 were considered for review. Subsequently, 1,904 SCIE papers associated with cataract genes from 2010-2019 were analyzed using a bibliometric method. The publication, country, institution, journal, references, knowledgebase, keywords, and research hotspots of the papers were analyzed using an online analysis platform of literature metrology, bibliographic item co-occurrence matrix builder (BICOMB), CiteSpace V, and VOS viewer analysis tool. Results: 78 countries published the related articles, and the United States ranks of America had the most publications. Two thousand seven hundred and eighty three institutions contributed to the related publications. Fudan University had the most publications. The reference clusters of SCI papers were clustered into six categories, namely, causing congenital cataract-microcornea syndrome, functional snp, cataractous lenses, a1 mutation, foxe3 mutation, cell adhesion gene pvrl3, nid1 gene. The key words representing the research frontiers were cerebrotendinous xanthomatosis (2017-2019), oxidative stress (2017-2019). Conclusion: This study provided a systematic, objective and comprehensive analysis of the literature related to gene research of cataract. Moreover, this study demonstrated the current hotspots and the future trends in the field of gene research of cataract. This review will help ophthalmologist to discern the dynamic evolution of cataract gene research, as well as highlight areas for future research.

7.
Nat Prod Res ; 35(17): 2849-2857, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31596143

RESUMEN

Two new highly-oxygenated neo-clerodane diterpenoids, 3S-acetoxyl-mollotucin D dilactone ester (1) and 6S-crotoeurin C (2), and a new lupane-type triterpene, 16ß-hydroxyl-3ß-O-trans-coumaroyl-betulin (6), as well as three known analogues (3-5) were obtained from the leaves of Croton laui. The structures of the new compounds were determined by extensive spectroscopic methods, and their absolute configurations were determined by combination of single-crystal X-ray diffraction analysis, electronic circular dichroism (ECD) spectra, and literature data. Compounds 2 and 3 exhibited inhibitory activities of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 values of 1.2 and 1.6 µM, respectively. Additionally, compound 6 exhibited activity against Col205 and HepG2 cell lines with IC50 values of 12.9 and 17.7 µM, respectively.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Croton , Diterpenos de Tipo Clerodano/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Dicroismo Circular , Croton/química , Diterpenos de Tipo Clerodano/aislamiento & purificación , Células Hep G2 , Humanos , Lipopolisacáridos , Ratones , Estructura Molecular , Óxido Nítrico , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Células RAW 264.7
8.
Oncol Rep ; 44(2): 577-588, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32627006

RESUMEN

Cancer stem cells are responsible for tumorigenesis, progression, recurrence and metastasis. Intestinal stem cells (ISCs) are regarded as the origin of intestinal neoplasia. Inflammation also serves an important role in intestinal neoplasia. To explore the molecular mechanisms underlying the inflammation­mediated induction of intestinal tumorigenesis, the present study investigated the function of tumor necrosis factor (TNF)­α in the malignant transformation of ISCs. NCM460 spheroid (NCM460s) cells with higher expression of stem cell genes, such as Oct4, Nanog, Sox2 and Lgr5, and with a higher ratio of CD133+, were obtained from NCM460 cells in serum­free medium. TNF­α accelerated cell proliferation, migration and invasion, induced chemotherapy resistance and the epithelial­mesenchymal transition. NF­κB and Wnt/ß­catenin pathways were activated in TNF­α­induced inflammatory responses, leading to the nuclear translocation of p65 and ß­catenin, as well as promoter activity of NF­κB and TCF/LEF transcription factors. It was further demonstrated that TNF­α­induced activation of the NF­κB and Wnt/ß­catenin signaling pathways, as well as the upregulation of proinflammatory cytokines, were significantly suppressed by p65­knockdown. Notably, PDTC, an inhibitor of NF­κB signaling, reversed TNF­α­induced activation of the NF­κB and Wnt/ß­catenin pathways. A similar role was observed for IWP­2, an inhibitor of Wnt/ß­catenin signaling. Collectively, these results demonstrated that the NF­κB and Wnt/ß­catenin pathways were activated to promote TNF­α­induced malignant transformation of ISCs, in which these two pathways cross­regulated each other.


Asunto(s)
Células Madre Adultas/patología , Antineoplásicos/farmacología , Transformación Celular Neoplásica/patología , Neoplasias Intestinales/patología , Factor de Necrosis Tumoral alfa/metabolismo , Antineoplásicos/uso terapéutico , Benzotiazoles/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica/efectos de los fármacos , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal/inmunología , Técnicas de Silenciamiento del Gen , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/patología , Neoplasias Intestinales/tratamiento farmacológico , Neoplasias Intestinales/inmunología , Prolina/análogos & derivados , Prolina/farmacología , Esferoides Celulares , Tiocarbamatos/farmacología , Factor de Transcripción ReIA/antagonistas & inhibidores , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Regulación hacia Arriba , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/inmunología
9.
Genomics ; 112(5): 3597-3608, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32320818

RESUMEN

OBJECTIVE: The objective was to find the role of long-non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1)/microRNA (miR)-129/high-mobility group box protein 1 (HMGB1) axis in polycystic ovary syndrome (PCOS). METHODS: Ovarian granulosa cells from non-PCOS patients and PCOS patients were collected, and HMGB1, miR-129 and lncRNA ZFAS1 expression were detected. Ovarian granulosa cells were transfected with si-ZFAS1 or miR-129 mimics to verify their roles in P4 and E2 secretion, and the biological functions of ovarian granulosa cells. RESULTS: LncRNA ZFAS1 and HMGB1 were elevated, while miR-129 was down-regulated in ovarian granulosa cells of PCOS patients. Down-regulated lncRNA ZFAS1 or overexpressed miR-129 could decrease HMGB1 expression, increase P4 and E2 secretion, promote proliferation activity while inhibit apoptosis of ovarian granulosa cells in PCOS. CONCLUSION: LncRNA ZFAS1 could bind to miR-129 to promote HMGB1 expression, thereby affecting the endocrine disturbance, proliferation and apoptosis of ovarian granulosa cells in PCOS.


Asunto(s)
Apoptosis/genética , Proliferación Celular/genética , Regulación hacia Abajo , Células de la Granulosa/patología , Proteína HMGB1/genética , MicroARNs/genética , Síndrome del Ovario Poliquístico/patología , ARN Largo no Codificante/genética , Regulación hacia Arriba , Progresión de la Enfermedad , Femenino , Humanos , Síndrome del Ovario Poliquístico/genética
10.
Biomed Res Int ; 2020: 8323658, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33426066

RESUMEN

OBJECTIVE: To study the efficacy of arthroscopy for treating symptomatic bone cysts of the foot and ankle through the follow-up of patients and to further explore the application value of 3D printing technology in this treatment. METHODS: Twenty-one patients with symptomatic bone cysts in the foot and ankle who underwent arthroscopic surgery in our Center from March 2010 to December 2018 were enrolled, including 11 in the experimental group and 10 in the control group. For the control group, C-arm fluoroscopy was used intraoperatively to confirm the positioning of the cysts; for the experimental group, a 3D model of the lesion tissue and the 3D-printed individualized guides were prepared to assist the positioning of the cysts. Debridement of the lesion tissues was conducted under an arthroscope. Regular follow-ups were conducted. The time of establishing arthroscopic approaches and the times of intraoperative fluoroscopy between the two groups were compared. Significance was determined as P < 0.05. RESULTS: The postoperative pathology of the patients confirmed the diagnosis. No significant perioperative complications were observed in either group, and no recurrence of bone cysts was seen at the last follow-up. The VAS scores and AOFAS scores of the two groups at the last follow-up were significantly improved compared with the preoperative data, but there was no statistical difference between the two groups. All surgeries were performed by the same senior surgeon. The time taken to establish the arthroscopic approaches between the two groups was statistically significant (P < 0.001), and the times of intraoperative fluoroscopy required to establish the approach were also statistically significant (P < 0.001). The intraoperative bleeding between the two groups was statistically significant (P < 0.01). There was 1 case in each group whose postoperative CT showed insufficient bone grafting, but no increase in cavity volume was observed during the follow-up. CONCLUSION: With the assistance of the 3D printing technology for treating symptomatic bone cysts of the ankle and foot, the surgeon can design the operation preoperatively and perform the rehearsal, which would make it easier to establish the arthroscopic approach, better understand the anatomy, and make the operation smoother. This trial is registered with http://www.clinicaltrials.govNCT03152916.


Asunto(s)
Articulación del Tobillo , Artroscopía/métodos , Quistes Óseos , Impresión Tridimensional , Adulto , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/cirugía , Artroscopía/efectos adversos , Quistes Óseos/diagnóstico por imagen , Quistes Óseos/cirugía , Femenino , Fluoroscopía , Estudios de Seguimiento , Huesos del Pie/diagnóstico por imagen , Huesos del Pie/cirugía , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias
11.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3429-3434, 2019 Aug.
Artículo en Chino | MEDLINE | ID: mdl-31602905

RESUMEN

The aim of this paper was to observe the concentration,time and mechanism of autophagy induced by triptolide( TP) in ovarian granulosa cells( OGCs). CCK-8 method was used to compare the inhibitory effects of TP at different concentrations on primary cultured rat OGCs and IC50 was calculated. The effects of TP at different concentrations and time points on the expression of OGCs autophagy factor protein and the cascade of PI3 K/AKT/m TOR pathway were detected by Western blot. The effects of TP,autophagy inducer( brefeldin A) and PI3 K/m TOR inhibitor( NVP-BEZ235) on the expression of PI3 K/AKT/m TOR cascade and autophagy related factor protein were detected by Western blot. The results show that the IC50 of different concentrations of TP on OGCs of rat ovary was14. 65 µmol·L-1,and the minimum inhibitory concentration of TP was 0. 1 µmol·L-1( 100 nmol·L-1). Compared with the control group,the expression levels of beclin1 and LC3Ⅱ in each group were significantly higher than those in the control group( P<0. 05 or P<0. 01). After 12 hours of treatment with TP,brefeldin A and NVP-BEZ235,respectively,compared with the control group,TP could significantly promote the expression level of downstream autophagy effect or molecule beclin1,LC3Ⅱ and inhibit the expression level of LC3Ⅰ,p62 protein( P<0. 05 or P< 0. 01). Moreover,the expression of beclin1 and LC3Ⅱ/LC3Ⅰ in TP group was higher than that in brefeldin A group( P<0. 05 or P<0. 01),and the expression of p62 in TP group was lower than that in brefeldin A group( P<0. 05 or P<0. 01). At the same time,TP could significantly inhibit the expression of p-PI3 K,p-AKT,p-mTOR protein,and the inhibitory effect of TP was better than that of NVP-BEZ235 group. This study suggests that 100 nmol·L-1 TP could induce OGCs autophagy successfully in cultured rat ovary for 12 h; TP may induce OGCs autophagy by inhibiting PI3 k/Akt/m TOR signaling pathway.


Asunto(s)
Autofagia , Diterpenos/farmacología , Células de la Granulosa/efectos de los fármacos , Fenantrenos/farmacología , Transducción de Señal , Animales , Apoptosis , Proliferación Celular , Células Cultivadas , Compuestos Epoxi/farmacología , Femenino , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Serina-Treonina Quinasas TOR/metabolismo
12.
Artif Cells Nanomed Biotechnol ; 47(1): 1248-1255, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30945565

RESUMEN

Mitochondrial dysfunction is a major contributory factor for myocardial ischemia-reperfusion (I/R) injury. It has been reported that Pink1-Parkin-mediated mitochondrial autophagy could effectively remove damaged mitochondria and excess ROS to ensure the stability of intracellular mitochondria. The present study was designed to evaluate whether the polymerized porcine haemoglobin (pPolyHb), a novel type of haemoglobin oxygen carrier, has an effect on I/R injury via regulating the Pink1-Parkin mediated mitochondrial autophagy pathway in myocardial H9C2 cells. The results revealed that pPolyHb could effectively reduce apoptosis and improve the survival rates of H9C2 cells. In addition, Pink1 and Parkin levels gradually decreased with pPolyHb reoxygenation. The inhibition of mitochondrial autophagy through mitochondrial-division inhibitor-1(mdivi-1) resulted in a decrease in anti-apoptotic protein Bcl-2 and an increase in pro-apoptotic protein Bax and CytC. In conclusion, pPolyHb has a protective effect on myocardial ischemia-reperfusion injury by regulating moderate mitochondrial autophagy.


Asunto(s)
Autofagia/efectos de los fármacos , Hemoglobinas/farmacología , Mitocondrias/efectos de los fármacos , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/efectos de los fármacos , Proteínas Quinasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocromos c/metabolismo , Citoprotección/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Hemoglobinas/química , Humanos , L-Lactato Deshidrogenasa/metabolismo , Mitocondrias/patología , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Oxígeno/metabolismo , Multimerización de Proteína , Estructura Cuaternaria de Proteína , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Porcinos , Proteína X Asociada a bcl-2/metabolismo
13.
Mol Genet Genomic Med ; 7(6): e667, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30941921

RESUMEN

BACKGROUND: Colorectal cancer is the third most common cancer worldwide. Recently, an increasing number of evidences suggest that genetic susceptibility plays an important role in the occurrence of colorectal cancer. This study aimed to better understand the influence of MIR17HG polymorphisms on colorectal cancer susceptibility in the Chinese Han population. METHODS: We recruited 514 patients with colorectal cancer and 510 healthy controls to investigate the association between polymorphisms of MIR17HG and risk of colorectal cancer in the Chinese Han population. Genotyping was performed with the Agena MassARRAY platform. We used the χ2 test to compare the distributions of single nucleotide polymorphisms (SNPs) allele and genotypes frequencies between cases and controls. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis to evaluate the association under genetic models. Linkage disequilibrium between the five SNPs was assessed using the Haploview software. RESULTS: Overall analysis found that rs7336610 and rs1428 and haplotype CTAGA were significantly associated with increased risk of colorectal cancer. However, we found rs7318578 was associated with a decreased risk of colorectal cancer in the dominant model. Stratification analysis showed that rs7336610, rs7318578, and rs1428 were also associated with rectal cancer risk. Gender stratification analysis found that rs7336610, rs7318578, rs17735387, and rs1428 were significantly associated with colorectal cancer risk in males. CONCLUSION: In conclusion, this study indicated that the polymorphisms of MIR17HG were associated with colorectal cancer risk. Therefore, our findings may provide new insights into the development of colorectal cancer. Further association and functional studies are of great importance to confirm these results and to define the potential biological mechanism of colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/genética , MicroARNs/genética , Anciano , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Neoplasias del Colon/genética , Etnicidad/genética , Femenino , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento/genética , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Nucleótido Simple/genética , ARN Largo no Codificante , Factores de Riesgo
14.
Artif Cells Nanomed Biotechnol ; 47(1): 1101-1112, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30942098

RESUMEN

Cases of more than three primary cancers are very rare. This study analyzed the genetic susceptibility of gene polymorphisms in three patients with multiple primary malignant neoplasms and examined the possible pathogenesis. The clinical data and whole genome sequence of three patients (1 with 5 primary cancers, 1 with 4 primary cancers, and 1 with 3 primary cancers) were aligned with a series of databases. We found the three patients contained a total of seven types of malignant tumours (endometrial cancer, ovarian cancer, breast cancer, colon cancer, ureter cancer, bladder cancer and kidney cancer). It was found that the varied genes in Patient 1 (5 primary cancers) were BRIP1, FANCG, NBN, AXIN2, SRD5A2, and CEBPA. Patient 2 (4 primary cancers) had variations in the following genes: BMPR1A, FANCD2, MLH3, BRCA2, and FANCM. Patient 3 (3 primary cancers) had variations in the following genes: MEN1, ATM, MSH3, BRCA1, FANCL, CEBPA, and FANCA. String software was used to analyze the KEGG pathway of the variations in these three samples, which revealed that the genes are involved in the Fanconi anaemia pathway. Defects in DNA damage repair may be one of the causes of multiple primary cancers.


Asunto(s)
Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Neoplasias Primarias Múltiples/genética , Polimorfismo Genético , Anciano , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/metabolismo , Programas Informáticos
15.
Artículo en Inglés | MEDLINE | ID: mdl-30402135

RESUMEN

Background. The formulation of Bu Shen Yang Xue (BSYX) has been clinically used in treating gynecologic disease in China, especially for the development of the endometrium. Endometrial carcinoma is the most common malignant tumor of the female genital tract in developed countries. And few studies have been reported on the antitumor activity of BSYX. Therefore, this study aimed to investigate the effect of BSYX on endometrial cancer and make an initial discussion of the underlining mechanisms in Ishikawa cells. Methods and Results. Firstly, 60 SPF female nude mice were randomly divided into control group, model group, BSYX group, and positive group. The models of subcutaneous tumor xenograft of nude mice were established by injection of human endometrial carcinoma cell line Ishikawa tumor cell suspension. Compared with model group, BSYX reduced effectively tumor volume and changed pathological feature in mice tumor issue. Meanwhile, proteins from tumor issues were detected by western blot analysis. The protein levels of follicle-stimulating hormone receptor (FSHR), p-Akt/Akt, Gankyrin, and cyclinD1 in the model group were higher than those in control group but the expression in BSYX group was lower than that in the model group. The hypoxia inducible factor alpha (HIF-α) protein level in the model group was lower than those in control group and upregulated in BSYX group. In addition, Ishikawa cells were cultured and then exposed to follicle-stimulating hormone (FSH), LY294002, a highly selective PI3K inhibitor and serum containing BSYX, respectively. LY294002 and BSYX markedly decreased the cancer cell viability and migration ability and increased the apoptosis rate. FSH promoted the cancer cell ability and migration ability. LY294002 and BSYX evidently downregulated the proteins levels of FSHR, p-Akt/Akt, Gankyrin, and cyclinD1 and upregulated the expression of HIF-α protein, and FSH was on the opposite. Conclusions. Taken together, our results showed that the formulation of BSYX had antitumor effect on endometrial cancer in vivo and in vitro and was related with FSH/PI3K/AKT/Gankyrin/HIF-α/cyclinD1 transduction pathway.

16.
Nanoscale ; 10(24): 11384-11391, 2018 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-29877544

RESUMEN

Micromotors hold promise as drug carriers for targeted drug delivery owing to the characteristics of self-propulsion and directional navigation. However, several defects still exist, including high cost, short movement life, low drug loading and slow release rate. Herein, a novel catalytic micromotor based on porous zeolitic imidazolate framework-67 (ZIF-67) synthesized by a greatly simplified wet chemical method assisted with ultrasonication is described as an efficient anticancer drug carrier. These porous micromotors display effective autonomous motion in hydrogen peroxide and long durable movement life of up to 90 min. Moreover, the multifunctional micromotor ZIF-67/Fe3O4/DOX exhibits excellent performance in precise drug delivery under external magnetic field with high drug loading capacity of fluorescent anticancer drug DOX up to 682 µg mg-1 owing to its porous nature, high surface area and rapid drug release based on dual stimulus of catalytic reaction and solvent effects. Therefore, these porous ZIF-67-based catalytic micromotors combine the domains of metal-organic frameworks (MOFs) and micomotors, thus developing potential resources for micromotors and holding great potential as label-free and precisely controlled high-quality candidates of drug delivery systems for biomedical applications.


Asunto(s)
Portadores de Fármacos/química , Estructuras Metalorgánicas/química , Zeolitas/química , Antibióticos Antineoplásicos/administración & dosificación , Catálisis , Doxorrubicina/administración & dosificación , Liberación de Fármacos , Compuestos Férricos , Porosidad , Ultrasonido
17.
Int J Hematol ; 107(6): 666-672, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29488168

RESUMEN

The objective of the study was to study the regulation of B lymphocytes in patients with autoimmune hemolytic anemia (AIHA)/Evans syndrome. From October 2015 to May 2016, 35 patients with AIHA/Evans in the Department of Hematology, Tianjin Medical University General Hospital were enrolled into this study. c-Myb mRNA and miR-150 expression in B lymphocytes were measured using real-time PCR (RT-PCR). Correlation between c-Myb and miR-150 and clinical parameters in patients with AIHA/Evans were analyzed. c-Myb mRNA expression in hemolysis patients was significantly higher than in remission patients and CLL patients, negatively correlated with hemoglobin (Hb) level and complement 3(C3) levels, and positively correlated with total bilirubin (TBIL) concentration and indirect bilirubin (IBIL) concentration. miR-150 expression in hemolysis patients was significantly lower than in patients in remission and CLL patients. miR-150 was negatively correlated with TBIL and IBIL, and positively correlated with Hb, C3. c-Myb mRNA expression levels in hemolytic episode patients were negatively correlated with the expression levels of miR-150. The expression of c-Myb, a regulatory factor of B lymphocytes, is increased in B lymphocytes of AIHA/Evans patients, while miR-150 expression is decreased. c-Myb was negatively correlated with miR-150.


Asunto(s)
Anemia Hemolítica Autoinmune/inmunología , Linfocitos B/inmunología , MicroARNs/fisiología , Proteínas Proto-Oncogénicas c-myb , Trombocitopenia/inmunología , Adolescente , Adulto , Anciano , Anemia Hemolítica Autoinmune/sangre , Bilirrubina/sangre , Complemento C3/metabolismo , Femenino , Expresión Génica , Hemoglobinas , Hemólisis , Humanos , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-myb/genética , Proteínas Proto-Oncogénicas c-myb/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto Joven
19.
Nano Lett ; 17(12): 7897-7907, 2017 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-29161046

RESUMEN

A novel renewable cathode made from earth abundant, low-cost materials can contribute to the intermittent storage needs of renewable energy-based society. In this work, we report for the first-time tannin from Nature as a cathode material. Our approach exploits the charge storage mechanism of the redox active quinone moiety. Tannins extracted from tree bark using environmental friendly aqueous solvents have the highest phenol content (5.56 mol g-1) among all the natural phenolic biopolymers, 5000 times higher than lignin. Tannins coupled with a conductive polymer polypyrrole acquire high specific capacitance values of 370 F g-1 at 0.5 A g-1 as well as excellent rate performance of 196 F g-1 at 25 A g-1. Additionally, we employed carbonized wood as an electrode substrate to produce a sustainable electrochemical device with dramatically improved performance compared to conventional devices. The high surface area provided by the well-aligned, cellular porosity of wood-derived substrate combined with the high mobility of ions and electrons in the carbonized cell walls and deposited tannin can achieve an areal capacitance of 4.6 F cm-2 at 1 mA cm-2, which is 1.5 times higher than activated wood carbon.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(1): 120-125, 2017 Feb.
Artículo en Chino | MEDLINE | ID: mdl-28245387

RESUMEN

OBJECTIVE: To analyze the clinical features and treatment methods of refractory/relapsed diffuse large B cell lymphoma (DLBCL) patients, and to explore the curative effect and the main factors affecting prognosis. METHODS: Clinical data of 1043 cases of DLBCL in our hospital from January 2008 to April 2016 were retrospectively analyzed, then the clinical data of 153 patients with refractory/relapsed lymphoma were selected and analyzed for determing the relationship of the related factors with therapeutic effect and prognosis. Treatment methods include chemotherapy alone and chemotherapy combined with radio-therapy, the first line regimen was CHOP or R-CHOP program, the salvage regimens are ICE, Hyper CVAD or EPOCH, etc. The median age of these 153 patients was 50 years old, the ratio of male and female was 1.59:1. RESULTS: 4 cases were not treated in 153 patients, 6 cases (4.03%) of 149 patients have been treated and achieved complete remission(CR), 18 cases (12.08%) achieved partial remission(PR), and the total response rate was 16.1%. Single factor analysis showed that the patients' serum LDH values, IPI score, bulky, extra-node involvement, bone marrow infiltration and the salvage regimen all could influence the survival rate, with statistically significantce (P<0.05). CONCLUSION: Refractory/relapsed DLBCL mainly occurs in the middle-aged and male, the serum LDH value, IPI score, bulky and scope of lesions are mainly factors influencing the prognosis of refractory/relapsed DLBCL patients.


Asunto(s)
Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Terapia Recuperativa , Resultado del Tratamiento
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