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1.
J Cell Mol Med ; 28(15): e18549, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39098994

RESUMO

Breast cancer (BC) is the most commonly diagnosed cancer in women globally. Natural killer (NK) cells play a vital role in tumour immunosurveillance. This study aimed to establish a prognostic model using NK cell-related genes (NKRGs) by integrating single-cell transcriptomic data with machine learning. We identified 44 significantly expressed NKRGs involved in cytokine and T cell-related functions. Using 101 machine learning algorithms, the Lasso + RSF model showed the highest predictive accuracy with nine key NKRGs. We explored cell-to-cell communication using CellChat, assessed immune-related pathways and tumour microenvironment with gene set variation analysis and ssGSEA, and observed immune components by HE staining. Additionally, drug activity predictions identified potential therapies, and gene expression validation through immunohistochemistry and RNA-seq confirmed the clinical applicability of NKRGs. The nomogram showed high concordance between predicted and actual survival, linking higher tumour purity and risk scores to a reduced immune score. This NKRG-based model offers a novel approach for risk assessment and personalized treatment in BC, enhancing the potential of precision medicine.


Assuntos
Neoplasias da Mama , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células Matadoras Naturais , Aprendizado de Máquina , Análise de Célula Única , Transcriptoma , Microambiente Tumoral , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Feminino , Prognóstico , Transcriptoma/genética , Análise de Célula Única/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Nomogramas
2.
J Cell Physiol ; 234(7): 11692-11707, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30515795

RESUMO

Existing evidence has highlighted the effect of ultraviolet light radiation leading to corneal epithelium impairment. During this study, we aim to investigate the effect of microRNA-129-5p (miR-129-5p) on the wound healing process of corneal epithelial cells (CECs) induced by ultraviolet rays in mice by targeting epidermal growth factor receptor (EGFR). First, mouse models of ultraviolet ray-induced CEC injury were established and intrastromally injected with different mimic, inhibitor, and short interfering RNA (siRNA) to detect the effect of miR-129-5p on CEC injury. Subsequently, the corneal tissues were obtained to detect the antioxidant ability and EGFR-positive expression rate. The dual-luciferase reporter gene assay was used to test whether EGFR could directly target miR-129-5p. To further investigate the specific mechanism of miR-129-5p and EGFR in CEC injury, CECs were cultured and transfected with miR-129-5p mimic, miR-129-5p inhibitor, siRNA-EGFR, and miR-129-5p inhibitor + siRNA-EGFR. miR-129-5p has been proven to directly target EGFR. Inhibition of miR-129-5p is able to increase the antioxidant capacity, EGFR-positive rate and the expressions of EGFR, B-cell lymphoma-2, zonula occluden-1, occludin, and keratinocyte growth factor-2, but decrease the expression of vascular endothelial growth factor, BCL2-associated X protein, interleukin (IL)-1ß, and IL-4. Inhibition of miR-129-5p arrests cells at the S and G2 phases and decreases apoptosis. Our study provides evidence stating that inhibiting miR-129-5p and upregulating EGFR could aid in the repair of mice CEC injury induced by ultraviolet radiation. Therefore, inhibition of miR-129-5p might provide a basic theory in the repair of CEC injury caused by ultraviolet rays.


Assuntos
Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Epitélio Corneano/lesões , Receptores ErbB/genética , MicroRNAs/metabolismo , Raios Ultravioleta , Regulação para Cima/genética , Animais , Antioxidantes/metabolismo , Apoptose/genética , Apoptose/efeitos da radiação , Sequência de Bases , Colágeno/metabolismo , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Epitélio Corneano/patologia , Epitélio Corneano/efeitos da radiação , Epitélio Corneano/ultraestrutura , Receptores ErbB/metabolismo , Fase G1/genética , Fase G1/efeitos da radiação , Luciferases/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Neovascularização Patológica/genética , Ocludina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxido Dismutase/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/efeitos da radiação , Regulação para Cima/efeitos da radiação , Proteína da Zônula de Oclusão-1/metabolismo
3.
Exp Cell Res ; 346(2): 147-56, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27364911

RESUMO

Cerebrovascular aging has a high relationship with stroke and neurodegenerative disease. In the present study, we evaluated the influence of fibroblast growth factor 21 (FGF21) on angiotensin (Ang II)-mediated cerebrovascular aging in human brain vascular smooth muscle cells (hBVSMCs). Ang II induced remarkable aging-phenotypes in hBVSMCs, including enhanced SA-ß-gal staining and NBS1 protein expression. First, we used immunoblotting assay to confirm protein expression of FGF21 receptor (FGFR1) and the co-receptor ß-Klotho in cultured hBVSMCs. Second, we found that FGF21 treatment partly prevented the aging-related changes induced by Ang II. FGF21 inhibited Ang II-enhanced ROS production/superoxide anion levels, rescued the Ang II-reduced Complex IV and citrate synthase activities, and suppressed the Ang II-induced meprin protein expression. Third, we showed that FGF21 not only inhibited the Ang II-induced p53 activation, but also blocked the action of Ang II on Siah-1-TRF signaling pathway which is upstream factors for p53 activation. At last, either chemical inhibition of AMPK signaling pathway by a specific antagonist Compound C or knockdown of AMPKα1/2 isoform using siRNA, successfully abolished the anti-aging action of FGF21 in hBVSMCs. These results indicate that FGF21 protects against Ang II-induced cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 activation in an AMPK-dependent manner, and highlight the therapeutic value of FGF21 in cerebrovascular aging-related diseases such as stroke and neurodegenerative disease.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Encéfalo/irrigação sanguínea , Senescência Celular/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/farmacologia , Biogênese de Organelas , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Angiotensina II/farmacologia , Encéfalo/efeitos dos fármacos , Colágeno/genética , Colágeno/metabolismo , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Proteínas Nucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteína 2 de Ligação a Repetições Teloméricas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
4.
Zhonghua Zhong Liu Za Zhi ; 35(9): 703-7, 2013 Sep.
Artigo em Zh | MEDLINE | ID: mdl-24332060

RESUMO

OBJECTIVE: To assess the accuracy of detection by automated breast volume scanner (ABVS) in diagnosis of high-risk and small breast lesions. METHODS: One hundred and twelve patients with solid high-risk and small breast lesions were identified by ABVS. The patients were divided into benign lesion group and cancer group after pathological examination. The clinicopathological findings and ultrasonographic features of the lesions were compared. RESULTS: Among the 112 lesions there were 49 benign and 63 malignant lesions. The mean size on ABVS and pathology were (1.59 ± 0.52) cm and (1.52 ± 0.58) cm. There was no significant difference in tumor sizes determined by ABVS and pathology (P = 0.194). The mean age of patients with benign lesions was (38.5 ± 7.4) years and that of malignant lesions was (52.4 ± 13.6) years, showing a significant difference between the two groups (P < 0.001) . The mass shape, orientation, margin, lesion boundary, echo pattern, calcification, BI-RADS category and retraction phenomenon were significantly different of the malignant and benign masses (P < 0.05). But there was no significant difference in the location of lesions and posterior acoustic features (P > 0.05) . Retraction phenomenon was significantly associated with pathological type and histologic grade of the breast cancer (P < 0.01). The specificity, sensitivity and accuracy of retraction phenomenon were 100% (46/46), 73.0% (46/63), and 84.8% (95/112), respectively. CONCLUSIONS: ABVS provides advantages of better size prediction of high-risk and small breast lesions. Furthermore, the retraction phenomenon in coronal plane shows high specificity and sensitivity in detecting breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Fibroadenoma/diagnóstico por imagem , Ultrassonografia Mamária/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Fibroadenoma/patologia , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Carga Tumoral , Adulto Jovem
5.
Zhong Xi Yi Jie He Xue Bao ; 8(9): 877-82, 2010 Sep.
Artigo em Zh | MEDLINE | ID: mdl-20836979

RESUMO

OBJECTIVE: To explore the effects of different proportions of Fructus Cnidii (Shechuangzi) and Psoralea corylifolia (Buguzhi) on highly metastatic human breast cancer cell line MDA-MB-231BO and bone marrow stromal cell line ST-2 in vitro. METHODS: Thirty-six female SD rats were randomly divided into 6 groups to prepare the drug-medicated sera by administering with different proportions of Fructus Cnidii and Psoralea corylifolia, including 4:0 group, 3:1 group, 1:1 group, 1:3 group, 0:4 group and control group. MDA-MB-231BO cells and ST-2 cells were cultured in Dulbecco's modified Eagle's medium containing drug-medicated serum. Inhibition rates of MDA-MB-231BO cells and ST-2 cells were measured by methyl thiazolyl tetrazolium (MTT) method; migration ability of MDA-MB-231BO cells was tested by a cell migration experiment; alkaline phosphatase activity (ALP) of ST-2 cells was measured by using 4-nitrophenyl phosphate disodium salt, and mineralized nodule formation of ST-2 cells was measured by alizarin red staining. RESULTS: Sera contaning different proportions of Fructus Cnidii and Psoralea corylifolia inhibited the migration activity of MDA-MB-231BO cells as compared with the blank serum, and serum contaning Fructus Cnidii and Psoralea Corylifolia at proportion of 1:1 had the best function (P<0.01). Fructus Cnidii and Psoralea corylifolia at ratio of 1:1 also enhanced the ALP activity of ST2 cells (P<0.05) and increased the number of mineralized nodules of ST2 cells (P<0.01). CONCLUSION: Kidney-warming recipe of Fructus Cnidii and Psoralea corylifolia can inhibit proliferation and migration of MDA-MB-231BO cells and increase the activity of ST-2 cells.


Assuntos
Neoplasias da Mama/patologia , Frutas , Extratos Vegetais/farmacologia , Psoralea , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Células-Tronco Mesenquimais , Metástase Neoplásica , Ratos , Ratos Sprague-Dawley
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