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The current study was aimed at the assessment of the effect of chitosan-ZnO/Selenium nanoparticles scaffold on infected wound healing and care of paediatric surgery treatment. The nanoparticle scaffolds were developed from sources such as chitosan (CS), different concentrations of zinc oxide (ZnO), and Selenium (SeNPs) nanoparticles by freeze-drying method. The structural and chemical properties of nanoparticles were investigated by UV-Vis, fourier transform infrared spectroscopy (FTIR), and phase identification by x-ray diffraction analysis. The surface morphology of CS, chitosan-ZnO (CS-ZnO) and chitosan-ZnO/SeNPs was analysed using a scanning electron microscope. The incorporation of ZnO and SeNPs along with CS polymer induces antioxidant and antimicrobial functions. The bacterial susceptibility to nanoparticle scaffolds against Escherichia coli and Staphylococcus aureus showed the excellent antibacterial effects of ZnO and SeNPs. In-vitro studies of fibroblast of NIH 3 T3 and HaCaT cell lines revealed the biocompatibility, cell adhesion, cell viability, and proliferation of scaffold in the wound site. Also, results of in-vivo studies strongly enhanced collagen synthesis, re-epithelialization, and rapid wound closure. Thus, the synthesised chitosan-ZnO/SeNPs nanoparticle scaffold resulted in significant improvement in histopathological indices in the full thickness of wound healing after nursing care of paediatric fracture surgery.
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Quitosano , Nanopartículas , Atención de Enfermería , Selenio , Óxido de Zinc , Humanos , Niño , Óxido de Zinc/uso terapéutico , Óxido de Zinc/química , Óxido de Zinc/farmacología , Quitosano/uso terapéutico , Selenio/uso terapéutico , Selenio/química , Selenio/farmacología , Nanopartículas/uso terapéutico , Nanopartículas/química , Cicatrización de Heridas , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Bacterias , VendajesRESUMEN
BACKGROUND: Ewing sarcoma, the second most frequent bone tumor in children and adolescents, is often presented with localized disease or metastatic-related symptoms. In this study, we aim to construct and validate a nomogram for patients with Ewing sarcoma to predict the 3- and 5-year overall survival (OS) based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Demographic and clinic pathological characteristics of patients with Ewing sarcoma diagnosed between 2010 and 2015 were extracted from SEER database. Univariate and multivariate Cox analyses were carried out to identify the independent characteristics. The independent factors were further included into the construction of a nomogram. Finally, c-index and calibration curves were used to validate the nomogram. RESULTS: A total of 578 patients were enrolled into our analysis. The results of univariate Cox analysis showed that age, 7th AJCC stage, 7th AJCC T stage, 7th AJCC N stage, 7th AJCC M stage, metastatic status to lung, liver and bone were significant factors. Multivariate Cox analysis was performed and it confirmed age, N stage and bone metastasis as independent variables. Next, a nomogram was constructed using these independent variables in prediction to the 3- and 5-year OS. Furthermore, favorable results with c-indexes (0.757 in training set and 0.697 in validation set) and calibration curves closer to ideal curves indicated the accurate predictive ability of this nomogram. CONCLUSIONS: The individualized nomogram demonstrated a good ability in prognostic prediction for patients with Ewing sarcoma.
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Nomogramas , Sarcoma de Ewing , Adolescente , Niño , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Pronóstico , Programa de VERF , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/epidemiologíaRESUMEN
The S100 protein family represents the largest subgroup of calcium binding EF-hand type proteins. These proteins have been reported to be involved in a wide range of biological functions that are related to normal cell development and tumorigenesis. S100A14 is a recently identified member of the S100 protein family and differentially expressed in a number of different human malignancies. However, the transcriptional regulation of S100A14 and its role in breast cancer needs to be further investigated. Here, we determined that 12-O-tetradecanoylphorbol-13-acetate (TPA) up-regulated the expression of KLF4 and facilitated its binding directly to two conserved GC-rich DNA segments within the S100A14 promoter, which is essential for the transactivation of KLF4 induced S100A14 expression. Furthermore, stable silencing of KLF4 significantly suppressed breast cancer cell migration induced by TPA. Collectively, these results offer insights into the fact that TPA provokes cell motility through regulating the expression and function of S100A14 in a KLF4-dependent manner.
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Neoplasias de la Mama/patología , Proteínas de Unión al Calcio/metabolismo , Movimiento Celular/efectos de los fármacos , Factores de Transcripción de Tipo Kruppel/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Animales , Secuencia de Bases , Sitios de Unión , Proteínas de Unión al Calcio/deficiencia , Proteínas de Unión al Calcio/genética , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen , Humanos , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/deficiencia , Factores de Transcripción de Tipo Kruppel/genética , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de TiempoRESUMEN
OBJECTIVE: This study aimed to detect the genotype distributions and allele frequencies of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms of pregnant women in Jiaodong region in China, and to investigate whether folic acid supplementation affect the pregnancy complications. SETTING: A total of 7,812 pregnant women from the Jiaodong region in Shandong province in China. METHODS: By using Taqman-MGB, 2,928 pregnant women (case group) were tested for the genotype distributions and allele frequencies of MTHFR C677T, A1298C and MTRR A66G polymorphisms. Folic acid metabolism ability was ranked at four levels and then pregnant women in different rank group were supplemented with different doses of folic acid. Their pregnancy complications were followed up and compared with 4,884 pregnant women without folic acid supplementation (control group) in the same hospital. RESULTS: The allele frequencies of MTHFR C677T were 49.1 and 50.9%; those of MTHFR A1298C were 80.2 and 19.8%, and those of MTRR A66G were 74.1 and 25.9%. After supplemented with folic acid, the complication rates in different age groups were significantly reduced, especially for gestational diabetes mellitus and hypertension. CONCLUSION: Periconceptional folic acid supplementation and healthcare following gene polymorphism testing may be a powerful measure to decrease congenital malformations.
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Ferredoxina-NADP Reductasa/genética , Ácido Fólico/farmacología , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Complicaciones del Embarazo/prevención & control , Complejo Vitamínico B/farmacología , Adulto , China/epidemiología , Femenino , Ácido Fólico/administración & dosificación , Frecuencia de los Genes , Humanos , Polimorfismo Genético , Embarazo , Complicaciones del Embarazo/epidemiología , Resultado del Tratamiento , Complejo Vitamínico B/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) is treated with transurethral resection of bladder tumor (TURBT) followed by intravesical instillation of chemotherapy or Bacillus Calmette-Guérin therapy. However, these treatments have a high recurrence rate and side effects, emphasizing the need for alternative instillations. Previously, we revealed that expanded allogeneic human natural killer (NK) cells from peripheral blood are a promising cellular therapy for prostate cancer. However, whether NK cells exhibit a similar killing effect in bladder cancer (BCa) remains unknown. METHODS: Expansion, activation, and cryopreservation of allogeneic human NK cells obtained from peripheral blood were performed as we previously described. In vitro cytotoxicity was evaluated using the cell counting kit-8. The levels of perforin, granzyme B, interferon-γ, tumor necrosis factor-α, and chemokines (C-C-motif ligand [CCL]1, CCL2, CCL20, CCL3L1, and CCL4; C-X-C-motif ligand [CXCL]1, CXCL16, CXCL2, CXCL3, and CXCL8; and X-motif ligand 1 and 2) were determined using enzyme-linked immunosorbent assay. The expression of CD107a, major histocompatibility complex class I (MHC-I), MHC-I polypeptide-related sequences A and B (MICA/B), cytomegalovirus UL16-binding protein-2/5/6 (ULBP-2/5/6), B7-H6, CD56, CD69, CD25, killer cell Ig-like receptors (KIR)2DL1, KIRD3DL1, NKG2D, NKp30, NKp46, and CD16 of NK cells or BCa and normal urothelial cells were detected using flow cytometry. Cytotoxicity was evaluated using lactate dehydrogenase assay in patient-derived organoid models. BCa growth was monitored in vivo using calipers in male NOD-scid IL2rg-/- mice subcutaneously injected with 5637 and NK cells. Differential gene expressions were investigated using RNA sequence analysis. The chemotaxis of T cells was evaluated using transwell migration assays. RESULTS: We revealed that the NK cells possess higher cytotoxicity against BCa lines with more production of cytokines than normal urothelial cells counterparts in vitro, demonstrated by upregulation of degranulation marker CD107a and increased interferon-γ secretion, by MICA/B/NKG2D and B7H6/NKp30-mediated activation. Furthermore, NK cells demonstrated antitumor effects against BCa in patient-derived organoids and BCa xenograft mouse models. NK cells secreted chemokines, including CCL1/2/20, to induce T-cell chemotaxis when encountering BCa cells. CONCLUSIONS: The expanded NK cells exhibit potent cytotoxicity against BCa cells, with few toxic side effects on normal urothelial cells. In addition, NK cells recruit T cells by secreting a panel of chemokines, which supports the translational application of NK cell intravesical instillation after TURBT from bench to bedside for NMIBC treatment.
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Trasplante de Células Madre Hematopoyéticas , Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Animales , Ratones , Citotoxicidad Inmunológica , Interferón gamma/metabolismo , Ligandos , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Resección Transuretral de la Vejiga , Línea Celular Tumoral , Ratones Endogámicos NOD , Células Asesinas Naturales/metabolismo , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/metabolismo , Receptores de Células Asesinas Naturales/metabolismo , QuimiocinasRESUMEN
BACKGROUND: Compared with intravascular ultrasound guidance, there is limited evidence for optical coherence tomography (OCT) guidance during primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients. AIMS: We investigated the role of OCT in guiding a reperfusion strategy and improving the long-term prognosis of STEMI patients. METHODS: All patients who were diagnosed with STEMI and who underwent pPCI between January 2017 and December 2020 were enrolled and divided into OCT-guided versus angiography-guided cohorts. They had routine follow-up for up to 5 years or until the time of the last known contact. All-cause death and cardiovascular death were designated as the primary and secondary endpoints, respectively. RESULTS: A total of 3,897 patients were enrolled: 2,696 (69.2%) with OCT guidance and 1,201 (30.8%) with angiographic guidance. Patients in the OCT-guided cohort were less often treated with stenting during pPCI (62.6% vs 80.2%; p<0.001). The 5-year cumulative rates of all-cause mortality and cardiovascular mortality in the OCT-guided cohort were 10.4% and 8.0%, respectively, significantly lower than in the angiography-guided cohort (19.0% and 14.1%; both log-rank p<0.001). All 4 multivariate models showed that OCT guidance could significantly reduce 5-year all-cause mortality (hazard ratio [HR] in model 4: 0.689, 95% confidence interval [CI]: 0.551-0.862) and cardiovascular mortality (HR in model 4: 0.692, 95% CI: 0.536-0.895). After propensity score matching, the benefits of OCT guidance were consistent in terms of all-cause mortality (HR: 0.707, 95% CI: 0.548-0.913) and cardiovascular mortality (HR: 0.709, 95% CI: 0.526-0.955). CONCLUSIONS: Compared with angiography alone, OCT guidance may change reperfusion strategies and lead to better long-term survival in STEMI patients undergoing pPCI. Findings in the current observational study should be further corroborated in randomised trials.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Tomografía de Coherencia Óptica , Humanos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/cirugía , Anciano , Estudios de Seguimiento , Resultado del Tratamiento , Angiografía CoronariaRESUMEN
S100 proteins have been implicated in tumorigenesis and metastasis. As a member of S100 proteins, the role of S100A14 in carcinogenesis has not been fully understood. Here, we showed that ectopic overexpression of S100A14 promotes motility and invasiveness of esophageal squamous cell carcinoma cells. We investigated the underlying mechanisms and found that the expression of matrix metalloproteinase (MMP)-2 is obviously increased after S100A14 gene overexpression. Inhibition of MMP2 by a specific MMP2 inhibitor at least partly reversed the invasive phenotype of cells overexpressing S100A14. By serendipity, we found that S100A14 could affect p53 transactivity and stability. Thus, we further investigated whether the effect of MMP2 by S100A14 is dependent on p53. A series of biochemical assays showed that S100A14 requires functional p53 to affect MMP2 transcription, and p53 potently transrepresses the expression of MMP2. Finally, RT-quantitative PCR analysis of human breast cancer specimens showed a significant correlation between S100A14 mRNA expression and MMP2 mRNA expression in cases with wild-type p53 but not in cases with mutant p53. Collectively, our data strongly suggest that S100A14 promotes cell motility and invasiveness by regulating the expression and function of MMP2 in a p53-dependent manner.
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Neoplasias de la Mama/metabolismo , Proteínas de Unión al Calcio/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 2 de la Matriz/biosíntesis , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas de Unión al Calcio/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/genética , Invasividad Neoplásica , ARN Mensajero/biosíntesis , ARN Mensajero/genética , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Castration-resistant prostate cancer (CRPC) patients have a 14-month median survival, emphasizing the need for alternative treatments. Previously, we demonstrated that expanded high-dose natural killer (NK) cells derived from human peripheral blood exhibit therapeutic efficacy against CRPC. However, which immune checkpoint blockade promotes NK cell antitumor immunity against CRPC remains unknown. Here, we explored immune checkpoint molecule expression in NK and CRPC cells during their interactions, and identified that the T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) monoclonal antibody (mAb), vibostolimab, significantly enhanced NK cell cytotoxicity against CRPC cells and cytokine production in vitro, demonstrated by upregulation of degranulation marker CD107a and Fas-ligand (Fas-L) and increased interferon-gamma (IFN-γ) and tumor necrosis factor-alpha secretion. TIGIT blockade increased Fas-L expression and IFN-γ production via the NF-κB signaling pathway and restored degranulation via the mitogen-activated protein kinase ERK (extracellular signal-regulated kinase) kinase/ERK pathway in activated NK cells. Vibostolimab significantly enhanced NK cell antitumor effects against CRPC in two xenograft mouse models. Vibostolimab also increased T cell chemotaxis induced by activated NK cells in vitro and in vivo. Overall, blocking TIGIT/CD155 signaling enhances the antitumor effect of expanded NK cells against CRPC; this finding supports the translational application of TIGIT mAb and NK cell combination strategies from bench to bedside for CRPC treatment.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Animales , Ratones , Neoplasias de la Próstata Resistentes a la Castración/patología , Inhibidores de Puntos de Control Inmunológico/metabolismo , Células Asesinas Naturales , Receptores Inmunológicos/metabolismo , Interferón gamma/metabolismo , Modelos Animales de EnfermedadRESUMEN
Background: As a novel lipoprotein ratio, baseline low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR) is closely related to the clinical outcomes of acute coronary syndromes (ACS) after percutaneous coronary intervention. However, the pathophysiological impact of achieved LHR (aLHR) on the evolution of non-culprit lipid-rich plaques has not been systematically explored. Methods: Between September 2013 and December 2018, ACS patients with both baseline and 1-year follow-up optical coherence tomography (OCT) examinations were included in current study. They were divided into two groups according to the median value of aLHR at 1 year. Results: Overall, 132 patients with 215 lipid-rich plaques were enrolled, with a median aLHR: 1.62. There were thinner fibrous cap thickness (FCT) (133.3 [70.0-180.0] µm vs. 160.0 [100.0-208.3] µm, p = 0.025) and higher prevalence of thin-cap fibroatheroma (TCFA) (24 [22.4%] vs. 13 [12.0%], p = 0.044) and CLIMA-defined high-risk plaques (12 [11.2%] vs. 3[2.8%], p = 0.015) in the high aLHR group at 1 year. Compared with other serum lipid indexes, aLHR showed the best robust correlation with the evolution of plaque vulnerability in both unadjusted and adjusted analyses. Cut-off value of aLHR to predict the progression of maximal lipid arc and FCT was 1.51. In the adjusted model, aLHR ≥1.51 was an independent predictor of TCFA [odds ratio (OR): 3.008, 95% CI: 1.370 to 6.605, p = 0.006] at 1 year. Conclusions: aLHR correlates well with the evolution of lipid-rich plaques and vulnerable phenotypes at 1-year follow-up, which might be an important and convenient serum indicator in the secondary prevention of ACS.
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The findings on the relationship between marital status and hypertension are inconsistent. We aimed to explore age differences in their associations. We used Hainan Hypertension Survey data, including 13,088 individuals aged more than 25 years, as part of the China Hypertension Survey study, a population-based nationwide study. The marital status was classified as following three groups: the unmarried, the married, and those who formerly lived with his/her spouse. We examined the association between marital status and blood pressure levels and the odds of hypertension across different ages and sex. The participants' mean age was 49.9 ± 17 years, 49% were male, and 23% experienced hypertension. The multivariable logistic regression model showed among younger (<40 years) and older (≥60 years) participants, the married subjects appeared to have higher odds of hypertension compared with the unmarried counterparts, particular for men (Pheterogeneity = 0.039), after adjustment for age, sex, smoking, drinking, education background, employment situation, and body mass index. Compared with the unmarried and the married people, younger persons who previously had partners had a higher OR of hypertension than the older counterparts, and the ORs tended to decline with age (All Ptrend ≤ 0.005). The associations between marital status and blood pressure levels from multivariable linear regression models seemed consistent with the relationships mentioned above from logistic regression models. Our study indicates a marital status change is associated with a higher odds of hypertension, and it appears to be more obvious in young people.
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Hipertensión , Adolescente , Adulto , Anciano , Presión Sanguínea , Índice de Masa Corporal , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Modelos Logísticos , Masculino , Estado Civil , Persona de Mediana EdadRESUMEN
Esophageal squamous cell carcinoma (ESCC) is an aggressive epithelial malignancy and the underlying molecular mechanisms remain elusive. Here, we identify that the ubiquitin-specific protease 39 (USP39) drives cell growth and chemoresistance by functional screening in ESCC, and that high expression of USP39 correlates with shorter overall survival and progression-free survival. Mechanistically, we provide evidence for the role of USP39 in alternative splicing regulation. USP39 interacts with several spliceosome components. Integrated analysis of RNA-seq and RIP-seq reveals that USP39 regulates the alternative splicing events. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor and acts as a potential therapeutic target for ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Línea Celular Tumoral , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Humanos , Factores de Empalme de ARN/genética , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismoRESUMEN
BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been widely used due to their multipotency, a broad range of sources, painless collection, and compliance with standard amplification. Cell sheet technology is a tissue engineering methodology requiring scaffolds free, and it provides an effective method for cell transplantation. To improve the therapeutic efficacy, we combined hUC-MSCs with cell sheet technology to evaluate the safety and efficacy of hUC-MSC sheets in preclinical studies using appropriate animal models. METHODS: hUC-MSC sheets were fabricated by hUC-MSCs from a cell bank established by a standard operation process and quality control. Cytokine secretion, immunoregulation, and angiopoiesis were evaluated in vitro. Oncogenicity and cell diffusion assays of hUC-MSC sheets were conducted to verify the safety of hUC-MSCs sheet transplantation in mice. To provide more meaningful animal experimental data for clinical trials, porcine myocardial infarction (MI) models were established by constriction of the left circumflex, and hUC-MSC sheets were transplanted onto the ischemic area of the heart tissue. Cardiac function was evaluated and compared between the experimental and MI groups. RESULTS: The in vitro results showed that hUC-MSC sheets could secrete multiple cellular factors, including VEGF, HGF, IL-6, and IL-8. Peripheral blood mononuclear cells had a lower proliferation rate and lower TNF-α secretion when co-cultured with hUC-MSC sheets. TH1 cells had a smaller proportion after activation. In vivo safety results showed that the hUC-MSCs sheet had no oncogenicity and was mainly distributed on the surface of the ischemic myocardial tissue. Echocardiography showed that hUC-MSC sheets effectively improved the left ventricular ejection fraction (LVEF), and the LVEF significantly changed (42.25 ± 1.23% vs. 66.9 ± 1.10%) in the hUC-MSC transplantation group compared with the MI group (42.52 ± 0.65% vs. 39.55 ± 1.97%) at 9 weeks. The infarct ratio of the hUC-MSCs sheet transplantation groups was also significantly reduced (14.2 ± 4.53% vs. 4.00 ± 2.00%) compared with that of the MI group. CONCLUSION: Allogeneic source and cell bank established by the standard operation process and quality control make hUC-MSCs sheet possible to treat MI by off-the-shelf drug with universal quality instead of individualized medical technology.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Infarto del Miocardio , Animales , Humanos , Isquemia/metabolismo , Leucocitos Mononucleares , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Ratones , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Volumen Sistólico , Porcinos , Cordón Umbilical , Función Ventricular IzquierdaRESUMEN
Adoptive allogeneic natural killer (NK) cell therapy has shown promise in treating castration-resistant prostate cancer (CRPC), which is the terminal stage of prostate cancer (PCa) and incurable. Thus, we employed an efficient manufacturing method for the large-scale ex vivo expansion of high-quality NK cells from peripheral blood of healthy donors. In the present study, we evaluated the in vitro cytotoxicity of NK cells against human PCa cell lines and in vivo antitumor activity in a preclinical mouse model of CRPC. CCK-8 results demonstrated that the NK cells exerted potent cytotoxicity against all PCa cell lines in vitro. The NK cells were activated when cocultured with PCa C4-2 cells, evidenced by upregulation of the degranulation marker CD107a and secretion of cytokines (TNF-α and IFN-γ). In a xenograft mouse model of CRPC, the caliper, CT, and ultrasonography examination results showed that the size of tumors treated with NK cells was significantly smaller than that in the control group. Moreover, ultrasonography examination also indicated that the NK cell treatment evidently reduced the blood supply of the tumors and HE staining results demonstrated that the NK treatment increased the proportion of necrosis in the tumor specimen compared to PBS treatment. Meanwhile, the NK cell treatment did not cause significant serum IL-6 elevation. Therefore, our study suggested that the expanded NK cells exhibited significant cytotoxicity against PCa cell lines in vitro and excellent therapeutic efficacy against CRPC in a xenograft mouse model, which was of great value for the clinical treatment of CRPC.
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Trasplante de Células Madre Hematopoyéticas , Neoplasias de la Próstata Resistentes a la Castración , Animales , Línea Celular Tumoral , Citotoxicidad Inmunológica , Humanos , Células Asesinas Naturales/metabolismo , Masculino , Ratones , Neoplasias de la Próstata Resistentes a la Castración/terapiaRESUMEN
BACKGROUND: Patella fracture accounts for 1% of bone injury, of which anatomical reduction is of great significance to the recovery. Tension band with cannulated screw and Kirschner wire is commonly used methods for the treatment of displaced patella fracture. However, there is still some controversy on the clinical efficacy of the two treatment methods. OBJECTIVE: This study aimed at comparing the therapeutic effects of the cannulated screw and Kirschner wire tension bands on patella fracture and at providing more data basis for clinical selection of treatment methods for patella fracture. METHODS: Altogether, 146 patients with displaced patella fracture admitted to our hospital from March 2016 to February 2018 were selected and divided into two groups according to the different treatment methods. Among them, 71 patients received tension band with a cannulated screw (TBWCS group) and 75 patients received tension band with Kirschner wire (TBWKW group). Two groups of patients were compared in terms of surgical treatment effect after one year of treatment, complications within six months after the operation and operation-related indexes. The pain visual analogue scale (VAS) score, knee flexion degree, Lysholm score, and Bostman score were recorded at 1, 3, 6, and 12 months after operation, and the activity of daily living scale (ADL) score was evaluated at the last follow-up. RESULTS: During the operation of patella fracture patients, the intraoperative blood loss, hospitalization time, and knee flexion loss of patients in TBWCS group were less than those in the TBWKW group (P < 0.05), the starting time of postoperative functional exercise was earlier than that of patients in TBWKW group (P < 0.05), and the incidence rate of secondary operation was lower than that of patients in the TBWKW group (P < 0.05), but there was no statistical difference in the operation time, incision length, and postoperative fracture gap between the two groups. The results of curative effect analysis showed that the knee flexion, Lysholm score, and Bostman score of patients treated with tension band with cannulated screw were higher than those treated with Kirschner wire (P < 0.05), and VAS score was lower. Tension band with cannulated screw had a better curative effect on patella fracture (P < 0.05), lower complication rate (P < 0.05), and higher quality of life of patients (P < 0.05). CONCLUSION: Tension band with cannulated screw has a good curative effect on patella fracture, low incidence of complications, early start of postoperative functional exercise, and high quality of life.
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Fijación Interna de Fracturas/instrumentación , Fracturas Óseas/cirugía , Rótula/lesiones , Rótula/cirugía , Adulto , Anciano , Tornillos Óseos , Hilos Ortopédicos , Biología Computacional , Femenino , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Humanos , Masculino , Conceptos Matemáticos , Persona de Mediana Edad , Rótula/fisiopatología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Calidad de Vida , Rango del Movimiento ArticularRESUMEN
It has been reported microRNA-301b (miR-301b) was involved in the tumorigenesis of some cancers, but it has not been investigated in cervical carcinoma yet. In this study, miR-301b was found significantly upregulated in cervical carcinoma, and patients with high miR-301b expression had a shorter overall survival. When miR-301b was knocked down in cervical carcinoma cells, the cell growth could be significantly abolished. Our further studies showed miR-301b targeted RNF38, and inhibited its expression in cervical carcinoma cells. Moreover, RNF38 was found downregulated in cervical carcinoma, and miR-301b expression in cervical tissues was found negatively correlated with RNF38 expression. In addition, overexpression of RNF38 significantly inhibited cervical carcinoma cell growth, but overexpression of miR-301b suppressed RNF38-induced cell growth inhibition in cervical carcinoma. Collectively, this study suggested miR-301b could be a novel target for cervical carcinoma treatment.
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Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Proteínas Portadoras/genética , MicroARNs/genética , Neoplasias del Cuello Uterino/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Antagomirs/genética , Antagomirs/metabolismo , Emparejamiento Base , Secuencia de Bases , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Proliferación Celular , Cuello del Útero/metabolismo , Cuello del Útero/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Oligorribonucleótidos/genética , Oligorribonucleótidos/metabolismo , Transducción de Señal , Análisis de Supervivencia , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: To explore the regulatory mechanism of miR-137 and transcription factor 4 (TCF4) in the progression of osteoarthritis (OA). PATIENTS AND METHODS: The expressions of miR-137 and TCF4 were detected in OA cartilage tissue, chondrocytes and OA rat cartilage tissue. miR-137 and TCF4 were up-regulated or down-regulated and transfected into chondrocytes and OA rat cartilage tissue. The gene expression, protein level, cell proliferation, apoptosis and inflammatory factors were detected, respectively. LPS and anterior cruciate ligament transection (ACLT) on the right knee were used to induce chondrocyte inflammation and establish rat OA model, respectively. RESULTS: miR-137 was low expressed in cartilage tissue of OA group, while TCF4 expression and protein level were significantly higher, showing significant negative correlation. In LPS group, chondrocyte activity was significantly inhibited, cell apoptosis ability was significantly enhanced, and the levels of inflammatory factors TNF-α, IL-1ß, IL-6 were significantly increased. However, the above results were significantly improved after the up-regulation of miR-137 or down-regulation of TCF4. Double luciferase report revealed that miR-137 and TCF4 had targeted relationship. LPS induced activation of AMPK/NF-κB pathway and higher level of apoptosis. AMPK/NF-κB pathway inhibitor C could inhibit activation of this pathway, and up-regulation of miR-137 or down-regulation of TCF4 could significantly weaken the regulation of LPS on the pathway and apoptosis. Analysis of OA rat model showed that over-expression of miR-137 could inhibit up-regulation of inflammatory factors and activation of AMPK/NF-κB pathway. CONCLUSION: miR-137 targets the inhibition of TCF4 to reverse the progression of OA through the AMPK/NF-κB signaling pathway.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Condrocitos/enzimología , MicroARNs/metabolismo , FN-kappa B/metabolismo , Osteoartritis/enzimología , Factor de Transcripción 4/metabolismo , Animales , Apoptosis , Estudios de Casos y Controles , Proliferación Celular , Células Cultivadas , Condrocitos/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Osteoartritis/genética , Osteoartritis/patología , Ratas Sprague-Dawley , Transducción de Señal , Factor de Transcripción 4/genéticaRESUMEN
MicroRNA (miR)-150 has been demonstrated to protect the heart from ischemic injury. However, the protective effect of miR150 in hypoxiainjured cardiomyocytes remains unclear. The present study aimed to investigate the target gene of miR150 and the underlying molecular mechanisms of miR150 in hypoxiainduced cardiomyocyte apoptosis. Using the hypoxia model of human cardiomyocytes (HCMs) in vitro, it was demonstrated that miR150 was markedly inhibited in HCMs after hypoxia treatment. Overexpressing miR150 significantly decreased hypoxiainduced HCM death and apoptosis. In addition, GRP94 was revealed to be a direct target of miR150. Additionally, GRP94 was demonstrated to be involved in hypoxiainduced HCM apoptosis, and the protein expression levels of GRP94 were increased in HCMs in the presence of hypoxia. These findings demonstrated that miR150 is involved in hypoxiamediated gene regulation and apoptosis in HCMs. Furthermore, GRP94 knockout increased the cell viability of hypoxiaimpaired HCMs with miR150 mimic or miR150 inhibitor transfection. In conclusion, miR150 may serve a protective role in cardiomyocyte hypoxia injury, and the underlying mechanism was mediated, at least partially, by inhibiting GRP94 expression. These findings may provide a novel insight for the therapy of hypoxia-induced myocardial I/R injury.
Asunto(s)
Apoptosis/efectos de los fármacos , Glicoproteínas de Membrana/genética , MicroARNs/genética , Miocitos Cardíacos/efectos de los fármacos , Oxígeno/farmacología , Regiones no Traducidas 3' , Antagomirs/genética , Antagomirs/metabolismo , Apoptosis/genética , Secuencia de Bases , Sitios de Unión , Hipoxia de la Célula , Línea Celular , Regulación de la Expresión Génica , Genes Reporteros , Humanos , Luciferasas/genética , Luciferasas/metabolismo , Glicoproteínas de Membrana/metabolismo , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Oligorribonucleótidos/genética , Oligorribonucleótidos/metabolismo , Transducción de SeñalRESUMEN
The feasibility of three-dimensional (3D) printing technology combined with minimally invasive surgery in the treatment of pubic rami fractures was explored. From August 2015 to October 2017, a series of 30 patients who underwent surgical stabilization of their anterior pelvic ring (all utilizing the 3D printing technology) by one surgeon at a single hospital were studied. The minimally invasive incisions were made through anterior inferior cilia spine and pubic nodule. Data collected included the operative duration, the blood loss, the damage of the important tissue, the biographic union and the recovery of the function after the operation. Measurements on inlet and outlet pelvic cardiograph were made immediately post-operation and at all follow-up clinic visits. The scores of reduction and function were measured during follow-up. Results showed that the wounds of 30 patients were healed in the first stage, and there was no injury of important structures such as blood vessels and nerves. According to the Matta criteria, excellent effectiveness was obtained in 22 cases and good in 8 cases. According to the functional evaluation criteria of Majeed, excellent effectiveness was obtained in 21 cases and good in 9 cases. It was suggested that the 3D printing technology assisted by minimally invasive surgery can better evaluate the pelvic fracture before operation, which was helpful in plate modeling, and can shorten surgery duration and reduce intraoperative blood loss and complications. The positioning accuracy was improved, and better surgical result was finally achieved.
Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Impresión Tridimensional , Hueso Púbico/cirugía , Adulto , Placas Óseas , Tornillos Óseos , Femenino , Fracturas Óseas/fisiopatología , Humanos , Masculino , Hueso Púbico/fisiopatología , Fracturas de la Columna Vertebral/fisiopatología , Fracturas de la Columna Vertebral/cirugíaRESUMEN
OBJECTIVE: To evaluate the short and long-term outcomes between stenting with sirolimus eluting stent (SES) and spot stenting with small vessel stent (SVS) for treatment of small vessels with long lesions. METHODS: 306 coronary heart disease patients in need of stenting in small vessel (diameter < 3.0 mm) with long lesions (> 20 mm) were divided into 2 groups: SES group (n = 93, receiving 157 CYPHER stents) and SVS group (n = 113, receiving spot stenting tactics). The clinical characteristics, success rate of procedure, rate of in-stent restenosis, target lesion revasculation (TLR), and major adverse cardiac events (MACE) were recorded after 6-month follow-up. RESULTS: The baseline clinical and angiographic characteristics were similar between these two groups. Two CYPHER stents failed to pass the tortuous and calcified lesions in the SES group; DRIVER stents were used instead and succeeded in the passing. The rates of in-stent restenosis, TLR, and MACE of the SES group were 4.0%, 2.2%, and 3.2% respectively, all significantly, lower than those of the SVS group (26.5%, 10.6%, and 13.3% respectively, all P < 0.05). CONCLUSION: In treatment of small vessel with long lesions, the rates of in-stent restenosis, TLR, and MACE are all much lower in the SES group than in the SVS group. Spot stenting with SVS may be feasible for small vessels with long and tortuous lesions, especially for those in which SES fails to pass through.
Asunto(s)
Enfermedad Coronaria/terapia , Stents Liberadores de Fármacos , Sirolimus/administración & dosificación , Stents , Adulto , Anciano , Anciano de 80 o más Años , Angioplastia Coronaria con Balón , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
S100A7 is an EF-hand calcium-binding protein that has been suggested to be implicated in cell proliferation, migration, invasion and tumor metastasis. However, its role in cervical cancer has not yet been fully clarified. The present study used immunohistochemistry analysis of S100A7 in clinical specimens of cervical cancer to show that S100A7 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and S100A7 expression in high grade cervical intraepithelial neoplasm (CIN) was significantly higher than cervical cancer. Statistical analysis showed that S100A7 expression was associated with tumor grade (P <0.01) and lymph node metastasis (P <0.05). Functional studies showed that overexpression of S100A7 in cervical cancer cells promoted migration, invasion and metastasis of cervical cancer cells without influencing cell proliferation. Furthermore, S100A7 was found to be secreted into the conditioned media and extracellular S100A7 enhanced cell migration and invasion. Mechanistically, S100A7 bound to RAGE and activated ERK signaling pathway. And S100A7 enhanced cell mesenchymal properties and induced epithelial-mesenchymal transition. In summary, these data reveal a crucial role for S100A7 in regulating cell migration, invasion, metastasis and EMT of cervical cancer and suggest that targeting S100A7 may offer a new targeted strategy for cervical cancer.