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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
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: 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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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
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: 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
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
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
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
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
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.
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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
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.
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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
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.
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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
S100A1 is a calcium-binding protein belonging to the family of S100 proteins, and is highly expressed in ovarian cancer. However, its role in ovarian cancer has not yet been fully elucidated. In this study, we examined S100A1 expression in ovarian cancer tissues and normal tissue controls and analyzed the correlation between S100A1 expression and clinicopathological parameters. We found that S100A1 expression was significantly upregulated in ovarian cancer tissues compared with fallopian and normal ovarian epithelium tissues and was significantly associated with lymph node metastasis and International Federation of Gynecology and Obstetrics (FIGO) stages and tumor grades. We then investigated the biological functions of S100A1 in ovarian cancer by cell proliferation, fluorescence-activated cell sorting (FACS), and migration and invasion assays. The results indicated that S100A1 enhanced the ovarian cancer cell proliferation and migration. Together, our findings demonstrated that S100A1 plays an important role in the malignancy of ovarian cancer, and serves as a useful marker for the detection of ovarian malignancy.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Movimiento Celular , Proliferación Celular , Proteínas de Neoplasias/metabolismo , Neoplasias Ováricas/metabolismo , Proteínas S100/metabolismo , Adulto , Anciano , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patologíaRESUMEN
Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive tumors in Asia. Recent researches demonstrate that miRNAs are involved in the development of ESCC. In this study, we identified a miRNA cluster, termed miR-99b/let-7e/miR-125a as pro-metastasis oncomir. Overexpression of this miRNA cluster promoted ESCC cell migration and invasion in vitro and induced an experimental metastasis in vivo. ZEB1 was discovered to bind to the promoter region of miR-99b/let-7e/miR-125a cluster and regulate the expression of miRNAs at transcriptional level. Knockdown of ZEB1 resulted in a decrease of both mature and primary miRNAs. Further research revealed AT-rich interaction domain 3A (ARID3A) as a direct target of miR-99b/let-7e/miR-125a cluster. Reduced ARID3A phenocopied miR-99b/let-7e/miR-125a overexpression, and elevated ARID3A counteracted the pro-metastasis effect of miR-99b/let-7e/miR-125a. Moreover, ARID3A was downregulated by ZEB1 in a miR-99b/let-7e/miR-125a dependent manner. Collectively, our study sheds light on the essential role of miR-99b/let-7e/miR-125a cluster in tumor metastasis.
Asunto(s)
Carcinoma de Células Escamosas/genética , Movimiento Celular , Neoplasias Esofágicas/genética , MicroARNs/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Animales , Sitios de Unión , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Línea Celular Tumoral , Proliferación Celular , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones SCID , MicroARNs/metabolismo , Invasividad Neoplásica , Regiones Promotoras Genéticas , Interferencia de ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética , Transfección , Carga Tumoral , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismoRESUMEN
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.
Asunto(s)
Proteína A7 de Unión a Calcio de la Familia S100/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Transición Epitelial-Mesenquimal , Femenino , Células HEK293 , Células HeLa , Humanos , Inmunohistoquímica , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteína A7 de Unión a Calcio de la Familia S100/biosíntesis , Proteína A7 de Unión a Calcio de la Familia S100/genética , Transfección , Neoplasias del Cuello Uterino/genética , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/patologíaRESUMEN
Metastasis is a multi-step process. Tumor cells occur epithelial-mesenchymal transition (EMT) to start metastasis, then, they need to undergo a reverse progression of EMT, mesenchymal-epithelial transition (MET), to colonize and form macrometastases at distant organs to complete the whole process of metastasis. Although microRNAs (miRNAs) functions in EMT process are well established, their influence on colonization and macrometastases formation remains unclear. Here, we established an EMT model in MCF-10A cells with SNAI1 overexpression, and characterized some EMT-related microRNAs. We identified that miR-182, which was directly suppressed by SNAI1, could enable an epithelial-like state in breast cancer cells in vitro, and enhance colonization and macrometastases in vivo. Subsequent studies showed that miR-182 exerted its function through targeting its suppressor SNAI1. Moreover, higher expression level of miR-182 was detected in metastatic lymph nodes, compared with paired primary tumor tissues. In addition, the expression level of miR-182 was negatively correlated with that of SNAI1 in these clinical specimens. Taking together, our findings describe the role of miR-182 in colonization and macrometastases in breast cancer for the first time, and provide a promise for diagnosis or therapy of breast cancer metastasis.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , MicroARNs/genética , Factores de Transcripción de la Familia Snail/genética , Animales , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Células MCF-7 , Ratones , Metástasis de la Neoplasia , Trasplante de Neoplasias , Regulación hacia ArribaRESUMEN
BACKGROUND: Angiotensin II receptor blockers (ARBs) is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R), in essential hypertensive patients at low-medium risk. METHODS AND FINDINGS: A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP) was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (P<0.01). The rate of effective blood pressure control in Allisartan Isoproxil group was significantly higher than in placebo group at week 4 (61.3% vs 50.0%, P<0.05) and week 8 (67.2% vs 48.6%, P<0.01). In terms of safety and tolerability, there were no report of death and serious adverse event (SAE) in all subjects. There was no difference of frequency between two groups in adverse event (AE) and adverse drug reaction (ADR) (P>0.05). No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study. CONCLUSIONS/SIGNIFICANCE: Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk. TRIAL REGISTRATION: http://www.chictr.org/cn/ ChiCTR-TRC-10000886.