RESUMEN
BACKGROUND: Meconium peritonitis (MP) is a rare fetal disease that needs to be urgently identified for surgical intervention. We report a series of 35 patients diagnosed prenatally with MP by magnetic resonance imaging (MRI), illustrate the imaging findings and investigate the predictive value of these findings for postpartum management. METHOD: A consecutive cohort of patients diagnosed with MP who were born at our institution from 2013 to 2018 was enrolled retrospectively. The prenatal ultrasound and MRI findings were analyzed. Fisher's exact probability test was used to evaluate the predictive value of MRI for surgical intervention between the operative group and the nonoperative group. RESULTS: Ascites (30/35) and distended bowel loops (27/35) were two of the most common prenatal MP-related findings on fetal MRI. Of the 35 infants, 26 received surgical intervention. All fetuses with MRI scans showing bowel dilatation (14/26, p = 0.048) and micro-colorectum (13/26, p = 0.013) required surgery. There were no significant differences in the number of fetuses with meconium pseudocysts and peritoneal calcifications between the two groups. CONCLUSION: Fetuses with bowel dilatation and micro-colorectum on MRI may need postpartum surgical intervention. Infants with only a small amount of ascites and slight bowel distention were likely to receive conservative treatment.
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Enfermedades Fetales/diagnóstico por imagen , Meconio/diagnóstico por imagen , Peritonitis/diagnóstico por imagen , Adulto , Estudios de Cohortes , Femenino , Enfermedades Fetales/cirugía , Edad Gestacional , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Edad Materna , Peritonitis/cirugía , Valor Predictivo de las Pruebas , Embarazo , Diagnóstico Prenatal , Estudios Retrospectivos , Ultrasonografía Prenatal , Adulto JovenRESUMEN
Cancer-associated fibroblasts (CAFs), a dominant component of the pancreatic tumor microenvironment, are mainly considered as promotors of malignant progression, but the underlying molecular mechanism remains unclear. Here, we show that SDF-1 secreted by CAFs stimulates malignant progression and gemcitabine resistance in pancreatic cancer, partially owing to paracrine induction of SATB-1 in pancreatic cancer cells. CAF-secreted SDF-1 upregulated the expression of SATB-1 in pancreatic cancer cells, which contributed to the maintenance of CAF properties, forming a reciprocal feedback loop. SATB-1 was verified to be overexpressed in human pancreatic cancer tissues and cell lines by quantitative real-time PCR, western blot, and immunohistochemical staining, which correlated with tumor progression and clinical prognosis in pancreatic cancer patients. We found that SATB-1 knockdown inhibited proliferation, migration, and invasion in SW1990 and PANC-1 cells in vitro, whereas overexpression of SATB-1 in Capan-2 and BxPC-3 cells had the opposite effect. Immunofluorescence staining showed that conditioned medium from SW1990 cells expressing SATB-1 maintained the local supportive function of CAFs. Furthermore, downregulation of SATB-1 inhibited tumor growth in mouse xenograft models. In addition, we found that overexpression of SATB-1 in pancreatic cancer cells participated in the process of gemcitabine resistance. Finally, we investigated the clinical correlations between SDF-1 and SATB-1 in human pancreatic cancer specimens. In summary, these findings demonstrated that the SDF-1/CXCR4/SATB-1 axis may be a potential new target of clinical interventions for pancreatic cancer patients.
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Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma Ductal Pancreático/genética , Quimiocina CXCL12/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Neoplasias Pancreáticas/genética , Anciano , Animales , Antimetabolitos Antineoplásicos/uso terapéutico , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Fibroblastos Asociados al Cáncer/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quimiocina CXCL12/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Humanos , Metástasis Linfática , Masculino , Proteínas de Unión a la Región de Fijación a la Matriz/antagonistas & inhibidores , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Ratones , Ratones Desnudos , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Análisis de Supervivencia , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , GemcitabinaRESUMEN
Repairing articular cartilage defects is difficult due to the hypovascular biostructure and poor self-repairing capacity of articular cartilage. Currently, mesenchymal stem cells (MSCs) with excellent differentiation potential are considered as a promising biological approach for cartilage regeneration. The effect, however, remains far from satisfactory for clinical applications owing to the main drawbacks of tracking the retention of cells and a low differentiation efficiency. As known, the nanoparticles with superparamagnetic properties has been used to monitor the MSCs in vivo through magnetic resonance imaging (MRI) in clinical application. In this study, different external and internal bio-conditions were applied to regulate the biological behavior of cells. Here, intracellular MRI contrast agents, superparamagnetic iron oxide nanocrystals (SPIONs), and a hypoxic culture environment were found to exert synergistic effects on gene and protein expression, and the cell viability, cell cycle, apoptosis, reactive oxygen species and the stem cell differentiations were measured. The levels of chondrogenic and migrant markers (including collagen II, collagen X, aggrecan, SOX9, MMPs and CXCR4) increased, triggering directional differentiation and enhancing cell migration to the inflammatory site. Moreover, SPION-labeled hypoxia-preconditioned MSCs were found without reactive oxygen species generation and transplanted into rat models with articular cartilage disorders. Interestingly, MRI and histological identification confirmed that new cartilage-like tissue was regenerated and that defects were repaired, and this method is more efficient for cartilage regeneration than SPION-labeled normoxia MSCs. The synergistic effect of hypoxia-precondition and SPIONs based cellular iron source could improve the cell migration and facilitate chondrogenic differentiation.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Diferenciación Celular , Condrogénesis , Imagen por Resonancia Magnética , Oxígeno , RatasRESUMEN
OBJECTIVE: To observe the effect of superparamagnetic iron oxide (SPIO) on the differentiation of rat bone marrow stem cells (BMSCs) into chondrocytes in vitro and explore the possible mechanism. METHODS: CCK8 assay was performed to examine the cytotoxicity of SPIO (1 and 5 µg/mL) on cultured SD rat BMSCs. Prussian blue staining and fluorescence excitation assay were used to assess the binding of the SPIO to BMSCs after the cells had been cultured in chondrocytes-induced medium in the presence of SPIO (1 and 5 µg/mL) for 9 days. The mRNA levels of COL2 α2, aggrecan and MMP13 in the cell culture were examined using Q-PCR, and the chondrogenic differentiation of the BMSCs was analyzed using alcian blue staining and immunofluorescence staining for COL2 α2. The protein levels of COL2 α2, aggrecan, MMP13, Ihh and PTHrP in the cells were examined using Western blotting. RESULTS: CCK8 assay showed no significant toxicity of SPIO on BMSCs. Compared with the control cells, the cells cultured in the presence of SPIO showed increased expressions of COL2 α2 and aggrecan and decreased expression of MMP13 at both mRNA and protein levels with also significantly increased expressions of Ihh and PTHrP proteins. CONCLUSION: SPIO can promote the differentiation of rat BMSCs into chondrocytes and up-regulate the Ihh/PTHrP signal pathway, suggesting the potential of SPIO as a new therapeutic agent for chondrocyte-related diseases.
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Diferenciación Celular , Condrocitos/citología , Compuestos Férricos/farmacología , Nanopartículas de Magnetita , Células Madre Mesenquimatosas/citología , Agrecanos/metabolismo , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células Cultivadas , Condrocitos/efectos de los fármacos , Colágeno Tipo II/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Mathematical questions related to determining the structure of a protein from NMR orientational restraints are discussed. The protein segment is a kinked alpha helix modeled as a regular alpha helix in which two adjacent torsion angles have been varied from their ideal values. Varying these torsion angles breaks the helix into two regular helical segments joined at a kink. The problem is to find the torsion angles at the kink from the relationship of the helical segments to the direction of the magnetic field.