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OBJECTIVE: To evaluate the clinical effectiveness of antibiotic bone cement combined with the lobulated perforator flap based on the descending branch of the lateral circumflex femoral artery (d-LCFA) in the treatment of infected traumatic tissue defects in the foot, in accordance with the Enhanced Recovery after Surgery (ERAS) concept. METHODS: From December 2019 to November 2022, 10 patients with infected traumatic tissue defects of the foot were treated with antibiotic bone cement combined with the d-LCFA lobulated perforator flap. The cohort comprised 6 males and 4 females, aged 21 to 67 years. Initial infection control was achieved through debridement and coverage with antibiotic bone cement, requiring one debridement in nine cases and two debridements in one case. Following infection control, the tissue defects were reconstructed utilizing the d-LCFA lobulated perforator flap, with the donor site closed primarily. The flap area ranged from 12 cm×6 cm to 31 cm×7 cm. Postoperative follow-up included evaluation of flap survival, donor site healing, and ambulatory function of the foot. RESULTS: The follow-up period ranged from 7 to 24 months, averaging 14 months. Infection control was achieved successfully in all cases. The flaps exhibited excellent survival rates and the donor site healed by first intention. Based on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, pain and function were evaluated as excellent in 3 cases, good in 5 cases, and moderate in 2 cases. CONCLUSION: The application of antibiotic bone cement combined with the d-LCFA lobulated perforator flap is an effective treatment for infected traumatic tissue defects of the foot with the advantages of simplicity, high repeatability, and precise curative effects. The application of the d-LCFA lobulated perforator flap in wound repair causes minimal damage to the donor site, shortens hospital stays, lowers medical expenses, and accelerates patient rehabilitation, aligning with the ERAS concept. Therefore, it is a practice worth promoting in clinical use.
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Antibacterianos , Cementos para Huesos , Desbridamiento , Arteria Femoral , Traumatismos de los Pies , Colgajo Perforante , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Colgajo Perforante/irrigación sanguínea , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Traumatismos de los Pies/cirugía , Cementos para Huesos/uso terapéutico , Arteria Femoral/cirugía , Desbridamiento/métodos , Adulto Joven , Procedimientos de Cirugía Plástica/métodos , Resultado del Tratamiento , Traumatismos de los Tejidos Blandos/cirugía , Estudios Retrospectivos , Cicatrización de HeridasRESUMEN
We demonstrate the rapid photodarkening (PD) phenomenon in Tm-doped fiber (TDF) core pumped by a laser at 1080 nm and the bleaching effect of deuterium (${{\rm D}_2}$D2) on PD TDF. By ${{\rm D}_2}$D2 loading for seven days, the PD-induced excess loss (PIEL) in the visible (VIS) and near-infrared (NIR) region have been largely eliminated, and no degradation was observed within 30 days. PD resistance of the ${{\rm D}_2}$D2 pretreated TDF has been investigated as well. The formation of color centers based on defects and precursors in the silica matrix and the mechanism of ${{\rm D}_2}$D2 bleaching are discussed.
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The laser performance of a high-power ytterbium-doped fiber amplifier is mainly hindered by the onset of mode instability. In this work, the slope efficiency and mode instability threshold of the ytterbium-doped fiber under various gamma-ray radiation doses have been measured. Experimental results reveal that gamma-ray radiation-induced photodarkening degrades mode instability severely, and gamma-ray radiation-induced mode instability degradation can be partly bleached by hours of pump-light injection. It is shown that gamma-ray radiation-induced photodarkening results in a steep reduction of slope efficiency and mode instability threshold; moreover, the entire irradiated fiber can be partly bleached by hours of pump-light injection and exhibits both time and gamma-ray radiation-dose saturation properties. The experimental results indicate that mode instability mitigation can be partly realized by pump-light injection and implies photodarkening suppression is beneficial for TMI mitigation, which is very promising for the advancement of high-power fiber lasers.
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We demonstrate the almost complete 2 µm laser power recovery of the gamma-ray-irradiated thulium (Tm)-doped silica fiber under deuterium loading. The optical-optical slope efficiency and the cladding absorption spectra of the Tm-doped fiber with gamma-ray irradiation and deuterium treatment have been measured for comparison. It was found that the slope efficiency of the irradiated Tm-doped fiber could be recovered to 96.1% of the pristine after deuterium bleaching, which significantly degraded from 60.7% to 25.3% after irradiation. Meanwhile, the additional absorption attenuation of the irradiated Tm-doped with D2 treatment completely vanished. Based on the comprehensive comparison of cladding absorption spectra, the probable mechanism of the deuterium bleaching effect on irradiated Tm-doped fiber has also been discussed.
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BACKGROUND: Diffusion kurtosis imaging (DKI) has the potential to provide microstructural insights into myelin and axonal pathology with additional kurtosis parameters. To our knowledge, few studies are available in the current literature using DKI by tract-based spatial statistics (TBSS) analysis in patients with multiple sclerosis (MS). The aim of this study is to assess the performance of commonly used parameters derived from DKI and diffusion tensor imaging (DTI) in detecting microstructural changes and associated pathology in relapsing remitting MS (RRMS). METHODS: Thirty-six patients with RRMS and 49 age and sex matched healthy controls underwent DKI. The brain tissue integrity was assessed by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), radial diffusivity (Dr), mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr) of DKI and FA, MD, Da and Dr of DTI. Group differences in these parameters were compared using TBSS (P < 0.01, corrected). To compare the sensitivity of these parameters in detecting white matter (WM) damage, the percentage of the abnormal voxels based on TBSS analysis, relative to the whole skeleton voxels for each parameter was calculated. RESULTS: The sensitivities in detecting WM abnormality in RRMS were MK (78.2%) > Kr (76.7%) > Ka (53.5%) and Dr (78.8%) > MD (76.7%) > FA (74.1%) > Da (28.3%) for DKI, and Dr (79.8%) > MD (79.5%) > FA (68.6%) > Da (40.1%) for DTI. DKI-derived diffusion parameters (FA, MD, and Dr) were sensitive for detecting abnormality in WM regions with coherent fiber arrangement; however, the kurtosis parameters (MK and Kr) were sensitive to discern abnormalities in WM regions with complex fiber arrangement. CONCLUSIONS: The diffusion and kurtosis parameters could provide complementary information for revealing brain microstructural damage in RRMS. Dr and DKI_Kr may be regarded as useful surrogate markers for reflecting pathological changes in RRMS.
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Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Anisotropía , Encéfalo/patología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Esclerosis Múltiple Recurrente-Remitente/patología , Sustancia Blanca/patología , Adulto JovenRESUMEN
BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is regarded as an important and promising target in the treatment of HER2-positive breast cancers. However, the correlation of clinicopathological characteristics and prognostic significance of HER2 overexpression in gastric cancer patients remains unclear. Our aim was to clarify this issue. METHODS: Embase, PubMed, and the Cochrane Library were searched for relevant articles published up to May 2016. Outcomes of interest contained sex, age, tumor size, tumor site, tumor node metastasis (TNM) stage, distant metastasis, lymph node metastasis, Lauren's classification, differentiation grade, lymphovascular invasion, neural invasion, and multivariate analysis data for overall survival. RESULTS: A total of 41 studies of 17,494 gastric cancer patients were identified with HER2 test. HER2 positive rate was 19.07% (95% CI = 9.16, 28.98). There existed statistical significance between HER2 overexpression and patients' prognosis (RR = 1.47, 95% CI = 1.09, 1.98). Male patients (OR = 1.48, 95% CI = 1.34, 1.65), proximal tumors (OR = 1.25, 95% CI = 1.07, 1.47), intestinal-type tumors (OR = 3.37, 95% CI = 2.54, 4.47), advanced stage cancers (OR = 1.35, 95% CI = 1.10, 1.66), lymph node metastasis (OR = 1.26, 95% CI = 1.14, 1.41), well-differentiated cancers (OR = 1.79, 95% CI = 1.15, 2.76), and distant metastasis (OR = 1.91, 95% CI = 1.08, 3.38) were correlated with higher HER2 expression rates. However, no statistical differences existed in age, tumor size, lymphovascular invasion, or neural invasion. Subgroup analysis revealed that HER2 expression rates reported in articles from Asian (19.52%) countries were quantitatively higher than those from European (16.91%) areas. Results were consistent with those reports that define HER2 status according to trastuzumab for gastric cancer (ToGA) criteria. CONCLUSION: This study showed that HER2 overexpression was associated with poor prognosis in gastric cancer patients. HER2 positive rates may be associated with sex, tumor site, TNM staging system, distant metastasis, lymph node metastasis, Lauren's classification, and differentiation grade in gastric cancer patients. The HER2 expression rate in Asians may be higher than that in Europeans. This study offers a convenient way for doctors to select patients for relevant HER2 detection and following treatment.
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Biomarcadores de Tumor/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Pronóstico , Neoplasias Gástricas/metabolismoRESUMEN
Tm-doped fiber laser or amplifier can be applied in varied adverse environments. In this work, we demonstrate the pump bleaching of Tm-doped silica fiber with 793nm pump source under gamma-ray irradiation in the range 50Gy-675Gy. The recovery time, the fiber slope efficiency and the fiber cladding absorption spectra after irradiation and bleaching have been measured. It is found that the recovery time and radiation induce absorption are positively associated with doses, however, the fiber slope efficiency of irradiated TDF and bleached TDF are both negatively correlated with doses. Based on the simulation of the fiber core temperature, the probable mechanism of pump bleaching is also discussed.
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OBJECTIVES: To determine whether phase-contrast X-ray imaging can be used to visualise directly the accumulated extracellular matrix proteins associated with liver fibrosis in common bile duct ligated mice. METHODS: Twenty-six-week-old C57BL female mice were randomised into three groups. In groups 1 (n = 5) and 2 (n = 10), common bile duct ligation was conducted to produce secondary biliary cirrhosis. Mouse livers were then excised 15 (group 1) and 40 days (group 2) after the ligation of the common bile duct for imaging. In the control group, the livers of 5 mice were excised 40 days after the sham operation. Images were then acquired using the analyser crystal set at different positions of the rocking curve. RESULTS: The results show that the fibrotic septa and hepatic lobules enclosed by fibrotic septa can be visualised clearly at the whole organ level via phase-contrast X-ray imaging without any contrast agent. CONCLUSION: These results suggest that phase-contrast X-ray imaging can easily reveal the accumulated extracellular matrix proteins associated with liver fibrosis without using any contrast agent and has great potential in the study of liver fibrosis.
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Medios de Contraste , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Radiografía/métodos , Animales , Biopsia con Aguja , Conducto Colédoco/cirugía , Modelos Animales de Enfermedad , Femenino , Hepatectomía/métodos , Inmunohistoquímica , Ligadura , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Valores de Referencia , Sensibilidad y Especificidad , Técnicas de Cultivo de TejidosRESUMEN
A GeO2 doped triangular-core photonic-crystal fiber (PCF) is designed and fabricated to allow the generation of a hollow beam through a nonlinear-optical transformation by femtosecond pulses at 1040 nm from a high power Yb-doped PCF laser oscillator. The hollow beam supercontinuum is obtained at far field by adjusting incident light polarization to excite the high order supermode, behaving as a mode convertor. The supercontinuum ranging from 540 to 1540 nm is achieved with an average power of 1.04 W.
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Tecnología de Fibra Óptica/instrumentación , Germanio/química , Rayos Láser , Refractometría/instrumentación , Diseño Asistido por Computadora , Diseño de Equipo , Análisis de Falla de Equipo , PorosidadRESUMEN
Objective: In order to investigate the clinical effect of side entry laparoscopic splenectomy in the treatment of splenomegaly caused by neurodegenerative diseases. Methods: 62 patients who underwent endoscopic splenectomy in our hospital from July 2020 to June 2021 were randomly divided into two groups, including 3 cases in the observation group and 31 cases in the reference group. Clinical trials were conducted to compare different laparoscopic surgery methods, and follow-up investigation records were made; the drainage time and drainage volume, postoperative bleeding volume, postoperative complications, and comprehensive effective rate of the two groups were observed and analyzed. Results: Most of the drainage volume in the observation group was less than 800 ml, and most of the drainage volume in the reference group was more than 500 ml. Compared with the reference group, the average drainage time of patients in the observation group was lower, mostly within 6 days, while the drainage time of patients in the reference group was more than 8 days. The amount of bleeding in the observation group was mostly about 500 ml, with the largest number in the range of 300-500 ml, while the amount of bleeding in the reference group was mostly 800 ml and above, with the largest number in the range of 500-800 ml. The incidence of complications in the observation group was lower than that in the reference group. The effective, markedly effective and comprehensive effective rates of patients in the observation group were higher than those in the reference group, and the ineffective rate and deterioration rate were also lower. Conclusion: The treatment of lateral laparoscopic splenectomy is very safe and effective and has obvious advantages, because it can reduce the occurrence of postoperative complications and provide a good basis for the recovery of patients. It is worthy to be widely used in clinical splenic surgery.
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Laparoscopía , Esplenectomía , Drenaje , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Esplenectomía/efectos adversos , Esplenectomía/métodos , Esplenomegalia/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the therapeutic efficacy of intravenous implanted bone marrow-derived endothelial progenitor cells (BM-EPC) preconditioned with 17ß-estradiol in ovariectomized mice model of acute myocardial infarction (AMI). METHODS: BM-EPC were cultured and identified from ovariectomized BALB/C mice tibia and femur. The ovariectomized BALB/C mice models of acute myocardial infarction (AMI) were established, and randomly divided into 17ß-estradiol + BM-EPC group (n = 6), BM-EPC group (n = 6) and control group (n = 6). Three days after AMI, BM-EPC pretreated with or without 17ß-estradiol was infused via tail vein. The equal volume of saline was infused in control group. Twenty-five days after infusion, left ventricular (LV) function and dimensions, capillary density and ratio of fibrosis area to LV area were measured. RESULTS: LV function and dimensions, capillary density and LV fibrosis were significantly improved in 17ß-estradiol + BM-EPC group than in control group [(LVDs: (3.09 ± 0.05) mm vs. (3.27 ± 0.10)mm, P < 0.05; LVDd: (4.18 ± 0.07) mm vs. (4.31 ± 0.05) mm, P < 0.05; FS: (33.0 ± 3.8)% vs. (26.0 ± 3.2)%, P < 0.05; capillary density: (1428 ± 214)/mm² vs. (1070 ± 168)/mm², P < 0.05; ratio of fibrosis: (38.8 ± 4.9)% vs. (49.0 ± 4.6)%, P < 0.05]. However, Above mentioned parameters were similar between BM-EPC group and control group (P > 0.05). CONCLUSIONS: BM-EPC preconditioned with 17ß-estradiol can enhance capillary density, decrease LV fibrosis and improve cardiac function in this mice model of AMI.
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Células Endoteliales/citología , Estradiol , Infarto del Miocardio/cirugía , Trasplante de Células Madre , Células Madre/citología , Acondicionamiento Pretrasplante/métodos , Animales , Células de la Médula Ósea/citología , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB CRESUMEN
Currently, 5-Fluorouracil (5-FU) based chemotherapy is the primary option for colorectal cancer after surgery, whereas chemotherapy resistance related mortality is observed in a large proportion of patients. Anemoside B4 (AB4) is a triterpene saponin, which exhibits a considerable activity in oncotherapy. In this study, we explored the efficacy of AB4 in FU-based chemotherapy in colorectal cancer cells and the underlying molecular mechanisms. Our results indicated a significant synergistic activity of AB4 in 5-FU treated colorectal cancer cells. Furthermore, AB4 treatment eliminated colorectal cancer stem cells by promoting apoptotic cell death in 5-FU resistant colorectal cancer cells. Mechanically, AB4 activated caspase-9 pathway in 5-FU resistant colorectal cancer cells. Elevated Src activity induced cell apoptosis and cancer stem cells elimination effects in AB4 treated colorectal cancer cells. In conclusion, AB4 showed promising sensitization effect in the FU-based chemotherapy of colorectal cancer. Our study may pave a way to ameliorate FU-based chemotherapeutic efficiency in colorectal cancer.
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Antimetabolitos Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Saponinas/uso terapéutico , Animales , Caspasa 9/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Sinergismo Farmacológico , Células HCT116/efectos de los fármacos , Humanos , Ratones Desnudos , Trasplante de Neoplasias , Células Madre Neoplásicas/efectos de los fármacosRESUMEN
OBJECTIVE: The purposes of this study were to evaluate whether a novel radiographic technique, diffraction-enhanced radiographic imaging, would render high-contrast images of mouse livers, hearts, and kidneys and to determine whether blood vessels and bile ducts can be differentiated on images of mouse livers. MATERIALS AND METHODS: For imaging of the bile ducts, mouse livers were excised 20 or 35 days after ligation of the common bile duct. Livers, hearts, and kidneys of control mice also were excised for imaging. The diffraction-enhanced imaging experiments were performed with a silicon 333 crystal diffraction plane and an 18-keV x-ray beam. The beam incident to the sample measured 20 mm (horizontal) x 11 mm (vertical). Images were acquired with the analyzer crystal set at different positions of the rocking curve. RESULTS: Only dilated bile ducts, no normal bile ducts, were found. With diffraction-enhanced imaging without a contrast agent, the blood vessels of the liver, heart, and kidney were visualized to a scale of tens of micrometers. CONCLUSION: Diffraction-enhanced imaging with a silicon 333 crystal plane had excellent contrast in the detection of blood vessels and pathologically dilated bile ducts and may be a promising radiographic technique for basic medical research.
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Conducto Colédoco/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Tecnología Radiológica/métodos , Animales , Corazón/diagnóstico por imagen , Técnicas In Vitro , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Hígado/irrigación sanguínea , Hígado/diagnóstico por imagen , Ratones , Difracción de Rayos X/métodosRESUMEN
Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging-related vascular diseases. Here, we take advantage of single-cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging-induced loss of peroxisome proliferator-activated receptor-γ coactivator-1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery-induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.
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Tejido Adiposo Pardo/citología , Envejecimiento/fisiología , Células Madre Mesenquimatosas/metabolismo , Remodelación Vascular/fisiología , Adipogénesis/genética , Adulto , Anciano , Animales , Puente de Arteria Coronaria , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Ratones Transgénicos , Persona de Mediana Edad , Neointima/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , TranscriptomaRESUMEN
Kinesin family member 4A (KIF4A) was found to be implicated in the regulation of chromosome condensation and segregation during mitotic cell division, which is essential for eukaryotic cell proliferation. However, little is known about the role of KIF4A in colorectal carcinoma (CRC). This study explored the biological function of KIF4A in CRC progression and investigated the potential molecular mechanisms involved. Here, we found that KIF4A was remarkably upregulated in primary CRC tissues and cell lines compared with paired non-cancerous tissues and normal colorectal epithelium. Elevated expression of KIF4A in CRC tissues was significantly correlated with clinicopathological characteristics in patients as well as with shorter overall and disease-free cumulative survival. Multivariate Cox regression analysis revealed that KIF4A was an independent prognostic factor for poor survival in human CRC patients. Functional assays, including a CCK-8 cell proliferation assay, colony formation analysis, cancer xenografts in nude mice, cell cycle and apoptosis analysis, indicated that KIF4A obviously enhanced cell proliferation by promoting cell cycle progression in vitro and in vivo. Furthermore, gene set enrichment analysis, Luciferase reporter assays, and ChIP assays revealed that KIF4A facilitates cell proliferation via regulating the p21 promoter, whereas KIF4A had no effect on cell apoptosis. In addition, Transwell analysis indicated that KIF4A promotes migration and invasion in CRC. Taken together, these findings not only demonstrate that KIF4A contributes to CRC proliferation via modulation of p21-mediated cell cycle progression but also suggest the potential value of KIF4A as a clinical prognostic marker and target for molecular treatments.
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Ciclo Celular , Neoplasias Colorrectales/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Cinesinas/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Supervivencia sin Enfermedad , Femenino , Células HCT116 , Humanos , Cinesinas/genética , Masculino , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Tasa de SupervivenciaRESUMEN
BACKGROUND: Silkworm genetic engineering is widely used in gene function, silk engineering and disease-resistant engineering in most of Asia. Some of the earliest promoter elements are used to control the development of silkworm transgenic expression and gene therapy. However, the low expression and specificity of natural promoters limit the applications of genetic engineering. To construct a highly efficient synthetic inducible promoter in the Bombyx mori (Lepidoptera), we analyzed the regulatory elements and functional regions of the B. mori nucleopolyhedrovirus 39 K promoter. RESULTS: Truncated mutation analysis of the 39 K promoter showed that the transcriptional regulatory region spanning positions - 573 to - 274 and + 1 to + 62 are essential for virus-inducible promoter activity. Further investigations using the electrophoretic mobility shift assay revealed that the baculovirus IE-1 protein binds to the 39 K promoter at the - 310 to - 355 region, and transcription activates the expression of 39 K promoter assay. Finally, we successfully constructed a synthetic inducible promoter that increased the virus-inducing activity of other promoters using the baculovirus-inducible transcriptional activation region that binds to specific core elements of 39 K (i.e., spanning the region - 310 to - 355). CONCLUSIONS: In summary, we constructed a novel, synthetic, and highly efficient biological tool, namely, a virus-inducible 39 K promoter, which provides endless possibilities for future research on gene function, gene therapy, and pest control in genetic engineering.
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OBJECTIVE: To explore the effects of SR59230A on the tension and microRNA (miRNA) expression of rat thoracic aorta. METHODS: Forty-four SD rats were used in the experiment. Twenty-four rats were used to observe the effect of SR on the tension of thoracic aortic rings. Another 20 rats were randomly divided into control (n=10) and SR group(n=10). Rats in SR group were injected SR intraperitoneally,and in control group were given 0.9% of saline. After 5 weeks, the blood pressure of all rats were measured. Then the tension to NA and the expression of miRNA of thoracic aorta rings were measured. RESULTS: (1) The tension of thoracic aortic rings responding to 30 mmol/LKCl were increased by pretreatment of SR (P<0.05); (2) After 5 weeks injection of SR, systolic pressure was increased (P<0.05); (3) The tension in SR group was increased in presence of 1 µmol/L and 10 µmol/L of NA (P<0.05,P<0.01). (4) After 5 weeks of SR in vivo application,18 miRNA were down-regulated, 7 of them had statistical significance, they were rno-miR-143-3p, rno-miR-29b-3p, rno-miR-31a-5p, rno-let-7b-5p, rno-miR-214-3p, rno-miR-222-3p and rno-miR-352; 11 miRNA were up-regulated, 4 of them had statistical significance, they were rno-miR-206-3pãrno-miR-223-3pãrno-miR-342-3p and rno-miR-499-5p respectively. CONCLUSIONS: SR59230A increased the tension of rat thoracic aorta. In vivo administration of SR led to increase of systolic pressure of rat,down-regulation of rno-miR-143-3pãrno-miR-29b-3pãrno-miR-31a-5pãrno-let-7b-5pãrno-miR-214-3pãrno-miR-222-3pãrno-miR-352 and up-regulation of rno-miR-206-3pãrno-miR-223-3pãrno-miR-342-3p and rno-miR-499-5p.
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Antagonistas de Receptores Adrenérgicos beta 3/farmacología , Aorta Torácica/efectos de los fármacos , MicroARNs/metabolismo , Propanolaminas/farmacología , Animales , Aorta Torácica/metabolismo , Regulación hacia Abajo , Ratas , Ratas Sprague-DawleyRESUMEN
Formyl peptide receptor 2 (FPR2), a classical chemoattractant receptor of G-protein-coupled receptors, is reported to be involved in invasion and metastasis of some cancers, but the role of FPR2 in gastric cancer (GC) has not yet been elucidated. In this study, we found that the levels of FPR2 expression in GC were positively correlated with invasion depth, lymph node metastasis and negatively correlated with the patients' overall survival. Multivariate analysis indicated that FPR2 expression was an independent prognostic marker for GC patients. FPR2-knockdown significantly abrogated the migration and invasion stimulated by Hp(2-20) and Ac(2-26), two well-characterized ligands for FPR2 in GC cells. FPR2 deletion also reduced the tumorigenic and metastatic capabilities of GC cells in vivo. Mechanistically, stimulation with FPR2 ligands resulted in down-regulation of E-cadherin and up-regulation of vimentin, which were reversed by FPR2 knock-down, implying the involvement of epithelial-mesenchymal transition (EMT). Moreover, the activation of FPR2 was accompanied with ERK1/2 phosphorylation, which could be attenuated by FPR2 silencing or treatment with MEK inhibitor, PD98059. Altogether, our results demonstrate that FPR2 is functionally involved in invasion and metastasis, and potentially acts as a novel prognostic marker as well as a potential therapeutic target in human GC.
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Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Recurrencia Local de Neoplasia/diagnóstico , Receptores de Formil Péptido/genética , Receptores de Lipoxina/genética , Neoplasias Gástricas/diagnóstico , Anciano , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores de Tumor/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Femenino , Humanos , Metástasis Linfática , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Clasificación del Tumor , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Fosforilación , Pronóstico , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptores de Formil Péptido/antagonistas & inhibidores , Receptores de Formil Péptido/metabolismo , Receptores de Lipoxina/antagonistas & inhibidores , Receptores de Lipoxina/metabolismo , Transducción de Señal , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia , Vimentina/genética , Vimentina/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
3',5'-AMP Cíclico Fosfodiesterasas/genética , Cuerpo Estriado/patología , Degeneración Nerviosa/congénito , Temblor , Adulto , Anciano , Cuerpo Estriado/fisiopatología , Femenino , Humanos , Degeneración Nerviosa/complicaciones , Degeneración Nerviosa/diagnóstico , Degeneración Nerviosa/genética , Degeneración Nerviosa/fisiopatología , Linaje , Temblor/etiología , Temblor/genéticaRESUMEN
STUDY DESIGN: A microRNA (miRNA) study. OBJECTIVE: The purpose of this study was to identify intervertebral disc degeneration (IDD)-specific miRNAs, followed by functional validation of results. SUMMARY OF BACKGROUND DATA: IDD is the major contributor to back radicular pain, and the molecular mechanisms underlying this disease are not completely understood. Accumulating evidence suggests that miRNAs play an important role in IDD, but the role of specific miRNAs involved in this disease remains elusive. METHODS: An initial screening of nucleus pulposus (NP) tissues, miRNA expression by miRNA microarray, was performed using samples from 10 patients with degenerative disc disease and 10 patients with lumbar fracture (as controls). Subsequently, differential expression was validated using quantitative reverse transcriptase PCR (qRT-PCR). The level of differentially expressed miRNAs in degenerative NP tissues was investigated, and then functional analysis of the miRNAs in regulating collagen II expression was carried out. Western blotting and luciferase reporter assays were also used to detect the target gene. RESULTS: We identified 23 miRNAs that were differentially expressed (16 upregulated and 7 downregulated) in patients compared with controls. After qRT-PCR confirmation, miR-27b was significantly downregulated in degenerative NP tissues when compared with controls. Moreover, its level was correlated with grade of disc degeneration. Overexpression of miR-27b promoted type II collagen expression in NP cells. Bioinformatics target prediction identified matrix metalloproteinase 13 (MMP13) as a putative target of miR-27b. Futhermore, luciferase reporter assays demonstrated that miR-27b directly targets MMP13 and affects the protein expression of MMP13 in NP cells. Expression of MMP13 negatively correlated with miR-27b expression in degenerative NP tissues. CONCLUSION: The downregulation of miR-27b induces type II collagen loss by directly targeting MMP13, leading to the development of IDD. Our study also underscores the potential of miR-27b as a novel therapeutic target in human IDD. LEVEL OF EVIDENCE: 3.