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The efficiency of RNA interference (RNAi) has always limited the research on the phenotype innovation of Lepidoptera insects. Previous studies have found that double-stranded RNA-degrading enzyme (dsRNase) is an important factor in RNAi efficiency, but there have been no relevant reports in butterflies (Papilionoidea). Papilio xuthus is one of the important models in butterflies with an extensive experimental application value. To explore the effect of dsRNase in the RNAi efficiency on butterflies, six dsRNase genes (PxdsRNase 1-6) were identified in P. xuthus genome, and their dsRNA-degrading activities were subsequently detected by ex vivo assays. The result shows that the dsRNA-degrading ability of gut content (<1 h) was higher than hemolymph content (>12 h). We then investigated the expression patterns of these PxdsRNase genes during different tissues and developmental stages, and related RNAi experiments were carried out. Our results show that different PxdsRNase genes had different expression levels at different developmental stages and tissues. The expression of PxdsRNase2, PxdsRNase3, and PxdsRNase6 were upregulated significantly through dsGFP injection, and PxdsRNase genes can be silenced effectively by injecting their corresponding dsRNA. RNAi-of-RNAi studies with PxEbony, which acts as a reporter gene, observed that silencing PxdsRNase genes can increase RNAi efficiency significantly. These results confirm that silencing dsRNase genes can improve RNAi efficiency in P. xuthus significantly, providing a reference for the functional study of insects such as butterflies with low RNAi efficiency.
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Mariposas Diurnas , Animales , Mariposas Diurnas/genética , Interferencia de ARN , ARN Bicatenario , Insectos/genética , Silenciador del GenRESUMEN
BACKGROUND: Anesthesia for spinal muscular atrophy (SMA) patients undergoing spinal deformity surgery is challenging. We report an unusual case of an SMA girl who developed severe intraoperative hypoxemia and hypotension during posterior spinal fusion related with surgical positioning. CASE PRESENTATION: A 13-yr-old girl diagnosed with SMA type 2, severe kyphoscoliosis and thoracic deformity was scheduled for elective posterior spinal fusion. She developed severe hypoxemia and profound hypotension intraoperatively in the prone position with surgical table tilted 45° to the right. Though transesophageal echocardiography (TEE) could not be performed due to limited mouth opening, her preoperative computed tomography revealed a severely distorted thoracic cavity with much reduced volume of the right side. A reasonable explanation was when the surgeons performed surgical procedure with the tilted surgical table, the pressure was directly put on the shortest diameter of the significantly deformed thoracic cavity, causing severe compression of the pulmonary artery, resulting in both hypoxemia and hypotension. The patient stabilized when the surgical table was tilted back and successfully went through the surgery in the leveled prone position. CONCLUSIONS: Spinal fusion surgery is beneficial for SMA patients in preventing scoliosis progression and improving ventilation. However, severe scoliosis and thoracic deformities put them at risk of both hemodynamic and respiratory instability during surgical positioning. When advanced monitoring like TEE is not practical intraoperatively, preoperative imaging may help with differential diagnosis, and guide the surgical positioning to minimize mechanical compression of the thoracic cavity, thereby helping the patient complete the surgery safely.
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Hipotensión , Atrofia Muscular Espinal , Escoliosis , Fusión Vertebral , Femenino , Humanos , Hipotensión/etiología , Hipoxia/complicaciones , Atrofia Muscular Espinal/complicaciones , Estudios Retrospectivos , Escoliosis/cirugía , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Resultado del Tratamiento , AdolescenteRESUMEN
BACKGROUND: Individuals with atrial fibrillation (AF) are at an increased risk for stroke. Early detection of undiagnosed AF by screening is recommended. Single-lead electrocardiogram (ECG) is the most widely used technology in AF detection. Several systematic reviews on the diagnostic accuracy of single-lead ECG devices for AF detection have been performed but have yielded inconclusive results. AIMS: The aim of this study was to synthesize the available evidence on the effectiveness of single-lead ECG devices in detecting AF. METHODS: An overview of systematic reviews was conducted. Five English databases (Cochrane Database of Systematic Reviews, PubMed, Embase, Ovid, and Web of Science) and two Chinese databases (Wanfang and CNKI) were searched from inception to July 31, 2021. Systematic reviews that examined the accuracy of tools based on single-lead ECG technology for detecting AF were included. A narrative data synthesis was performed. RESULTS: Eight systematic reviews were finally included. Systematic reviews with meta-analysis showed that single-lead ECG-based devices had good sensitivity and specificity (both ≥90%) in detecting AF. According to subgroup analysis, the sensitivities of tools used in populations with a history of AF were all >90%. However, among handheld and thoracic placed single-lead ECG devices, large variations in diagnostic performance were observed. LINKING EVIDENCE TO ACTION: Single-lead ECG devices can potentially be used for AF detection. Due to the heterogeneity in the study population and tools, future studies are warranted to explore the suitable circumstances in which each tool could be applied for AF screening in an effective and cost-effective manner.
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Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Revisiones Sistemáticas como Asunto , Electrocardiografía/métodos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective haematopoiesis and immune deregulation. Emerging evidence has shown the effect of bone marrow (BM) endothelial progenitor cells (EPCs) in regulating haematopoiesis and immune balance. However, the number and functions of BM EPCs in patients with different stages of MDS remain largely unknown. METHODS: Patients with MDS (N = 30), de novo acute myeloid leukaemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. MDS patients were divided into lower-risk MDS (N = 15) and higher-risk MDS (N = 15) groups according to the dichotomization of the Revised International Prognostic Scoring System. Flow cytometry was performed to analyse the number of BM EPCs. Tube formation and migration assays were performed to evaluate the functions of BM EPCs. In order to assess the gene expression profiles of BM EPCs, RNA sequencing (RNA-seq) were performed. BM EPC supporting abilities of haematopoietic stem cells (HSCs), leukaemia cells and T cells were assessed by in vitro coculture experiments. RESULTS: Increased but dysfunctional BM EPCs were found in MDS patients compared with HDs, especially in patients with higher-risk MDS. RNA-seq indicated the progressive change and differences of haematopoiesis- and immune-related pathways and genes in MDS BM EPCs. In vitro coculture experiments verified that BM EPCs from HDs, lower-risk MDS, and higher-risk MDS to AML exhibited a progressively decreased ability to support HSCs, manifested as elevated apoptosis rates and intracellular reactive oxygen species (ROS) levels and decreased colony-forming unit plating efficiencies of HSCs. Moreover, BM EPCs from higher-risk MDS patients demonstrated an increased ability to support leukaemia cells, characterized by increased proliferation, leukaemia colony-forming unit plating efficiencies, decreased apoptosis rates and apoptosis-related genes. Furthermore, BM EPCs induced T cell differentiation towards more immune-tolerant cells in higher-risk MDS patients in vitro. In addition, the levels of intracellular ROS and the apoptosis ratios were increased in BM EPCs from MDS patients, especially in higher-risk MDS patients, which may be therapeutic candidates for MDS patients. CONCLUSION: Our results suggest that dysfunctional BM EPCs are involved in MDS patients, which indicates that improving haematopoiesis supporting ability and immuneregulation ability of BM EPCs may represent a promising therapeutic approach for MDS patients.
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Células Progenitoras Endoteliales , Síndromes Mielodisplásicos , Apoptosis , Médula Ósea , Células Madre Hematopoyéticas , Humanos , Síndromes Mielodisplásicos/genéticaRESUMEN
A miniaturized fiber optic hydrophone (FOH) based on a composite metal diaphragm with an air back cavity and a high finesse extrinsic Fabry-Perot interferometric (EFPI) scheme for low-frequency underwater acoustic sensing is proposed and experimentally demonstrated in this paper. A composite metal diaphragm is used to improve the stability of the hydrophone. A balance channel is used to equilibrate the hydrostatic pressure and maintain an air cavity, which improves the mechanical sensitivity. In addition, a white light interferometry (WLI) phase demodulation is used to demodulate the high finesse interferometer consisted of the fiber collimator end face and the diaphragm, which improves the phase sensitivity. Experimental results show that the enhanced phase sensitivity of the hydrophone is about -122.5â dB re 1â rad/µPa @ 200â Hz and the sensitivity fluctuation is below 2.5â dB between 3â Hz and 400â Hz, while the minimal detectable pressure (MDP) is 63.7 µPa/Hz1/2 @ 400â Hz. Due to its miniaturized structure and high sensitivity, the FOH may have an enormous potential in underwater target detection.
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Bone marrow (BM) endothelial progenitor cell (EPC) damage of unknown mechanism delays the repair of endothelial cells (EC) and recovery of hematopoiesis after chemo-radiotherapy. We found increased levels of the glycolytic enzyme PFKFB3 in the damaged BM EPC of patients with poor graft function, a clinical model of EPC damage-associated poor hematopoiesis after allogeneic hematopoietic stem cell transplantation. Moreover, in vitro the glycolysis inhibitor 3-(3-pyridinyl)- 1-(4-pyridinyl)-2-propen-1-one (3PO) alleviated the damaged BM EPC from patients with poor graft function. Consistently, PFKFB3 overexpression triggered BM EPC damage after 5-fluorouracil treatment and impaired hematopoiesis-supporting ability in vitro. Mechanistically, PFKFB3 facilitated pro-apoptotic transcription factor FOXO3A and expression of its downstream genes, including p21, p27, and FAS, after 5-fluorouracil treatment in vitro. Moreover, PFKFB3 induced activation of NF-κB and expression of its downstream adhesion molecule E-selectin, while it reduced hematopoietic factor SDF-1 expression, which could be rescued by FOXO3A silencing. High expression of PFKFB3 was found in damaged BM EC of murine models of chemo-radiotherapy-induced myelosuppression. Furthermore, a murine model of BM EC-specific PFKFB3 overexpression demonstrated that PFKFB3 aggravated BM EC damage, and impaired the recovery of hematopoiesis after chemotherapy in vivo, effects which could be mitigated by 3PO, indicating a critical role of PFKFB3 in regulating BM EC damage. Clinically, PFKFB3-induced FOXO3A expression and NF-κB activation were confirmed to contribute to the damaged BM EPC of patients with acute leukemia after chemotherapy. 3PO repaired the damaged BM EPC by reducing FOXO3A expression and phospho-NF-κB p65 in patients after chemotherapy. In summary, our results reveal a critical role of PFKFB3 in triggering BM EPC damage and indicate that endothelial-PFKFB3 may be a potential therapeutic target for myelosuppressive injury.
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Células Progenitoras Endoteliales , FN-kappa B , Animales , Humanos , Ratones , Médula Ósea/metabolismo , Selectina E/metabolismo , Células Progenitoras Endoteliales/metabolismo , Fluorouracilo/farmacología , Glucólisis , FN-kappa B/metabolismo , Fosfofructoquinasa-2/genética , Fosfofructoquinasa-2/metabolismoRESUMEN
In this paper, a novel inline optical fiber sensor for curvature and temperature measurement simultaneously has been proposed and demonstrated, which can measure two parameters with very little crosstalk. Two combinational mechanisms of anti-resonant reflecting optical waveguide and inline Mach-Zehnder interference structure are integrated into a 3 mm-long single hole twin suspended core fiber (SHTSCF). The 85 µm hole core gives periodic several dominant resonant wavelengths in the optical transmission spectrum, acting as the anti-resonant reflecting optical waveguide (ARROW). The modes in two suspended cores and the cladding form the comb pattern. Reliable sensor sensitivity can be obtained by effective experiments and demodulation. Through intensity demodulation of the selected dip of Gaussian fitting, the curvature sensitivity can be up to -7.23 dB/m-1. Through tracking the MZI dip for wavelength demodulation, the temperature sensitivity can be up to 28.8 pm/°C. The sensor is simple in structure, compact, and has good response, which can have a bright application in a complex environment.
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Elderly individuals exhibit unbalanced bone marrow (BM) effector T cell subset differentiation, such as increased T helper type 1 (Th1) and T cytotoxic type 1 (Tc1) cell frequencies, but the underlying mechanism is still unclear. Endothelial cells (ECs), which are instructive components of the BM microenvironment, exhibit the phenotype of semi-professional antigen-presenting cells and regulate T cell recruitment and activation. Thus, we compared the frequency and function of BM ECs, especially their capacity to regulate effector T cell subsets, between young and elderly healthy individuals, and explored the underlying mechanism of this immunomodulatory discrepancy. Although the young and elderly EC percentages were comparable, young ECs showed fewer reactive oxygen species and better migratory and tube-forming abilities than elderly ECs. Notably, increased T cell activation molecules and inflammatory cytokines were found in elderly ECs which regulated T cells to differentiate into more proinflammatory T cells, including Th1 and Tc1 cells, than young ECs.
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Células de la Médula Ósea/inmunología , Diferenciación Celular/inmunología , Células Endoteliales/inmunología , Linfocitos T Citotóxicos/inmunología , Células TH1/inmunología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Prolonged hypotension is a common complication after resection of pheochromocytoma (PCC) or paraganglioma (PGL). The objective of our study was to identify preoperative or intraoperative clinical factors that can predict prolonged hypotension after PCC/PGL resection. PATIENTS AND METHODS: A total of 414 patients who underwent resection of PCC or PGL at our institution between January 2013 and January 2020 were included. Patients were divided into two groups according to whether or not vasopressor support was required postoperatively. Associations between preoperative and intraoperative variables and prolonged hypotension were evaluated. RESULTS: Two hundred and one (48.6%) patients had postoperative hypotension that required vasopressor support with a median duration of 20 h. Multivariable analysis demonstrated that increased 24-h urinary norepinephrine (NE) levels (odds ratio [OR] = 1.091, 95% confidence interval [CI]: 1.052-1.132, p < .001), longer operative time (OR = 1.008, CI: 1.004-1.011, p < .001) and lower preoperative phenoxybenzamine dose (OR = 0.336, CI: 0.150-0.753, p = .008) were predictors of prolonged hypotension. Moreover, operative time, body mass index, 24-h urinary level of NE and preoperative phenoxybenzamine dose were significantly correlated with the duration of postoperative vasopressor support. CONCLUSIONS: Increased urine NE level, longer operative time and lower preoperative phenoxybenzamine dose were predictors of prolonged hypotension requiring vasopressor support. Clinicians can identify these factors to manage their patients better and prevent severe complications.
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Neoplasias de las Glándulas Suprarrenales , Hipotensión , Paraganglioma , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/cirugía , Humanos , Hipotensión/tratamiento farmacológico , Hipotensión/etiología , Paraganglioma/tratamiento farmacológico , Paraganglioma/cirugía , Feocromocitoma/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: Prepump arterial (Pa) pressure indicates the ease or difficulty with which the blood pump can draw blood from the vascular access (VA) during hemodialysis. Some studies have suggested that the absolute value of the Pa pressure to the extracorporeal blood pump flow (Qb) ratio set on the machine (|Pa/Qb|) can reflect the dysfunction of VA. This study was conducted to explore the impact of arteriovenous fistula (AVF) dysfunction and to explore the clinical reference value of |Pa/Qb|. METHODS: We retrospectively identified adults who underwent hemodialysis at 3 hospitals. Data were acquired from electronic health records. We evaluated the pattern of the association between |Pa/Qb| and AVF dysfunction during 1 year using a Cox proportional hazards regression model with restricted cubic splines. Then, the patients were grouped based on the results, and hazard ratios were compared for different intervals of |Pa/Qb|. RESULTS: A total of 490 patients were analyzed, with an average age of 55 (44, 66) years. There were a total of 85 cases of AVF dysfunction, of which 50 cases were stenosis and 35 cases were thrombosis. There was a U-shaped association between |Pa/Qb| and the risk of AVF dysfunction (p for nonlinearity <0.001). |Pa/Qb| values <0.30 and >0.52 increased the risk of AVF dysfunction. Compared with the group with a |Pa/Qb| value between 0.30 and 0.52, the groups with |Pa/Qb| <0.30 and |Pa/Qb| >0.52 had a 4.04-fold (p = 0.002) and 3.41-fold (p < 0.001) greater risk of AVF dysfunction, respectively. CONCLUSIONS: The appropriate range of |Pa/Qb| is between 0.30 and 0.52. When |Pa/Qb| is <0.30 or >0.52, the patient's AVF function or Qb setting should be reevaluated to prevent subsequent failure.
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Presión Arterial , Fístula Arteriovenosa/etiología , Diálisis Renal/efectos adversos , Adulto , Anciano , Fístula Arteriovenosa/fisiopatología , Fístula Arteriovenosa/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the correlations between the habit of betel quid and areca nut (BQ-AN) chewing and the prognosis of oral cancer (OC). METHODS: We performed a systematic review and meta-analysis to clarify this issue. Data searches were performed using PubMed, Web of Science, Epistemonikos, and Embase databases through November 2019. The primary outcome was the difference in the prognosis of OC between BQ-AN chewers and non-chewers, measured in terms of 5-year overall survival (OS) and 5-year disease-specific survival (DSS) log (HR) reported in articles. The pooled HR with 95% CI of 5-year OS and 5-year DSS was calculated using a fixed-effects model. RESULTS: Ten articles with eleven OS or DSS survival studies (one of the articles contained two studies), which were published between 2003 and 2017, were eligible for inclusion in the present study. All the 11 studies were observational studies, among which 10 were retrospective and 1 was prospective. One study measured both OS and DSS. Eight studies, with a total of 2,761 patients, used 5-year OS as the primary endpoint and four studies, with a total of 2,551 patients, used 5-year DSS. Overall, the pooled HR evaluating BQ-AN chewers was 1.26 (95% CI: 1.09-1.46) for 5-year OS and 1.40 (95% CI: 1.15-1.70) for 5-year DSS, compared with non-chewers. There was a significant association between BQ-AN chewing and OC survival. CONCLUSIONS: Betel quid and areca nut chewing is significantly associated with poor prognosis in patients with OC.
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Areca , Neoplasias de la Boca , Areca/efectos adversos , Humanos , Masticación , Neoplasias de la Boca/etiología , Nueces , Pronóstico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a high rate of new mutation and variable expression. Diffuse neurofibroma of the epidermis invading deeper organs is rare.We report a case of diffuse subcutaneous neurofibroma in the thoracoabdominal wall which had invaded the diaphragm and caused diaphragmatic eventration. CASE PRESENTATION: We describe a patient with diffuse neurofibroma of the chest and abdomen who was admitted to the hospital due to sudden abdominal pain and a possible diaphragmatic hernia. We performed thoracotomy and found that the neurofibroma had invaded the diaphragm and caused diaphragmatic eventration. CONCLUSIONS: This occurrence has not been reported, and it shows that although neurofibromatosis is a benign disease, it still has the biological behavior of a malignant tumor and may cause a serious impact on and damage to other organs.
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Pared Abdominal , Eventración Diafragmática , Hernias Diafragmáticas Congénitas , Neurofibroma , Diafragma/diagnóstico por imagen , Diafragma/cirugía , Humanos , Neurofibroma/diagnóstico por imagen , Neurofibroma/cirugíaRESUMEN
Transmission of varicella occurs frequently in schools and households. We investigated the characteristics of varicella cases derived from within-household transmission and the modes of varicella transmission between school and household settings in Shanghai, China, from 2009 to 2018. Within-household transmission occurred in 278 households, of which 134 transmission events were between children. Sixty-one household varicella transmission events may be attributed to isolation procedures for infected students during school outbreaks, and 7.6% of school outbreaks were caused by schoolchildren cases derived from within-household transmission. The frequency of 'school-household-school' transmission adds an additional layer of complexity to the control of school varicella outbreaks. Administration of varicella vaccine as post-exposure prophylaxis after exposure is considered to be an effective measure to control varicella spread within households and schools.
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Varicela/epidemiología , Varicela/transmisión , Brotes de Enfermedades , Instituciones Académicas , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Composición Familiar , Femenino , Humanos , Lactante , Masculino , Adulto JovenRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening monogenetic diseases characterized by progressive enlargement of fluid-filled renal cysts. Our previous study has shown that Ganoderma triterpenes (GT) retards PKD renal cyst development. In the present study we identified the effective ingredient of GT in suppression of kidney cyst development. Using an in vitro MDCK cystogenesis model, we identified ganoderic acid A (GA-A) as the most promising candidate among the 12 ganoderic acid (GA) monomers. We further showed that GA-A (6.25-100 µM) significantly inhibited cyst growth in MDCK cyst model and embryonic kidney cyst model in vitro, and the inhibitory effect was reversible. In kidney-specific Pkd1 knockout (kPKD) mice displaying severe cystic kidney disease, administration of GA-A (50 mg· kg-1 ·d-1, sc) significantly attenuated renal cyst development. In both MDCK cells and kidney of kPKD mice, we revealed that GA-A dose-dependently downregulated the Ras/MAPK signaling pathway. The expression of proliferating cell nuclear antigen (PCNA) was also suppressed, suggesting a possible effect of GA-A on cell proliferation. These experimental data suggest that GA-A may be the main ingredient of GT as a potential therapeutic reagent for treating ADPKD.
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Ganoderma/química , Ácidos Heptanoicos/farmacología , Lanosterol/análogos & derivados , Enfermedades Renales Poliquísticas/tratamiento farmacológico , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Ácidos Heptanoicos/administración & dosificación , Ácidos Heptanoicos/aislamiento & purificación , Inyecciones Subcutáneas , Lanosterol/administración & dosificación , Lanosterol/aislamiento & purificación , Lanosterol/farmacología , Células de Riñón Canino Madin Darby/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Enfermedades Renales Poliquísticas/patologíaRESUMEN
Renal fibrosis is considered as the pathway of almost all kinds of chronic kidney diseases (CKD) to the end stage of renal diseases (ESRD). Ganoderic acid (GA) is a group of lanostane triterpenes isolated from Ganoderma lucidum, which has shown a variety of pharmacological activities. In this study we investigated whether GA exerted antirenal fibrosis effect in a unilateral ureteral obstruction (UUO) mouse model. After UUO surgery, the mice were treated with GA (3.125, 12.5, and 50 mg· kg-1 ·d-1, ip) for 7 or 14 days. Then the mice were sacrificed for collecting blood and kidneys. We showed that GA treatment dose-dependently attenuated UUO-induced tubular injury and renal fibrosis; GA (50 mg· kg-1 ·d-1) significantly ameliorated renal disfunction during fibrosis progression. We further revealed that GA treatment inhibited the extracellular matrix (ECM) deposition in the kidney by suppressing the expression of fibronectin, mainly through hindering the over activation of TGF-ß/Smad signaling. On the other hand, GA treatment significantly decreased the expression of mesenchymal cell markers alpha-smooth muscle actin (α-SMA) and vimentin, and upregulated E-cadherin expression in the kidney, suggesting the suppression of tubular epithelial-mesenchymal transition (EMT) partially via inhibiting both TGF-ß/Smad and MAPK (ERK, JNK, p38) signaling pathways. The inhibitory effects of GA on TGF-ß/Smad and MAPK signaling pathways were confirmed in TGF-ß1-stimulated HK-2 cell model. GA-A, a GA monomer, was identified as a potent inhibitor on renal fibrosis in vitro. These data demonstrate that GA or GA-A might be developed as a potential therapeutic agent in the treatment of renal fibrosis.
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Proteínas Smad/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Triterpenos/farmacología , Obstrucción Ureteral/tratamiento farmacológico , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Inyecciones Intraperitoneales , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Triterpenos/administración & dosificación , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/cirugíaRESUMEN
Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner. ADAP2 functions as a GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and PI(3,4)P2. We show that overexpression of ADAP2 suppresses dengue virus (DENV) and vesicular stomatitis virus (VSV) infection in an Arf6 GAP activity-dependent manner, while exerting no effect on coxsackievirus B (CVB) or Sendai virus (SeV) replication. We further show that ADAP2 expression induces macropinocytosis and that ADAP2 strongly associates with actin-enriched membrane ruffles and with Rab8a- and LAMP1-, but not EEA1- or Rab7-, positive vesicles. Utilizing two techniques--light-sensitive neutral red (NR)-containing DENV and fluorescence assays for virus internalization--we show that ADAP2 primarily restricts DENV infection at the stage of virion entry and/or intracellular trafficking and that incoming DENV and VSV particles associate with ADAP2 during their entry. Taken together, this study identifies ADAP2 as an ISG that exerts antiviral effects against RNA viruses by altering Arf6-mediated trafficking to disrupt viral entry.
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Factores de Ribosilacion-ADP/agonistas , Virus del Dengue/fisiología , Proteínas Activadoras de GTPasa/agonistas , Interferón beta/metabolismo , Pinocitosis , Vesiculovirus/fisiología , Internalización del Virus , Factor 6 de Ribosilación del ADP , Factores de Ribosilacion-ADP/genética , Factores de Ribosilacion-ADP/metabolismo , Animales , Línea Celular , Chlorocebus aethiops , Virus del Dengue/inmunología , Enterovirus Humano B/inmunología , Enterovirus Humano B/fisiología , Proteínas Activadoras de GTPasa/genética , Proteínas Activadoras de GTPasa/metabolismo , Humanos , Mutación , Fosfatos de Fosfatidilinositol/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Virus Sendai/inmunología , Virus Sendai/fisiología , Células Vero , Vesiculovirus/inmunología , Virión/inmunología , Virión/fisiología , Replicación ViralRESUMEN
Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma.
Asunto(s)
Carcinoma Ductal Pancreático/patología , Factor 3 de Iniciación Eucariótica/metabolismo , Neoplasias Pancreáticas/patología , Anciano , Animales , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Factor 3 de Iniciación Eucariótica/antagonistas & inhibidores , Factor 3 de Iniciación Eucariótica/genética , Femenino , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Interferencia de ARN , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/metabolismo , Trasplante HeterólogoRESUMEN
INTRODUCTION: The efficacy of pressure-controlled volume-guaranteed ventilation (PCV-VG) combined with a gradient-directional change in positive end-expiratory pressure (PEEP) during one-lung ventilation (OLV) in patients who underwent thoracoscopic surgery was investigated. METHODS: Ninety patients were randomly divided into the PC (PCV-VG + 5 cm H2 O fixed PEEP), PI (PCV-VG + incremental PEEP titration), and PD (PCV-VG + decremental PEEP titration) groups. Hemodynamic (heart rate [HR] and mean arterial pressure [MAP]), respiratory mechanics (Ppeak , Pmean, and Cdyn), and arterial blood gas (pH, PaCO2 , PaO2 , and PaO2 /FiO2 ) indices were evaluated at T1 (10 min of two-lung ventilation [TLV]), T2 (10 min of OLV), and T3 (10 min of recovery, TLV). Enzyme-linked immunosorbent assay was performed to detect neutrophil elastase (NE), clara cell secretory protein (CC16), and interleukin-8 (IL-8) levels at T1 and T3. RESULTS: At T2 and T3 , Ppeak was lower in the PI and PD groups than in the PC group, while Pmean and Cdyn were higher than in the PC group. Ppeak in the PD group was lower than that in the PI group; however, Pmean was higher at T2 and T3 (P < 0.05). At T2 , PaO2 and PaO2 /FiO2 were higher, but PaO2 /FiO2 and VD /VT were lower in the PD and PI groups than in the PC group (P < 0.05). NE, CC16, IL-6, and IL-8 levels were elevated in all three groups at T3 , but the PI and PD groups had lower levels than the PC group (P < 0.05). The incidences of postoperative pulmonary complications (PPCs) and surgical intensive care unit hospitalizations in the PD and PI groups were much lower. CONCLUSION: Gradient-directed altered PEEP titration could improve respiratory mechanics, arterial blood gases, and inflammatory responses and reduce the incidence of PPCs in patients undergoing thoracoscopic surgery.
Asunto(s)
Interleucina-8 , Ventilación Unipulmonar , Humanos , Pulmón , Respiración con Presión Positiva , Ventilación con Presión Positiva IntermitenteRESUMEN
The development of smart protective clothing will help detect injuries from contact sports, traffic collisions, and other accidents. The combination of ecoflex, spacer fabric, and graphene-based aerogel provides a multifunctional composite. It shows a strain sensitivity of 17.71 at the strain range of 40~55%, a pressure sensitivity of 0.125 kPa-1 at the pressure range of 0~15 kPa, and a temperature sensitivity of -0.648 °C-1. After 50 impact tests, its protection coefficient only dropped from 60% to 55%. Additionally, it shows thermal insulation properties. The compression and impact process results of finite element numerical simulation analysis are in good agreement with the experimental results. The ecoflex/aerogel/spacer fabric sensor exhibits a simple structure, large pressure strain, high sensitivity, flexibility, and ease of fabrication, making it a candidate for smart protective clothing resistant to impact loads.