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Although recent studies on blind single image super-resolution (SISR) have achieved significant success, most of them typically require supervised training on synthetic low resolution (LR)-high resolution (HR) paired images. This leads to re-training necessity for different degradations and restricted applications in real-world scenarios with unfavorable inputs. In this paper, we propose an unsupervised blind SISR method with input underlying different degradations, named different degradations blind super-resolution (DDSR). It formulates a Gaussian modeling on blur degradation and employs a meta-learning framework for solving different image degradations. Specifically, a neural network-based kernel generator is optimized by learning from random kernel samples, referred to as random kernel learning. This operation provides effective initialization for blur degradation optimization. At the same time, a meta-learning framework is proposed to resolve multiple degradation modelings on the basis of alternative optimization between blur degradation and image restoration, respectively. Differing from the pre-trained deep-learning methods, the proposed DDSR is implemented in a plug-and-play manner, and is capable of restoring HR image from unfavorable LR input with degradations such as partial coverage, noise addition, and darkening. Extensive simulations illustrate the superior performance of the proposed DDSR approach compared to the state-of-the-arts on public datasets with comparable memory load and time consumption, yet exhibiting better application flexibility and convenience, and significantly better generalization ability towards multiple degradations. Our code is available at https://github.com/XYLGroup/DDSR.
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Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodos , Humanos , Aprendizaje Profundo , Algoritmos , Simulación por Computador , Aprendizaje AutomáticoRESUMEN
Learning based approaches have witnessed great successes in blind single image super-resolution (SISR) tasks, however, handcrafted kernel priors and learning based kernel priors are typically required. In this paper, we propose a Meta-learning and Markov Chain Monte Carlo based SISR approach to learn kernel priors from organized randomness. In concrete, a lightweight network is adopted as kernel generator, and is optimized via learning from the MCMC simulation on random Gaussian distributions. This procedure provides an approximation for the rational blur kernel, and introduces a network-level Langevin dynamics into SISR optimization processes, which contributes to preventing bad local optimal solutions for kernel estimation. Meanwhile, a meta-learning based alternating optimization procedure is proposed to optimize the kernel generator and image restorer, respectively. In contrast to the conventional alternating minimization strategy, a meta-learning based framework is applied to learn an adaptive optimization strategy, which is less-greedy and results in better convergence performance. These two procedures are iteratively processed in a plug-and-play fashion, for the first time, realizing a learning-based but plug-and-play blind SISR solution in unsupervised inference. Extensive simulations demonstrate the superior performance and generalization ability of the proposed approach when comparing with state-of-the-arts on synthesis and real-world datasets.
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BACKGROUND: The tumor microenvironment (TME) has recently been proven to play a crucial role in the development and prognosis of tumors. However, the current knowledge on the potential of the TME in prostate cancer (PCa) remains scarce. PURPOSE: This study aims to elucidate the value of TME-related genes for PCa prognosis by integrative bioinformatics analysis. MATERIALS AND METHODS: We downloaded the immune and stromal scores of PCa samples via the ESTIMATE and correlated these scores to clinicopathological characteristics and recurrence-free survival (RFS) of patients. Based on these scores, the TME-related differentially expressed genes were identified for functional enrichment analysis. Cox regression analyses were performed to identify prognostic genes and establish a predictive risk model. Moreover, gene set enrichment analysis (GSEA) was performed to evaluate the relationship between risk score and immune pathway. RESULTS: The stromal and immune scores were associated with clinicopathological characteristics and RFS in PCa patients. In total, 238 intersecting differentially expressed genes were identified. Functional enrichment analysis further revealed that these genes dramatically participated in the immune-related pathways. The immune-related risk model was built with C-type lectin domain containing 7A (CLEC7A) and collagen type XI alpha 1 chain (COL11A1) using Cox regression analyses. Kaplan-Meier survival analysis showed that the expression levels of CLEC7A and COL11A1 were significantly associated with the RFS. Further, the RFS time in high-risk group was significantly shorter than that in low-risk group. The areas under the curve for the risk model in predicting 3- and 5-year RFS rates were 0.694 and 0.731, respectively. GSEA suggested that immunosuppression existed in high-risk PCa patients. CONCLUSION: CLEC7A and COL11A1 were selected to build a predictive risk model, which may help clinicians to assess the prognosis of PCa patients and select appropriate targets for immunotherapy.
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BACKGROUND: Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. METHODS: This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. RESULTS: The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. CONCLUSIONS: Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.
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Funcionamiento Retardado del Injerto/etiología , Trasplante de Riñón/efectos adversos , Donantes de Tejidos/estadística & datos numéricos , Adulto , Muerte Encefálica , China , Isquemia Fría/efectos adversos , Creatinina/análisis , Funcionamiento Retardado del Injerto/terapia , Femenino , Supervivencia de Injerto , Humanos , Incidencia , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Curva ROC , Diálisis Renal/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo , Trasplantes/fisiopatologíaRESUMEN
BACKGROUND The aim of this study was to investigate the efficacy and safety of right retroperitoneal laparoscopic live donor nephrectomy (LDN) in 81 cases of living-related renal transplant. MATERIAL AND METHODS We retrospectively reviewed all living-related donors who underwent right retroperitoneoscopic living donor nephrectomy between June 2010 and December 2017 at the First Hospital of Jilin University and their corresponding recipients. Demographic and clinical data were collected from the hospital's electronic clinical data system. Data on preoperative renal retention parameters, operative time, and donor kidney warm ischemia time, the trimmed length of the renal artery and vein of donor kidney, and the time to extubation were recorded. Complications in both donors and recipients were recorded. RESULTS We included 81 donors who underwent successful right-sided retroperitoneoscopic LDN, with 31 males and 50 females and a mean age of 47.1 years (range 21-63 years). There was no intraoperative conversion to open donor nephrectomy. The mean operative time was 120.68±29.8 min. The mean warm ischemic time was 49.26±3.86 s. The estimate blood loss was 54.32 mL (range 50-400 mL). The median length of hospital stay was 7 days (range 4-13 days). There was neither intraoperative complication such as hemorrhage or lymph fistula nor kidney graft injury. There was no graft renal vein thrombosis and ureteral stricture or other complications. No graft rejection occurred. CONCLUSIONS Right retroperitoneal laparoscopic live donor nephrectomy is safe and effective for renal transplant in living-related renal transplant by laparoscopic excision and extraction of the right kidney with vena cava flap.
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Trasplante de Riñón/efectos adversos , Laparoscopía/efectos adversos , Donadores Vivos , Nefrectomía/efectos adversos , Recolección de Tejidos y Órganos/efectos adversos , Adulto , Femenino , Humanos , Riñón/irrigación sanguínea , Trasplante de Riñón/métodos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , Estudios Retrospectivos , Recolección de Tejidos y Órganos/métodos , Resultado del Tratamiento , Isquemia Tibia , Adulto JovenRESUMEN
Hyperglycemia-induced renal fibrosis causes end-stage renal disease. Clopidogrel, a platelet inhibitor, is often administered to decrease cardiovascular events in diabetic patients. We investigated whether clopidogrel can reduce diabetes-induced renal fibrosis in a streptozotocin-induced type 1 diabetes murine model and fibronectin involvement in this protective response. Diabetic and age-matched controls were sacrificed three months after the onset of diabetes, and additional controls and diabetic animals were further treated with clopidogrel or vehicle for three months. Diabetes induced renal morphological changes and fibrosis after three months. Clopidogrel, administered during the last three months, significantly decreased blood glucose, collagen and fibronectin expression compared to vehicle-treated diabetic mice. Diabetes increased TGF-ß expression, inducing fibrosis via Smad-independent pathways, MAP kinases, and Akt activation at three months but returned to baseline at six months, whereas the expression of fibronectin and collagen remained elevated. Our results suggest that activation of TGF-ß, CTGF, and MAP kinases are early profibrotic signaling events, resulting in significant fibronectin accumulation at the early time point and returning to baseline at a later time point. Akt activation at the three-month time point may serve as an adaptive response in T1D. Mechanisms of clopidogrel therapeutic effect on the diabetic kidney remain to be investigated as this clinically approved compound could provide novel approaches to prevent diabetes-induced renal disease, therefore improving patients' survival.
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Clopidogrel/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Fibronectinas/metabolismo , Fibrosis/tratamiento farmacológico , Fibrosis/etiología , Enfermedades Renales/tratamiento farmacológico , Animales , Coagulación Sanguínea/efectos de los fármacos , Western Blotting , Clopidogrel/farmacología , Fibrosis/metabolismo , Inmunohistoquímica , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Antagonistas del Receptor Purinérgico P2Y/farmacología , Antagonistas del Receptor Purinérgico P2Y/uso terapéuticoRESUMEN
BACKGROUND/AIM: Glioma is a deadly form of brain cancer. Doxorubicin is cytotoxic against glioma cells. However, the blood-brain barrier (BBB) limits its ability to be delivered to the brain. MATERIALS AND METHODS: Liposomes (R8PLP) formed from, 1,2-dioleoyl-3-trimethylammonium-propane chloride (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000] (PEG-DSPE), cholesterol and egg phosphatidylcholine (ePC) were modified by cell-penetrating peptide R8 conjugated with oleic acid as a novel method for delivering doxorubicin. The antitumor effect of R8PLP was evaluated by uptake, cytotoxicity and brain accumulation. RESULTS: The size of R8PLP was 95 nm. Doxorubicin was loaded into R8PLP by active loading with more than 95% encapsulation efficiency. Cellular uptake of R8PLP by U87-MG cells was 8.6-fold higher than that of unmodified liposomes. R8PLP reduced cell viability by 16.18% and 18.11% compared to cholesterol-ePC-liposomes and free doxorubicin, respectively, at 3.6 µM after 24 h treatment. The biodistribution of doxorubicin in the brain was significantly improved by R8PLP. The area under the concentration-time curve (AUC0.5-12 h) of R8PLP was 2.4-times higher than that of cholesterol-ePC-PEG-DSPE-liposomes. CONCLUSION: These results suggest that R8-conjugated oleic acid-modified liposomes are effective delivery vehicles for glioma.
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Péptidos de Penetración Celular/administración & dosificación , Sistemas de Liberación de Medicamentos , Glioma/tratamiento farmacológico , Nanopartículas/administración & dosificación , Barrera Hematoencefálica/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Péptidos de Penetración Celular/química , Colesterol/química , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Ácidos Grasos Monoinsaturados/química , Glioma/patología , Humanos , Liposomas/administración & dosificación , Liposomas/química , Nanopartículas/química , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenglicoles/química , Compuestos de Amonio Cuaternario/química , Distribución Tisular/efectos de los fármacosRESUMEN
CD47 is a ubiquitously expressed transmembrane glycoprotein that plays a complex role in regulation of cell survival and function. We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of cellular xenografts by macrophages. However, the role of CD47 in solid organ transplantation remains undetermined. Here, we explored this question in mouse models of heart allotransplantation. We observed that the lack of CD47 in donor hearts had no deleterious effect on graft survival in syngeneic or single MHC class I-mismatched recipients, in which both wild-type (WT) and CD47 knockout (CD47 KO) mouse hearts survived long term with no sign of rejection. Paradoxically, elimination of donor CD47 was beneficial for graft survival in signal MHC class II- and class I- plus class II-mismatched combinations, in which CD47 KO donor hearts showed significantly improved survival compared to WT donor hearts. Similarly, CD47 KO donor hearts were more resistant than WT hearts to humoral rejection in α1,3-galactosyltransferase-deficient mice. Moreover, a significant prolongation of WT allografts was observed in recipient mice treated with antibodies against a CD47 ligand thrombospondin-1 (TSP1) or with TSP1 deficiency, indicating that TSP1-CD47 signaling may stimulate vascularized allograft rejection. Thus, unlike cellular transplantation, donor CD47 expression may accelerate the rejection of vascularized allografts.
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Aloinjertos/inmunología , Antígeno CD47/inmunología , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Trombospondina 1/inmunología , Animales , Antígeno CD47/genética , Trasplante de Células/métodos , Rechazo de Injerto/genética , Supervivencia de Injerto/genética , Trasplante de Corazón/métodos , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Trombospondina 1/genética , Trasplante Heterólogo/métodos , Trasplante Homólogo/métodosRESUMEN
In real applications, the image quality of the conventional monostatic Inverse Synthetic Aperture Radar (ISAR) for the maneuvering target is subject to the strong fluctuation of Radar Cross Section (RCS), as the target aspect varies enormously. Meanwhile, the maneuvering target introduces nonuniform rotation after translation motion compensation which degrades the imaging performance of the conventional Fourier Transform (FT)-based method in the cross-range dimension. In this paper, a method which combines the distributed ISAR technique and the Matching Fourier Transform (MFT) is proposed to overcome these problems. Firstly, according to the characteristics of the distributed ISAR, the multiple channel echoes of the nonuniform rotation target from different observation angles can be acquired. Then, by applying the MFT to the echo of each channel, the defocused problem of nonuniform rotation target which is inevitable by using the FT-based imaging method can be avoided. Finally, after preprocessing, scaling and rotation of all subimages, the noncoherent fusion image containing all the RCS information in all channels can be obtained. The accumulation coefficients of all subimages are calculated adaptively according to the their image qualities. Simulation and experimental data are used to validate the effectiveness of the proposed approach, and fusion image with improved recognizability can be obtained. Therefore, by using the distributed ISAR technique and MFT, subimages of high-maneuvering target from different observation angles can be obtained. Meanwhile, by employing the adaptive subimage fusion method, the RCS fluctuation can be alleviated and more recognizable final image can be obtained.
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Cancer is a leading cause of death throughout the world, and cancer therapy remains a big medical challenge in terms of both its therapeutic efficacy and safety. Therefore, to find out a safe anticancer drug has been long goal for oncologist and medical scientists. Among clinically used medicines with no or little toxicity, fenofibrate is a drug of the fibrate class that plays an important role in lowering the levels of serum cholesterol and triglycerides while elevating the levels of high-density lipoproteins. Recently, several studies have implied that fenofibrate may exert anticancer effects via a variety of pathways involved in apoptosis, cell-cycle arrest, invasion, and migration. Given the great potential that fenofibrate may have anticancer effects, this review was to investigate all published works which directly or indirectly support the anticancer activity of fenofibrate. These studies provide evidence that fenofibrate exerted antitumor effects in several human cancer cell lines, such as breast, liver, glioma, prostate, pancreas, and lung cancer cell lines. Among these studies some have further confirmed the possibility and efficacy of fenofibrate anticancer in xenograft mouse models. In the last part of this review, we also discuss the potential mechanisms of action of fenofibrate based on the available information. Overall, we may repurpose fenofibrate as an anticancer drug in cancer treatment, which urgently need further and comprehensively investigated.
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Primary hyperoxaluria type 2 is a rare autosomal recessive disorder caused by glyoxylate reductase/hydroxypyruvate reductase deficiency and characterized by recurrent episodes of nephrolithiasis and nephrocalcinosis. Herein, we describe a case of primary hyperoxaluria type 2 in a 33-year-old man who failed to respond to conventional therapies; thus renal transplantation was performed. This case demonstrated that, although primary hyperoxaluria type 2 is rare, hyperoxaluria should be suspected and blood oxalate and stone component be examined in patients with recurrent episodes of nephrolithiasis, particularly in those who are unresponsive to conventional therapies. Combined liver-kidney transplant may be required as kidney transplant alone is not likely to be successful.
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BACKGROUND: Though many studies have been performed to elucidate the association between circulating vitamin D and prostate cancer, no conclusive result is available. We carried out a dose-response meta-analysis to quantitatively examine the association of circulating 25-hydroxyvitamin D (25[OH]D) concentration with prostate cancer. METHODS: Only prospective studies examining the associations of circulating 25[OH]D concentration with prostate cancer were eligible for the meta-analysis. A random-effect meta-analysis was done first, to calculate the summary relative risk (RR) and 95% confidence intervals (CIs) comparing the higher concentration with the lower concentration of 25[OH]D. A dose-response meta-analysis using random-effects model was then carried out to evaluate the nonlinearity and calculate the summary RR caused per 10 ng/mL increment. RESULTS: Nineteen prospective cohort or nested case-control studies were included. Higher 25[OH]D concentration was significantly correlated with elevated risk of prostate cancer (RR =1.15, 95% CI 1.06-1.24). No nonlinear relationship was found between 25[OH]D concentration and risk of prostate cancer (P=0.654). Dose-response meta-analysis showed that the summary RR caused per 10 ng/mL increment in circulating 25[OH]D concentration was 1.04 (95% CI 1.02-1.06). Subgroup analysis also found a modest dose-response relationship. Funnel plot and Egger's test did not detect publication bias. CONCLUSION: The findings suggest that highest 25[OH]D concentration is correlated with elevated risk of prostate cancer and a modest dose-response effect exists in this association; however, more studies are needed.
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Zinc is one of the essential trace elements and participates in numerous physiological processes. Abnormalities in zinc homeostasis often result in the pathogenesis of various chronic metabolic disorders, such as diabetes and its complications. Zinc has insulin-mimetic and anti-diabetic effects and deficiency has been shown to aggravate diabetes-induced oxidative stress and tissue injury in diabetic rodent models and human subjects with diabetes. Akt signaling pathway plays a central role in insulin-stimulated glucose metabolism and cell survival. Anti-diabetic effects of zinc are largely dependent on the activation of Akt signaling. Zn is also an inducer of metallothionein that plays important role in anti-oxidative stress and damage. However, the exact molecular mechanisms underlying zinc-induced activation of Akt signaling pathway remains to be elucidated. This review summarizes the recent advances in deciphering the possible mechanisms of zinc on Akt-mediated insulin and cell survival signaling pathways in diabetes conditions. Insights into the effects of zinc on epigenetic regulation and autophagy in diabetic nephropathy are also discussed in the latter part of this review.
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Diabetes Mellitus/metabolismo , Insulina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Oligoelementos/metabolismo , Zinc/metabolismo , Animales , Autofagia , Supervivencia Celular , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/patología , Epigénesis Genética , Glucosa/metabolismo , Humanos , Metalotioneína/metabolismo , Estrés Oxidativo , Transducción de Señal , Oligoelementos/deficiencia , Zinc/deficienciaRESUMEN
BACKGROUND: The objective of this study was to examine the effectiveness and safety of lower pole (LP) approach in retroperitoneal laparoscopic radical nephrectomy (LRN). METHODS: One hundred thirty-two renal cancer patients were scheduled for selective retroperitoneal LRN. The surgery parameters and outcomes were compared. Out of 132 patients, 78 (59.1%) patients underwent LRN via LP approach, while 54 (40.9%) patients underwent LRN via lateroposterior space (LPS) approach. RESULTS: Compared to LPS group, the LP group had a higher body mass index (27.0 ± 1.7 kg/m2 vs. 24.5 ± 1.8 kg/m2, P < 0.0001) and a larger tumor size (6.9 ± 3.5 cm vs. 4.1 ± 3.3 cm, P < 0.0001). The LP approach reduced the volumes of blood loss and transfusion significantly (135.3 ± 17.2 mL vs. 219.6 ± 30.9 mL, P < 0.0001; 55.6 ± 28.3 vs. 141.1 ± 50.4 mL, P < 0.0001) as compared to the LPS approach. The LP approach also decreased the risk of conversion to open procedure (1.3 vs. 7.4%, P < 0.05). CONCLUSIONS: The LP approach is an effective and safe alternative to the LPS approach for retroperitoneal LRN and might be more suitable for patients with obesity, large tumors, tumors located at the medial part of the kidney, or renal pedicular adhesion.
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Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Laparoscopía/métodos , Nefrectomía/métodos , Espacio Retroperitoneal/cirugía , Carcinoma de Células Renales/irrigación sanguínea , Carcinoma de Células Renales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Espacio Retroperitoneal/irrigación sanguínea , Espacio Retroperitoneal/patología , Estudios RetrospectivosRESUMEN
Fenofibrate is the most widely used lipid-lowering drug, but it seems to have anti-tumor effects in several tumor cell lines. However, there are only a few reports on its effects on human prostate cancer cells. Thus, we investigated the anti-proliferative effects of fenofibrate on human prostate cancer cells and potential mechanisms. The methods used include cell viability analysis with an MTT assay, as well as apoptosis and related signaling pathway analyses with flow cytometry and Western blotting. Fenofibrate inhibited PC-3â¯cell growth in dose- and time-dependent manners. The fenofibrate-induced cell death is predominantly apoptotic death that is mediated by both the caspase-3 activation and apoptosis-inducing factor (AIF) signaling pathways. Fenofibrate also increased the expression of Bad and decreased the expression of Bcl-2 and Survivin. Mechanistically, fenofibrate-induced cell death was associated with decreased p-p70S6K and the mammalian target of rapamycin (mTOR) phosphorylation levels. When further exploring the upstream mediators of mTOR/p70S6K, we found that fenofibrate increased p38 MAPK and AMPK phosphorylation but did not significantly change the phosphorylation levels of PI3K, AKT, and JNK. However, the inhibition of either p38 MAPK or AMPK with their specific inhibitor did not change the effect of fenofibrate-induced cell death. These findings suggested that fenofibrate indeed significantly inhibited the proliferation of PC-3â¯cells via apoptotic action, which is associated with the inactivation of the mTOR/p70S6K-dependent cell survival pathway. Although the mechanisms by which fenofibrate inactivates this pathway remains unclear, this study reveals great potential for its use for the clinical treatment of prostate cancers.
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Apoptosis/efectos de los fármacos , Fenofibrato/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Humanos , Masculino , Terapia Molecular Dirigida/métodos , Neoplasias de la Próstata/patología , Transducción de Señal/efectos de los fármacosRESUMEN
Objective To investigate the effect of diabetes with and without vitamin E treatment on testicular metallothionein (MT) and metal (zinc, copper and iron) changes. Methods Diabetes was induced with a single intraperitoneal injection (i.p.) of streptozotocin in rats, and diabetic rats were given Vitamin E by i.p. every other day for 4 weeks. MT protein was measured by the cadmium-haeme assay and metal levels were detected by an atomic absorption spectrophotometer. Results Diabetes did not change testicular MT protein, but significantly increased hepatic MT protein. Diabetes significantly decreased testicular copper, but not hepatic copper. Zinc and iron levels were unchanged in both diabetic testis and liver. Vitamin E significantly enhanced both testicular and hepatic MT, and zinc levels in diabetic rats. Vitamin E slightly decreased the copper levels, but did not change the testicular and hepatic iron in diabetic rats. Conclusions Testicular MT protein expression was not increased, even though hepatic MT significantly increased independent of metal changes, in diabetic rats. Vitamin E enhanced testicular and hepatic MT, which correlated with increased zinc levels.
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Diabetes Mellitus Experimental/genética , Hígado/metabolismo , Metalotioneína/genética , ARN Mensajero/genética , Testículo/metabolismo , Vitamina E/farmacología , Animales , Glucemia/metabolismo , Cobre/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Experimental/patología , Expresión Génica , Inyecciones Intraperitoneales , Hierro/metabolismo , Hígado/efectos de los fármacos , Masculino , Metalotioneína/metabolismo , Especificidad de Órganos , Estrés Oxidativo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Estreptozocina , Testículo/efectos de los fármacos , Zinc/metabolismoRESUMEN
BACKGROUND: Previous studies identified B cell gene signatures and predominance of specific B cell subsets as a marker of operational tolerance after kidney transplantation. These findings suggested a role for B cells in the establishment or maintenance of tolerance. Here we analyzed B cell recovery in 4 subjects, 3 of whom achieved tolerance after combined kidney/bone marrow transplantation. METHODS: Peripheral B cell subsets were examined longitudinally by flow cytometry. Immunoglobulin heavy chain repertoire analysis was performed using next-generation sequencing. Lastly, the patients' serum reactivity to HLA was assessed by Luminex. RESULTS: B cell counts recovered approximately 1 year posttransplant except for 1 subject who experienced delayed reconstitution. This subject resumed immunosuppression for acute rejection at 10 months posttransplant and underwent preemptive retransplantation at 3 years for chronic rejection. B cell recovery was accompanied by a high frequency of CD20 + CD24CD38 transitional B cells and a diversified clonal repertoire. However, all 4 subjects showed prevalence of CD20 + CD27+ memory B cells around 6 months posttransplant when B cell counts were still low and the clonal B cell repertoire very limited. The predominance of memory B cells was also associated with high levels of somatically mutated immunoglobulin heavy chain variable sequences and transient serum reactivity to HLA. CONCLUSIONS: Our observations reveal the presence of memory B cells early posttransplant that likely escaped the preparative regimen at a time consistent with the establishment of tolerance. Further studies are warranted to characterize the functional properties of these persisting memory cells and evaluate their potential contribution to tolerance induction.
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Linfocitos B/inmunología , Trasplante de Médula Ósea , Proliferación Celular , Trasplante de Riñón , Linfocitos B/metabolismo , Biomarcadores/sangre , Boston , Femenino , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Supervivencia de Injerto , Antígenos HLA/inmunología , Hospitales Generales , Humanos , Memoria Inmunológica , Isoanticuerpos/sangre , Recuento de Linfocitos , Masculino , Mutación , Fenotipo , Recuperación de la Función , Factores de Tiempo , Tolerancia al Trasplante , Resultado del TratamientoRESUMEN
AIM: A wealth of studies have demonstrated that abnormal cellular lipid metabolism plays an important role in prostate cancer (PCa) development. Therefore, manipulating lipid metabolism is a potential PCa therapy strategy. In this study, our goal is to investigate the role of farnesoid X receptor (FXR) in regulating the proliferation and lipid metabolism of human PCa cells following its ligand chenodexycholic acid (CDCA) treatment. METHODS: Oil Red O was used to stain lipid contents in PCa cells, and siRNA knockdown was performed to deplete FXR expression. To study the cell proliferation when treated by CDCA or FXR knockdown, cell counting kit 8 (CCK8) was adopted to evaluate tumor cell growth. Western blot was used for protein analysis. RESULTS: Our data suggest that activation of FXR by CDCA reduces lipid accumulation and significantly inhibits cells proliferation in prostate tumor cells. Instead, CDCA treatment doesn't affect normal prostate epithelial RWPE-1 cells growth in vitro. FXR activation decreases mRNA and protein levels of sterol regulatory element binding protein 1 (SREBP1) and some other key regulators involved in lipid metabolism. Depletion of FXR by siRNA attenuates the inhibitory effects. CONCLUSION: Our study indicates that activation of FXR inhibits lipid metabolism via SREBP1 pathway and further suppresses prostate tumor growth in vitro.
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BACKGROUND: The aim of this study was to evaluate the efficacy of preoperative intravenous oxycodone administration on postoperative sufentanil consumption in patients undergoing retroperitoneal laparoscopic nephrectomy. METHODS: Fifty patients scheduled for retroperitoneal laparoscopic nephrectomy were enrolled and randomly assigned to two groups- patients in Group O (n = 25) received intravenously 0.1 mg kg⻹ oxycodone; while the patients in Group C (n = 25) received 0.1 mL kg⻹ normal saline for 2 min, 10 min before the operation. All of the participants received intravenous sufentanil patient-controlled analgesia (PCA) after extubation, using a PCA device. The sufentanil consumption, rescue analgesia, Ramsay sedation scale (RSS) and visual analogue scale (VAS) scores at rest and during cough, the overall satisfaction and undesired events were all assessed. RESULTS: Cumulative sufentanil consumption delivered by PCA was significantly lower in Group O at all time points. VAS scores at rest and during coughing at 1, 2, 4, 8 and 12 hours after extubation of the patient were significantly lower in Group O than in Group C. There were no significant differences between the two groups according to the number of patients administered tramadol, RSS and the incidence of side effects. The degree of patients' satisfaction was higher in Group O. CONCLUSION: Preoperative intravenous oxycodone can reduce postoperative cumulative sufentanil consumption and postoperative pain intensity without an increase in side effects.
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Analgésicos Opioides/uso terapéutico , Laparoscopía/métodos , Nefrectomía/métodos , Oxicodona/uso terapéutico , Dolor Postoperatorio/prevención & control , Cuidados Preoperatorios/métodos , Sufentanilo/uso terapéutico , Adulto , Anciano , Analgesia Controlada por el Paciente , Analgésicos Opioides/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Oxicodona/administración & dosificación , Dimensión del Dolor , Satisfacción del Paciente , Sufentanilo/administración & dosificación , Tramadol/uso terapéuticoRESUMEN
OBJECTIVE: To compare caudal block with intrarectal local anesthesia plus periprostatic nerve block for transrectal ultrasound guided prostate biopsy. METHODS: One hundred and ninety patients scheduled for transrectal ultrasound guided prostate biopsy were randomized equally into Group-A who received caudal block (20 ml 1.2% lidocaine) and Group-B who received intrarectal local anesthesia (0.3% oxybuprocaine cream) plus periprostatic nerve block (10 ml 1% lidocaine plus 0.5% ropivacaine) before biopsy. During and after the procedure, the patients rated the level of pain/discomfort at various time points. Complications during the whole study period and the patient overall satisfaction were also evaluated. RESULTS: More pain and discomfort was detected during periprostatic nerve block than during caudal block. Pain and discomfort was significantly lower during prostate biopsy and during the manipulation of the probe in the rectum in Group-A than in Group-B. No significant differences were detected in the pain intensity after biopsy and side effects between the two groups. CONCLUSIONS: Caudal block provides better anesthesia than periprostatic nerve block plus intrarectal local anesthesia for TRUS guided prostate biopsy without an increase of side effects.