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关键词： Diffuse large B-cell lymphoma   Epigenetics   EZH2-target genes   Exosome  

摘要： Aims Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma. This study was designed to compare epigenetic alterations observed in Enhancer of Zeste Homolog 2 (EZH2)-target genes between plasma-derived exosomes and primary tumors in DLBCL patients. Main methods Exosomes were isolated from plasma of 21 DLBCL patients and 21 controls. We analyzed the methylation status of the target genes using methylation-specific PCR. We also examined whether the exosomes and the tumor samples contained transcripts of the target genes. Key findings We found that CDKN2A and CDKN2B were methylated in both plasma exosomes and primary tumor tissue samples. None of the transcripts were found in the exosomes except CDKN1B which was expressed in 8 (38%) of the exosome samples. Significance This study showed that plasma exosomes might preferably package certain target molecules from primary tumors and the exosomes containing dual methylated DNAs of CDKN2A and CDKN2B, or CDKN1B transcript may contribute to DLBCL pathogenesis.

关键词： NMRT   osteoarthritis   miR   MMPs   inflammation  

摘要： Nuclear magnetic resonance therapy (NMRT) is discussed as a participant in repair processes regarding cartilage and as an influence in pain signaling. To substantiate the application of NMRT, the underlying mechanisms at the cellular level were studied. In this study microRNA (miR) was extracted from human primary healthy and osteoarthritis (OA) chondrocytes after NMR treatment and was sequenced by the Ion PI Hi-Q (TM) Sequencing 200 system. In addition, T/C-28a2 chondrocytes grown under hypoxic conditions were studied for IL-1 beta induced changes in expression on RNA and protein level. HDAC activity an NAD((+))/NADH was measured by luminescence detection. In OA chondrocytes miR-106a, miR-27a, miR-34b, miR-365a and miR-424 were downregulated. This downregulation was reversed by NMRT. miR-365a-5p is known to directly target HDAC and NF-kappa B, and a decrease in HDAC activity by NMRT was detected. NAD(+)/NADH was reduced by NMR treatment in OA chondrocytes. Under hypoxic conditions NMRT changed the expression profile of HIF1, HIF2, IGF2, MMP3, MMP13, and RUNX1. We conclude that NMRT changes the miR profile and modulates the HDAC and the NAD((+))/NADH signaling in human chondrocytes. These findings underline once more that NMRT counteracts IL-1 beta induced changes by reducing catabolic effects, thereby decreasing inflammatory mechanisms under OA by changing NF-kappa B signaling.

关键词： Preeclampsia   Nicotinamide   sFlt-1   Soluble endoglin   Placenta  

摘要： Preeclampsia is a serious pregnancy complication associated with elevated antiangiogenic markers and endothelial dysfunction. Recently nicotinamide (vitamin B3) was shown to reduce high blood pressure and proteinuria in mice models of the disease. Using primary human pregnancy tissue we show nicotinamide did not change antiangiogenic factor secretion including soluble fms-like tyrosine kinase 1 or soluble endoglin from primary cytotrophoblasts and placental explants. Furthermore, it did not reverse markers of endothelial dysfunction. Therefore, we did not demonstrate an effect of nicotinamide on reducing markers of preeclampsia from primary human placental tissues and vascular cells.

关键词： Scattering   Image classification   Feature extraction   Deep learning   Speckle   Entropy   Data models   Bayesian information fusion   complex-valued 3D-convolutional neural network (C3NN)   conditional random fields (CRFs)   deep learning model   polarimetric synthetic aperture radar (PolSAR) image classification   relative entropy (RE)  

摘要： In this article, we propose a hybrid conditional random field model based on complex-valued 3-D convolutional neural network (C3NN), named as HCRF-C3NN, for polarimetric synthetic aperture radar (PolSAR) image classification. HCRF-C3NN combines the modeling power of random fields with the representation-learning ability of deep learning model for PolSAR image. By C3NN, HCRF-C3NN exploits deep amplitude and phase information of PolSAR data and, thus, measures the class probabilities in the framework of random fields. Additionally, HCRF-C3NN captures the spatial label interactions effectively in PolSAR image classification by the following work: 1) Based on the C3NN-based class probabilities, the relative entropy of class distributions is derived to describe the local structure and, thus, regulates the pairwise label interactions, which enhances the accuracy of edge location in the classification;2) a product-of-expert potential is introduced to enforce label consistency, and, thus, HCRF-C3NN is more robust against speckle of PolSAR image and achieves smoother classification within the consistent class region. At last, to capture PolSAR image information in a more complete manner, the deep features and PolSAR scattering statistics are integrated into HCRF-C3NN based on Bayesian fusion. In this way, HCRF-C3NN effectively explores spatial correlation, scattering statistics, and deep features of PolSAR data in the framework of random fields. The experimental results demonstrate the superiority of HCRF-C3NN over the recent deep learning models for PolSAR image classification.

关键词： Malignant neoplasm   Primary intraosseous squamous cell carcinoma   Clinicopathological feature   Prognosis  

摘要： Primary intraosseous oral squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that affects the jaws. Despite its aggressive biological behavior, there are no studies that evaluated the clinicopathological features of this tumor and parameters associated with its prognosis. The objective of the present study was to conduct a systematic review of the available data on oral and maxillofacial PIOSCC in order to determine its clinicopathological characteristics and biological behavior. We conducted a systematic review in May 2020 in multiple databases using a specific search strategy. Cases diagnosed as PIOSCC in the oral cavity and maxillofacial complex that had sufficient histopathological data, absence of ulceration in the oral mucosa, a negative result for a distant primary tumor, and radiographic evidence of an osteolytic lesion that was entirely or mostly surrounded by the jaw bones were included. A total of 109 published articles were included in our systematic review, corresponding to 257 cases. PIOSCC showed a male predilection (69.3%) and a preference for the mandible (7:1), with the posterior region being the most commonly affected site. The mean age at diagnosis was 57.3 years. Cortical expansion, pain, and lip/facial paresthesia were the most common clinical features. Regarding histopathological features, most PIOSCC were well-differentiated and the solid subtype was the most common. Statistical analysis showed that PIOSCC located in the mandible (p = 0.03) and recurrence (p < 0.01) were significantly associated with a higher mortality rate. PIOSCC has a poor prognosis, with high rates of mortality.

关键词： cartilage   digital image analysis   live-cell imaging   osteoarthritis   phase-contrast imaging   stem and progenitor cells  

摘要： Reliable and reproducible cell therapy strategies to treat osteoarthritis demand an improved characterization of the cell and heterogeneous cell population resident in native cartilage tissue. Using live-cell phase-contrast time-lapse imaging (PC-TLI), this study investigates the morphological attributes and biological performance of the three primary biological objects enzymatically isolated from primary human cartilage: connective tissue progeni-tors (CTPs), non-progenitors (NPs) and multi-cellular structures (MCSs). The authors' results demonstrated that CTPs were smaller in size in comparison to NPs (P < 0.001). NPs remained part of the adhered cell population throughout the cell culture period. Both NPs and CTP progeny on day 8 increased in size and decreased in circu-larity in comparison to their counterparts on day 1, although the percent change was considerably less in CTP progeny (P < 0.001). PC-TLI analyses indicated three colony types: single-CTP-derived (29%), multiple-CTP-derived (26%) and MCS-derived (45%), with large heterogeneity with respect to cell morphology, proliferation rate and cell density. On average, clonal (CL) (P = 0.009) and MCS (P = 0.001) colonies exhibited higher cell density (cells per colony area) than multi-clonal (MC) colonies;however, it is interesting to note that the behavior of CL (less cells per colony and less colony area) and MCS (high cells per colony and high colony area) colonies was quite different. Overall effective proliferation rate (EPR) of the CTPs that formed CL colonies was higher than the EPR of CTPs that formed MC colonies (P = 0.02), most likely due to CTPs with varying EPR that formed the MC colonies. Finally, the authors demonstrated that lag time before first cell division of a CTP (early attribute) could potentially help predict its proliferation rate long-term. Quantitative morphological characterization using non -invasive PC-TLI serves as a reliable and reproducible technique to understand cell heteroge

关键词： Minimally invasive surgery   Retroperitoneal lymphadenectomy   Peri-operative outcomes   Testis cancer   Health services research  

摘要： Purpose To compare perioperative outcomes and perform the first cost analysis between open retroperitoneal lymph node dissection (O-RPLND) and Robotic-RPLND (R-RPLND) using a national all-payer inpatient care database. Methods Nationwide Inpatient Sample (NIS) was queried between 2013-2016 for primary RPLND and germ cell tumor. We compared cost, length of stay (LOS), and complications between O-RPLND and R-RPLND. Linear regression plots identified point of cost equivalence between R-RPLND and O-RPLND. A multivariable linear regression model was generated to analyze predictors of cost. Results 44 cases of R-RPLND and 319 cases of O-RPLND were identified. R-RPLND was associated with lower rate of complications (0% vs. 16.6%,p < 0.01) and shorter LOS [Median (IQR): 1.5 (1-3) days vs. 4 (3-6) days,p < 0.01]. Rates of ileus, genitourinary complications, and transfusions were lower with R-RPLND, but did not reach significance. On multivariable analysis, robotic approach independently contributed $4457, while each day of hospitalization contributed to an additional $2,431 to the overall model of cost. Linear regression plots determined point of cost equivalence between an R-RPLND staying a mean of 2 days was 4-5 days for O-RPLND, supporting the multivariable analysis. Total hospitalization cost was equivalent between R-RPLND and O-RPLND [Median (IQR): $15,681($12,735-$21,596) vs $16,718($11,799-$24,403),p = 0.48]-suggesting that the cost equivalency of R-RPLND is, at least in part, attributable to shorter LOS. Conclusion While O-RPLND remains the gold standard and this study is limited by selection bias of a robotic approach to RPLND, our findings suggest primary R-RPLND may represent a cost-equivalent option with decreased hospital LOS in select cases.

关键词： Primary ciliogenesis   Cilia length   Cobalt chloride   Hypoxia   Rabaptin-5   Endocytosis  

摘要： Primary cilia are microtubule-based organelles that are involved in sensing micro-environmental cues and regulating cellular homeostasis via triggering signaling cascades. Hypoxia is one of the most common environmental stresses that organ and tissue cells may often encounter during embryogenesis, cell differentiation, infection, inflammation, injury, cerebral and cardiac ischemia, or tumorigenesis. Although hypoxia has been reported to promote or inhibit primary ciliogenesis in different tissues or cultured cell lines, the role of hypoxia in ciliogenesis is controversial and still unclear. Here we investigated the primary cilia change under cobalt chloride (CoCl2)-simulated hypoxia in immortalized human retina pigment epithelial-1 (hTERT RPE-1) cells. We found CoCl2 treatment elongated primary cilia in a time- and dose-dependent manner. The prolonged cilia recovered back to near normal length when CoCl2 was washed out from the cell culture medium. Under CoCl2-simulated hypoxia, the protein expression levels of HIF-1/2 alpha and acetylated-alpha-tubulin (cilia marker) were increased, while the protein expression level of Rabaptin-5 is decreased during hypoxia. Taken together, our results suggest that hypoxia may elongate primary cilia by downregulating Rabaptin-5 involved endocytosis. The coordination between endocytosis and ciliogenesis may be utilized by cells to adapt to hypoxia. (C) 2021 Elsevier Inc. All rights reserved.