يعرض 1 - 10 نتائج من 17 نتيجة بحث عن '"Xiaofang Xu"', وقت الاستعلام: 1.17s تنقيح النتائج
  1. 1

    المصدر: Cell Death and Disease, Vol 12, Iss 12, Pp 1-14 (2021)
    Cell Death & Disease

    الوصف: Retinoblastoma is a childhood retinal tumour that is the most common primary malignant intraocular tumour. However, it has been challenging to identify the cell types associated with genetic complexity. Here, we performed single-cell RNA sequencing on 14,739 cells from two retinoblastoma samples to delineate the heterogeneity and the underlying mechanism of retinoblastoma progression. Using a multiresolution network-based analysis, we identified two major cell types in human retinoblastoma. Cell trajectory analysis yielded a total of 5 cell states organized into two main branches, and the cell cycle-associated cone precursors were the cells of origin of retinoblastoma that were required for initiating the differentiation and malignancy process of retinoblastoma. Tumour cells differentiation reprogramming trajectory analysis revealed that cell-type components of multiple tumour-related pathways and predominantly expressed UBE2C were associated with an activation state in the malignant progression of the tumour, providing a potential novel “switch gene” marker during early critical stages in human retinoblastoma development. Thus, our findings improve our current understanding of the mechanism of retinoblastoma progression and are potentially valuable in providing novel prognostic markers for retinoblastoma.

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    المصدر: Carcinogenesis. 42:1056-1067

    الوصف: This study tried to explore the molecular mechanism underlying progression of lung adenocarcinoma (LUAD) and discuss the extracellular communication between cancer cells and vascular endothelial cells. Roughly, differential analysis was carried out to note that miR-30a-5p was lowly expressed in LUAD, whereas CCNE2 was highly expressed. Cell functional experiments demonstrated that overexpressed miR-30a-5p led to suppressed cell abilities in proliferation, migration and invasion. Dual-luciferase reporter gene assay and RNA immunoprecipitation verified the binding of miR-30a-5p and CCNE2, as well as decreased mRNA and protein expression of CCNE2 with miR-30a-5p overexpression. Simultaneous up-regulation of miR-30a-5p and CCNE2 reversed the promotion of CCNE2 on malignant behaviors of LUAD cells. In vivo mice experiments exhibited that high miR-30a-5p expression hindered tumor growth. Additionally, miR-30a-5p was localized on the Extracellular Vesicles microRNA (EVmiRNA) database. MiR-30a-5p was abundant in exosomes derived from vascular endothelial cells. To validate that miR-30a-5p could be delivered to LUAD cells via exosomes and then make an effect, exosomes from vascular endothelial cells were first extracted and identified by transmission electron microscopy and detection of exosomal marker proteins (Alix, CD63, TSG101). Sequentially, the extracted exosomes were labeled with DIO to note that exosomes could be internalized by cancer cells. Further experiments indicated that miR-30a-5p was increased in cancer cells co-cultured with exosomes, which in turn suppressed cell malignant behaviors and made cell cycle arrest. In all, our findings clarified that exosomes derived from vascular endothelial cells delivered miR-30a-5p to LUAD cells to affect tumor malignant progression via the miR-30a-5p/CCNE2 axis.

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    المصدر: Neuroscience. 418:25-36

    الوصف: Histone deacetylase inhibitors (HDACis) have displayed neuroprotective effects in animal models of retinal ischemia/reperfusion (I/R) injury. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription factor responds to oxidative damage. We investigated the role of Nrf2 in retinal I/R injury, and further explored the mechanisms underlying Nrf2-mediated neuroprotection exerted by HDACi. High intraocular pressure was used to establish retinal I/R model in wild type (WT) and Nrf2 knockout (KO) mice. Nrf2 KO mice displayed more severe retinal damage after I/R. Trichostatin A (TSA) was administered to both WT and Nrf2 KO mice with retinal I/R damage. TSA significantly diminished the retinal ganglion cell degeneration in WT mice but offered no notable protection in Nrf2 KO mice. TSA markedly promoted Nrf2 nuclear translocation and its acetylation. In addition, TSA upregulated Nrf2 downstream proteins, such as Ho-1 and Nqo1, in retinal tissues. In the retinal neuronal cell line 661W, TSA reduced the expression of proinflammatory cytokines, Il-1β, Il-6, Tnf-α and Mmp-9, and it upregulated Bdnf under oxidative stress. However, this trend was not continued after silencing Nrf2. Chromatin immunoprecipitation assay demonstrated that Nrf2 at the Ho-1 promoter significantly increased transcriptional activity after oxidative stress induction. Nrf2, which is dispensable in HDACi-mediated neuroprotection, plays a major neuroprotective role in retinal I/R injury.

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    المصدر: American journal of physiology. Lung cellular and molecular physiology. 321(3)

    الوصف: The paramyxoviridae, respiratory syncytial virus (RSV), and murine respirovirus are enveloped, negative-sense RNA viruses that are the etiological agents of vertebrate lower respiratory tract infections (LRTIs). We observed that RSV infection in human small airway epithelial cells induced accumulation of glycosylated proteins within the endoplasmic reticulum (ER), increased glutamine-fructose-6-phosphate transaminases (GFPT1/2) and accumulation of uridine diphosphate (UDP)- N-acetylglucosamine, indicating activation of the hexosamine biosynthetic pathway (HBP). RSV infection induces rapid formation of spliced X-box binding protein 1 (XBP1s) and processing of activating transcription factor 6 (ATF6). Using pathway selective inhibitors and shRNA silencing, we find that the inositol-requiring enzyme (IRE1α)-XBP1 arm of the unfolded protein response (UPR) is required not only for activation of the HBP, but also for expression of mesenchymal transition (EMT) through the Snail family transcriptional repressor 1 (SNAI1), extracellular matrix (ECM)-remodeling proteins fibronectin (FN1), and matrix metalloproteinase 9 (MMP9). Probing RSV-induced open chromatin domains by ChIP, we find XBP1 binds and recruits RNA polymerase II to the IL6, SNAI1, and MMP9 promoters and the intragenic superenhancer of glutamine-fructose-6-phosphate transaminase 2 (GFPT2). The UPR is sustained through RSV by an autoregulatory loop where XBP1 enhances Pol II binding to its own promoter. Similarly, we investigated the effects of murine respirovirus infection on its natural host (mouse). Murine respirovirus induces mucosal growth factor response, EMT, and the indicators of ECM remodeling in an IRE1α-dependent manner, which persists after viral clearance. These data suggest that IRE1α-XBP1s arm of the UPR pathway is responsible for paramyxovirus-induced metabolic adaptation and mucosal remodeling via EMT and ECM secretion.

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    المصدر: J Thorac Dis

    الوصف: Background Currently, modified inflation-deflation is considered the easiest way to identify the intersegmental plane during pulmonary segmentectomy. However, this approach requires a wait of about 10-20 min during the operative procedure. Therefore, we optimized the procedure, which we call no-waiting segmentectomy. In this study, we compared no-waiting segmentectomy with the modified inflation-deflation method. Methods We studied 123 consecutive patients with pulmonary ground-glass nodules who underwent segmentectomy by uniportal video-assisted thoracoscopic surgery in a single medical group from January 2019 to April 2020. Forty-five patients underwent the modified inflation-deflation method and 78 patients underwent the no-waiting method. The no-waiting procedure involved severing of the target segmental pulmonary artery, inflating the lung with atmospheric air, dissecting the hilum, and dividing the target segmental bronchus. The entire procedure could be performed at a stretch and no pause was needed. We compared the two methods for surgery time, bleeding volume, drainage time, and postoperative hospital stay. Propensity-score matching was used to adjust the baseline characteristics. Results Thirty-three pairs of 123 patients were successfully matched. Before propensity-score matching, there was no difference between the two methods in terms of surgery time, bleeding volume, drainage time, and postoperative hospital stay. After propensity-score matching, the surgery time in the no-waiting group was significantly shorter than that in the modified inflation-deflation method group (80.12±35.53 vs. 102.97±48.07 min, P=0.03). There was no difference between the two methods in terms of bleeding volume, drainage time, and postoperative hospital stay. Conclusions No-waiting segmentectomy was associated with a reduced surgery time, compared to that associated with modified inflation-deflation segmentectomy. Furthermore, no-waiting segmentectomy did not increase bleeding volume, drainage time, and postoperative hospital stay. Thus, no-waiting segmentectomy is an optional optimized approach for segmentectomy.

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    المصدر: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research

    الوصف: Background The aim of this study was to compare the efficacy of air and perfluoropropane (C3F8) combined with vitrectomy to treat myopic foveoschisis (MF). Material/Methods A retrospective comparison of a consecutive series of surgical patients was performed. Ninety-seven eyes of 91 patients with MF were assigned to undergo 23G vitrectomy. After internal limiting membrane (ILM) peeling, the vitreous cavity was filled with air in 48 eyes of 45 patients (Air Group). Fluid-air exchange was performed in 49 eyes of 46 patients (C3F8 Group) followed by an injection of 14% C3F8. Patients were evaluated using best-corrected visual acuity (BCVA) and optical coherence tomography. Results Preoperatively, there was no significant difference in clinical features between the groups. After surgery, BCVA was markedly improved and the foveoschisis height was reduced in both groups compared with baseline (P0.05). No significant differences were noted in BCVA improvement and retinal restoration (P=0.33 and 0.39, respectively) in the mild and moderate subgroups (foveoschisis height ≤400 μm) between the tamponades. However, in the severe group (foveoschisis height >400 μm), C3F8 had a more favorable cure rate and foveoschisis height reduction improvement compared with air (P=0.04 and 0.04, respectively) at the last visit. Conclusions Vitrectomy combined with ILM peeling is effective in the treatment of myopic foveoschisis, and the choice of tamponade depends on the severity of foveoschisis. Air can be used for patients with a foveoschisis height ≤400 μm, but C3F8 is more effective for patients with a foveoschisis height >400 μm.

  7. 7

    المصدر: Journal of Diabetes Research, Vol 2018 (2018)
    Journal of Diabetes Research

    الوصف: Objective. To examine the changes in retinal thickness of patients with diabetes without DR. Designs. A randomization, crossover, retrospective practice. Participants. 43 diabetic patients and 43 ethnic-, age-, and sex-matched controls. Methods. Full retinal thicknesses of ten areas were assessed using spectral domain optical coherence tomography. Confounding variables, such as age, gender, and glycated haemoglobin (HbA1c) level, were assessed by regression analysis. Main Outcome Measures. Mean retinal thickness of ten areas. Results. The mean thickness of the fovea was 215.8 ± 18.9 μm in the diabetes group and 222.0 ± 18.6 μm in the control group (p=0.04). The mean thickness of the temporal parafovea was 319.9 ± 16.7 μm in the diabetes group and 326.0 ± 14.4 μm in the control group (p=0.01). The mean thickness of the temporal perifovea was 276.4 ± 27.9 μm in the diabetes group and 284.8 ± 17.4 μm in the control group (p=0.02). There were no significant differences in retinal thickness between groups in other areas (p>0.05). Regression analysis revealed that decreased retinal thickness of the temporal perifovea was associated with a higher HbA1c level (>8.7%) (p=0.04). Conclusion and Relevance. Subtle structural changes in the retina may occur in diabetes without DR. Decreased retinal thickness appeared to begin in the fovea and temporal areas. A high HbA1c level was the main factor influencing retinal thickness.

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    المصدر: Melanoma Research. 25:119-126

    الوصف: Uveal melanoma (UM) is an intraocular malignant tumor in adults that is characterized by rapid progression and recurrence. Irradiation has become the primary therapy for UM patients who are not candidates for surgery. However, after large-dose fraction irradiation treatment, some patients undergo subsequent enucleation because of radiotherapy-related complications. This situation has raised concerns on how to optimize the effectiveness of radiation treatment. Recent investigations of microRNAs are changing our understanding of UM tumor biology and are helping to identify novel targets for radiotherapy. The radioresistant UM cell lines OM431 and OCM1 were selected and exposed to irradiation, and let-7b was found to be downregulated after exposure. We then confirmed that let-7b mimics could inhibit UM growth both in vitro and in vivo. More specifically, transfection with let-7b mimics markedly resensitized OCM1 and OM431 cells to irradiation by reducing the population of S-phase cells. Cyclin D1 plays a vital role in cell cycle arrest, which is induced by let-7b overexpression. Cyclin D1 is also a target of let-7b and its expression is suppressed by upregulation of let-7b. Collectively, our results indicate that let-7b overexpression can in turn downregulate cyclin D1 expression and enhance the radiosensitivity of UM through cell cycle arrest. Let-7b could serve as a marker for radiosensitivity and could enhance the therapeutic benefit of UM cell irradiation.

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    المصدر: Experimental and Therapeutic Medicine

    الوصف: The aim of the present study was to evaluate the clinical results of pars plana vitrectomy (PPV) combined with the surgical enlargement of internal limiting membrane (ILM) peeling in patients who had previously undergone failed idiopathic macular hole (IMH) surgery. In the study, 134 eyes from 130 IMH patients who had received PPV combined with ILM peeling surgery (2 disk diameters) were analyzed. Within this cohort, 14 eyes had IMHs that were not closed, of which 13 eyes underwent a second surgery involving enlargement of the ILM peeling. The extent of the ILM peeling was increased to the vascular arcades of the posterior fundus in the secondary surgery. Of the 13 eyes that underwent secondary surgery, five were in stage III and nine were in stage IV. The second surgery successfully achieved IMH closure in 61.5% (8/13) of the eyes. The IMH was completely closed following surgery and the logMAR vision increased from 0.98 to 0.84 (P=0.013) in the 8 successfully treated cases. The surgical enlargement of ILM peeling closed the IMHs and improved vision in the majority of patients. In addition, the procedures were safe. Therefore, the results of the present study indicate that enlargement of ILM peeling may be an effective therapy for patients who have previously undergone the failed surgical correction of an IMH.

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    المصدر: Experimental and Therapeutic Medicine

    الوصف: IDH2 encodes a mitochondrial metabolic enzyme that converts isocitrate to α-ketoglutarate (α-KG) by reducing nicotinamide adenine dinucleotide phosphate (NADP(+)) to NADPH and participates in the citric acid cycle for energy production. Notably, this gene has been shown to be critical for cell proliferation. The abnormal expression of IDH2 has been reported in several types of cancer, and mutations in IDH2 have been identified in gliomas and acute myelogenous leukemia. The overexpression of IDH2 has been reported in endometrial, prostate and testicular cancer as well as in Kashin-Beck disease. In this study, we observed that IDH2 expression was significantly downregulated in early phase but was upregulated in advanced phase colon carcinoma compared to peritumoral tissues. In addition, we demonstrated that the growth of a colon carcinoma cell line was inhibited by IDH2-siRNA and increased following transfection with an IDH2-overexpressing plasmid. These results indicate that IDH2 may play a unique role in the development of colon carcinoma.