61 research outputs found

    Long non-coding RNA ATB promotes malignancy of esophageal squamous cell carcinoma by regulating miR-200b/Kindlin-2 axis

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    Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related death, especially in China. In addition, the prognosis of late stage patients is extremely poor. However, the biological significance of the long non-coding RNA lnc-ATB and its potential role in ESCC remain to be documented. In this study, we investigated the role of lnc-ATB and the underlying mechanism promoting its oncogenic activity in ESCC. Expression of lnc-ATB was higher in ESCC tissues and cell lines than that in normal counterparts. Upregulated lnc-ATB served as an independent prognosis predictor of ESCC patients. Moreover, loss-of-function assays in ESCC cells showed that knockdown of lnc-ATB inhibited cell proliferation and migration both in vitroand in vivo. Mechanistic investigation indicated that lnc-ATB exerted oncogenic activities via regulating Kindlin-2, as the anti-migration role of lnc-ATB silence was attenuated by ectopic expression of Kindlin-2. Further analysis showed that lnc-ATB functions as a molecular sponge for miR-200b and Kindlin-2. Dysregulated miR-200b/Kindlin-2 signaling mediated the oncogenic activity of lnc-ATB in ESCC. Our results suggest that lnc-ATB predicts poor prognosis and may serve as a potential therapeutic target for ESCC patients

    Organelle-specific anchored delivery system stretching a reversal of tumor hypoxia microenvironment to a combinational chemo-photothermal therapy

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    Direct delivery to an organelle-specific point can boost the efficacy of therapy procedures to new heights. Among other subcellular organelles, mitochondria generate ATP as intracellular powerhouse, and are associated with multiple aspects of tumorigenesis and tumor development. Here, a mitochondrial anchored biomimetic nanoplatform (CZACN) is designed and its reversal of tumor hypoxia microenvironment underlying the mitochondria-located chemo-photothermal therapy is studied. After shuttling into cancer cells, therapeutic payloads including cisplatin (CDDP) and Au nanozymes are controllably released in the ATP-overexpressed mitochondria. CDDP generates O2â ¢â , forms H2O2 for a chemical fuel in the next reaction, and damages mitochondrial DNA. Meanwhile, the catalase-like Au nanozymes catalyze the produced hydrogen peroxide for oxygen supply to relieve hypoxic tumor microenvironment, offering cytotoxic singlet oxygen against cancer cells under NIR treatment. As a result of cancer-cell self-recognition, mitochondria-targeted therapy, and photothermal conversion ability, the fabricated CZACNs obtained 89.2 ± 3.70% of tumor growth inhibition under NIR irradiation and constrained the dose-limiting toxicity of CDDP, as well. These findings reinforce the synergistic effect of organelle-specific navigation and in situ oxygen self-sufficiency for combinational chemo-photothermal therapy.X.C., X.Y., and L.Z. contributed equally to this work. This work has been supported by the National Natural Science Foundation of China (22003038, 81922037, and 11575107), the Shanghai University-Universal Medical Imaging Diagnostic Research Foundation (19H00100), Shanghai Biomedical Science and Technology Support Project (19441903600), the Program for Changjiang Scholars and Innovative Research Team in University (IRT13078). The authors would like to thank the workers from Shiyanjia Lab (www.shiyanjia.com) for the ICP-OES analysis

    Two-phase behavior in strained thin films of hole-doped manganites

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    We present a study of the effect of biaxial strain on the electrical and magnetic properties of thin films of manganites. We observe that manganite films grown under biaxial compressive strain exhibit island growth morphology which leads to a non-uniform distribution of the strain. Transport and magnetic properties of these films suggest the coexistence of two different phases, a metallic ferromagnet and an insulating antiferromagnet. We suggest that the high strain regions are insulating while the low strain regions are metallic. In such non-uniformly strained samples, we observe a large magnetoresistance and a field-induced insulator to metal transition.Comment: 5 pages ReVTeX, 5 figures included, Figures 3, 4 and 5 low resolution, high resolution figures available on request from authors, submitted to Phys. Rev.

    Equilibrium shapes and energies of coherent strained InP islands

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    The equilibrium shapes and energies of coherent strained InP islands grown on GaP have been investigated with a hybrid approach that has been previously applied to InAs islands on GaAs. This combines calculations of the surface energies by density functional theory and the bulk deformation energies by continuum elasticity theory. The calculated equilibrium shapes for different chemical environments exhibit the {101}, {111}, {\=1\=1\=1} facets and a (001) top surface. They compare quite well with recent atomic-force microscopy data. Thus in the InP/GaInP-system a considerable equilibration of the individual islands with respect to their shapes can be achieved. We discuss the implications of our results for the Ostwald ripening of the coherent InP islands. In addition we compare strain fields in uncapped and capped islands.Comment: 10 pages including 6 figures. Submitted to Phys. Rev. B. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

    Population genomics of an icefish reveals mechanisms of glacier-driven adaptive radiation in Antarctic notothenioids

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    Background Antarctica harbors the bulk of the species diversity of the dominant teleost fish suborder—Notothenioidei. However, the forces that shape their evolution are still under debate. Results We sequenced the genome of an icefish, Chionodraco hamatus, and used population genomics and demographic modelling of sequenced genomes of 52 C. hamatus individuals collected mainly from two East Antarctic regions to investigate the factors driving speciation. Results revealed four icefish populations with clear reproduction separation were established 15 to 50 kya (kilo years ago) during the last glacial maxima (LGM). Selection sweeps in genes involving immune responses, cardiovascular development, and photoperception occurred differentially among the populations and were correlated with population-specific microbial communities and acquisition of distinct morphological features in the icefish taxa. Population and species-specific antifreeze glycoprotein gene expansion and glacial cycle-paced duplication/degeneration of the zona pellucida protein gene families indicated fluctuating thermal environments and periodic influence of glacial cycles on notothenioid divergence. Conclusions We revealed a series of genomic evidence indicating differential adaptation of C. hamatus populations and notothenioid species divergence in the extreme and unique marine environment. We conclude that geographic separation and adaptation to heterogeneous pathogen, oxygen, and light conditions of local habitats, periodically shaped by the glacial cycles, were the key drivers propelling species diversity in Antarctica.info:eu-repo/semantics/publishedVersio

    Biodiversity and adaptive evolution of Antarctic notothenioid fishes

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    Hematogenesis Adaptation to Long-Term Hypoxia Acclimation in Zebrafish (<i>Danio rerio</i>)

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    When fish live in the wild or are cultured artificially, they will inevitably suffer from hypoxia. At the same time, blood physiological indexes represent the physiological state of fish. In order to study the effect of long-term hypoxia acclimation on fish hematogenesis, we cultured zebrafish embryos into adulthood in a hypoxia incubator (1.5 ± 0.2 mg/L). Then we compared the hematological parameters of zebrafish cultured in normoxia and hypoxia conditions. Transcriptome sequencing analysis of the main hematopoietic tissue, the head kidney, was also compared between the two groups. Results showed that the number of erythrocytes increased significantly in the long-term hypoxia acclimated group, while the size of several cell types, such as red blood cells, eosinophils, basophils, small lymphocytes and thrombocytes, decreased significantly. The transcriptomic comparisons revealed that there were 6475 differentially expressed genes (DEGs) between the two groups. A Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that hematopoiesis and cell proliferation signaling were the most significantly enriched pathways in the head kidney of hypoxia acclimated zebrafish. In addition, many genes involved in the hematopoietic process showed significantly higher levels of expression in the hypoxia acclimated zebrafish, when compared to the normoxia zebrafish. When considered together, these data allowed us to conclude that long-term hypoxia can promote the hematopoiesis process and cell proliferation signaling in the zebrafish head kidney, which resulted in higher red blood cell production. Higher numbers of red blood cells allow for better adaptation to the hypoxic environment. In conclusion, this study provides a basis for the in-depth understanding of the effects of hypoxia on hematogenesis in fish species
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