Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73-AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP-73-AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73-AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73-AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73-AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73-AS1 suppressed the expression of the known oncogenic miR-200a. Taken together, these data highlight the prognostic potential of TP73-AS1 for PC patients and highlight it as a potential anti-PDAC therapeutic target. 相似文献
Plasmonics - Large-scale ordered two-dimensional (2D) superlattices at oil/water interface were fabricated using single-crystal Au nanospheres (NSs) with different diameters as building blocks. A... 相似文献
Elevated intraocular pressure (IOP) is a risk factor in glaucoma, a group of irreversible blinding diseases. Endogenous lipids may be involved in regulation of IOP homeostasis. We present comparative fold analysis of phospholipids and sphingolipids of aqueous humour and trabecular meshwork from human control vs primary open-angle glaucoma and mouse control (normotensive) vs ocular hypertensive state. The fold analysis in control vs disease state was based on ratiometric mass spectrometric data for above classes of lipids. We standardized in vitro assays for rapid characterization of lipids undergoing significant diminishment in disease state. Evaluation of lipids using in vitro assays helped select a finite number of lipids that may potentially expand cellular interstitial space embedded in an artificial matrix or increase fluid flow across a layer of cells. These assays reduced a number of lipids for initial evaluation using a mouse model, DBA/2J with spontaneous IOP elevation. These lipids were then used in other mouse models for confirmation of IOP lowering potential of a few lipids that were found promising in previous assessments. Our results provide selected lipid molecules that can be pursued for further evaluation and studies that may provide insight into their function. 相似文献
Chikungunya virus (CHIKV) is a mosquito‐transmitted alphavirus, and its infection can cause long‐term debilitating arthritis in humans. Currently, there are no licensed vaccines or therapeutics for human use to combat CHIKV infections. In this study, we explored the feasibility of using an anti‐CHIKV monoclonal antibody (mAb) produced in wild‐type (WT) and glycoengineered (?XFT) Nicotiana benthamiana plants in treating CHIKV infection in a mouse model. CHIKV mAb was efficiently expressed and assembled in plant leaves and enriched to homogeneity by a simple purification scheme. While mAb produced in ?XFT carried a single N‐glycan species at the Fc domain, namely GnGn structures, WT produced mAb exhibited a mixture of N‐glycans including the typical plant GnGnXF3 glycans, accompanied by incompletely processed and oligomannosidic structures. Both WT and ?XFT plant‐produced mAbs demonstrated potent in vitro neutralization activity against CHIKV. Notably, both mAb glycoforms showed in vivo efficacy in a mouse model, with a slight increased efficacy by the ?XFT‐produced mAbs. This is the first report of the efficacy of plant‐produced mAbs against CHIKV, which demonstrates the ability of using plants as an effective platform for production of functionally active CHIKV mAbs and implies optimization of in vivo activity by controlling Fc glycosylation. 相似文献
Exosomes are membrane‐bound extracellular vesicles that are produced in the endosomal compartment of most mammalian cell types and then released. Exosomes are effective carriers for the intercellular material transfer of material that can influence a series of physiological and pathological processes in recipient cells. Among loaded cargoes, non‐coding RNAs (ncRNAs) vary for the exosome‐producing cell and its homeostatic state, and characterization of the biogenesis and secretion of exosomal ncRNAs and the functions of these ncRNAs in skeletal muscle myogenesis remain preliminary. In this review, we will describe what is currently known of exosome biogenesis, release and uptake of exosomal ncRNAs, as well as the varied functions of exosomal miRNAs in skeletal muscle myogenesis. 相似文献
We aimed to illustrate the roles and molecular mechanisms of ID2-AS1 in parkinson’s disease (PD). Methods: qRT-PCR detected the expression of ID2-AS1. CCK-8, LDH release assays the effect of ID2-AS1 knockdown on PD cells. Flow cytometry and Western Blot were used to detect the effect of ID2-AS1 inhibition on PD cell apoptosis. ELISA analysis showed that ID2-AS1 inhibition can reduce the inflammation of PD cells. ROS activity assay showed that inhibiting ID2-AS1 attenuated the oxidative stress induced by 1-methy1-4-phenylpyridinium (MPP+). RNA binding protein immunoprecipitation assay showed that ID2-AS1 is mainly located in the cytoplasm. The luciferase reporter assay is used to verify the interaction. In our study, ID2-AS1 was concentration-dependently and time-dependently up-regulated in MPP+?-treated human neuroblastoma cell line SH-SY5Y. ID2-AS1 knockdown enhanced cell proliferation and decreased cell death in PD cells. Knockdown of ID2-AS1 attenuates MPP+?-induced cytotoxicity in SH-SY5Y cells. ID2-AS1 is a sponge of miR-199a-5p. IFNAR1 is a target of miR-199a-5p. Inhibition of miR-199a-5p and overexpression of IFNAR1 alleviate the inhibitory effect of ID2-AS1 knockdown on MPP+?triggered neuronal injury. Inhibition of miR-199a-5p and overexpression of IFNAR1 alleviate the inhibitory effect of ID2-AS1 knockdown on MPP+?-triggered JAK2/STAT1 activation. Overall, down-regulation of ID2-AS1 alleviated the neuronal injury in PD through regulating miR-199a-5p/IFNAR1/JAK2/STAT1 axis.