MicroRNA-424 regulates epithelial-mesenchymal transition of endometrial carcinoma by directly targeting insulin-like growth factor 1 receptor

Although numerous miRNAs are reported to contribute to the carcinogenesis of malignant tumor, the specific role of miR-424 in endometrial carcinoma is seldom reported. To explore the effect of miR-424 on epithelial-mesenchymal transition and its underlying mechanism, we detected miR-424 expression in endometrial carcinoma tissue and cells. We found that miR-424 was significantly downregulated in endometrial carcinoma tissues and cells, especially in HEC-1B cells. To perform the functional analysis, we transfected HEC-1B with miR-424-mi, miR-424-inh, mi-control, and inh-control, respectively. We found that overexpression of miR-424 significantly decreases cell proliferation and migration, accompanied with the increased E-cadherin/Vimentin expression and the transition of mesenchymal to epithelial cell phenotype. We identified that insulin-like growth factor-1 receptor (IGF-1R) was a potential target of miR-424 by computational analysis followed by luciferase reporter assays. Of note, we found that the downregulation of miR-424 in HEC-1B cells enhanced endogenous IGF-1R expression. Further mechanistic analysis revealed that forced expression of IGF-1R in miR-424-mim transfected cells remedied the weakened migration resulting from overexpression of IGF-1R. Taken together, the results of the current study demonstrated that miR-424 was a tumor suppressor for endometrial carcinoma and a favorable factor against tumor progression through targeting IGF-1R, thus providing a target for the treatment of endometrial carcinoma.     

Knockout of Nr2e3 prevents rod photoreceptor differentiation and leads to selective L-/M-cone photoreceptor degeneration in zebrafish

Mutations in the photoreceptor cell-specific nuclear receptor gene Nr2e3 increased the number of S-cone photoreceptors in human and murine retinas and led to retinal degeneration that involved photoreceptor and non-photoreceptor cells. The mechanisms underlying these complex phenotypes remain unclear. In the hope of understanding the precise role of Nr2e3 in photoreceptor cell fate determination and differentiation, we generated a line of Nr2e3 knockout zebrafish using CRISPR technology. In these Nr2e3-null animals, rod precursors undergo terminal mitoses but fail to differentiate as rods. Rod-specific genes are not expressed and the outer segment (OS) fails to form. Formation and differentiation of cone photoreceptors is normal. Specifically, there is no increase in the number of UV-cone or S-cone photoreceptors. Laminated retinal structure is maintained. After normal development, L-/M-cones selectively degenerate, with progressive shortening of OS that starts at age 1 month. The amount of cone phototransduction proteins is concomitantly reduced, whereas UV- and S-cones have normal OS lengths even at age 10 months. In vitro studies show Nr2e3 synergizes with Crx and Nrl to enhance rhodopsin gene expression. Nr2e3 does not affect cone opsin expression. Our results extend the knowledge of Nr2e3's roles and have specific implications for the interpretation of the phenotypes observed in human and murine retinas. Furthermore, our model may offer new opportunities in finding treatments for enhanced S-cone syndrome (ESCS) and other retinal degenerative diseases.     

Improving the Genome Annotation of Rhizoctonia solani Using Proteogenomics

Background Rhizoctonia solani is a pathogenic fungus that causes serious diseases in many crops, including rice, wheat, and soybeans. In crop production, it is very important to understand the pathogenicity of this fungus, which is still elusive. It might be helpful to comprehensively understand its genomic information using different genome annotation strategies.MethodsAiming to improve the genome annotation of R. solani, we performed a proteogenomic study based on the existing data. Based on our study, a total of 1060 newly identified genes, 36 revised genes, 139 single amino acid variants (SAAVs), 8 alternative splicing genes, and diverse post-translational modifications (PTMs) events were identified in R. solani AG3. Further functional annotation on these 1060 newly identified genes was performed through homology analysis with its 5 closest relative fungi.ResultsBased on this, 2 novel candidate pathogenic genes, which might be associated with pathogen-host interaction, were discovered. In addition, in order to increase the reliability and novelty of the newly identified genes in R. solani AG3, 1060 newly identified genes were compared with the newly published available R. solani genome sequences of AG1, AG2, AG4, AG5, AG6, and AG8. There are 490 homologous sequences. We combined the proteogenomic results with the genome alignment results and finally identified 570 novel genes in R. solani.ConclusionThese findings extended R. solani genome annotation and provided a wealth of resources for research on R. solani.     

Exosomes from adipose-derived mesenchymal stem cells promote survival of fat grafts by regulating macrophage polarization via let-7c

The rate of fat graft survival is a critical aspect of successful surgery and has been a matter of concern for over 20 years.Owing to their anti-inflammatory ef...     

Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/ IRF3-mediated IFN-β production

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca²⁺ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo^-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.     

乳杆菌DM9811挥发性脂肪酸组分对白色念珠菌、金黄色葡萄球菌的抑制

目的：探讨乳杆菌DM9811发酵液的挥发性脂肪酸对金黄色葡萄球菌、白色念珠菌抑制作用。方法：采用普通细菌计数法。结果：乳杆菌DM9811发酵液中挥发性脂肪酸对金黄色葡萄球菌、白色念珠菌具有抑制作用,以对白色念珠菌抑制作用最强,金黄色葡萄球菌抑制次之,两者都呈现剂量效应关系。结论：乳杆菌DM9811发酵液中挥发性脂肪酸对细菌、真菌都有明显的抑制作用。     

Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents

Upregulation and activation of phospholipases A2 (PLA2) and cyclooxygenases (COX) leading to prostaglandin E2(PGE2) production have been implicated in a number of neurodegenerative diseases. In this study, we investigated PGE2 production in primary rat astrocytes in response to agents that activate PLA2 including pro-inflammatory cytokines (IL-1beta, TNFalpha and IFNgamma), the P2 nucleotide receptor agonist ATP, and oxidants (H2O2 and menadione). Exposure of astrocytes to cytokines resulted in a time-dependent increase in PGE2 production that was marked by increased expression of secretory sPLA2 and COX-2, but not COX-1 and cytosolic cPLA2. Although astrocytes responded to ATP or phorbol ester (PMA) with increased cPLA2 phosphorylation and arachidonic acid release, ATP or PMA only caused a small increase in levels of PGE2. However, when astrocytes were first treated with cytokines, further exposure to ATP or PMA, but not H2O2 or menadione, markedly increased PGE2 production. These results suggest that ATP release during neuronal excitation or injury can enhance the inflammatory effects of cytokines on PGE2 production and may contribute to chronic inflammation seen in Alzheimer's disease.     

Isolation and molecular characterization of herpesvirus from cultured European eels Anguilla anguilla in Taiwan

A herpesvirus has been isolated for the first time from a population of European eels Anguilla anguilla cultured in a recirculated system in Taiwan. Syncytia formation was detected in EP-1 (eel epidermis) cell cultures inoculated with cell-free homogenates prepared from both integument and visceral organs of moribund fish. Inoculation of homogenates onto EK (eel kidney) cell cultures induced giant cell formation. Subsequent passages produced a consistent and progressive cytopathic effect (CPE) in cell cultures. In this study, EP-1 cell cultures infected with EEHV (European eel herpesvirus) were examined using an electron microscope. Numerous nucleocapsids of about 100 nm in diameter were found within the nucleus of infected cells, whereas enveloped particles were observed within the cytoplasm. The mature viral particle, about 235 nm in diameter, had an electron-dense core with a hexagonal nucleocapsid surrounded by a coarse capsule. Histopathological examination of moribund fish showed epithelial hyperplasia with intracytoplasmic metabolic inclusions in the skin. Macrophage aggregates were found in liver, spleen, and kidney. A pair of primers designed from channel catfish virus and salmonid herpesvirus 1 was used in a polymerase chain reaction. A 402 bp fragment was amplified and cloned from genomic DNA of EEHV. The nucleotide homology was 99% (298 of 300) with DNA polymerase of eel herpesvirus (anguillid herpesvirus). EEHV nucleic acids were detected within melanomacrophages in the skin, liver, spleen and kidney by in situ hybridization (ISH).     

Inheritance and expression of the cry1Ab gene in Bt ( Bacillus thuringiensis) transgenic rice

The inheritance and expression patterns of the cry1Ab gene were studied in the progenies derived from different Bt (Bacillus thuringiensis) transgenic japonica rice lines under field conditions. Both Mendelian and distorted segregation ratios were observed in some selfed and crossed F₂ populations. Crosses between japonica intra-subspecies had no significant effect on the segregation ratios of the cry1Ab gene, but crossing between japonica and indica inter-subspecies led to distorted segregation of the cry1Ab gene in the F₂ population. Field-release experiments indicated that the cry1Ab gene was stably transmitted in an intact manner via successive sexual generations, and the concentration of the Cry1Ab protein was kept quantitatively stable up to the R₆ generation. The cry1Ab gene, driven by the maize ubiquitin promoter, displayed certain kinds of spatial and temporal expression patterns under field conditions. The content of the Cry1Ab protein varied in different tissues of the main stems, the primary tillers and the secondary tillers. Higher levels of the Cry1Ab protein were found in the stems, leaves and leaf sheaths than in the roots, while the lowest level was detected in grains at the maturation stage. The content of the Cry1Ab protein in the leaves peaked at the booting stage and was lowest at the heading stage. Furthermore, the Cry1Ab content of cry1Ab expression in different tissues of transgenic rice varied individually with temperature. Received: 17 April 2001 / Accepted: 7 May 2001