91 research outputs found

    Scoulerine promotes cytotoxicity and attenuates stemness in ovarian cancer by targeting PI3K/AKT/mTOR axis

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    In women, ovarian cancer is a common gynecological cancer associated with poor prognosis, reoccurrence and chemoresistance. Scoulerine, a benzylisoquinoline alkaloid, has been reported effective against several carcinomas. Thus, we investigated the impact of scoulerine on ovarian cancer cells (OVCAR3). Cell viability was assessed by MTT assay, migration was determined by Boyden Chamber assay, while the invasion was monitored by Boyden Chamber assay using the matrigel. The stemness properties of OVCAR3 cells were observed by tumorsphere assay. Epithelial to mesenchymal transition (EMT) and stemness-related protein markers were monitored by real-time PCR analysis and immunoblotting. Scoulerine inhibits the viability of OVCAR3 cells with the IC50 observed at 10 µmol L–1 after 48 h treatment. Scoulerine inhibited the colony-forming ability, migration and invasiveness of OVCAR3 cells in a dose-dependent fashion. Scoulerine treatment also drastically reduced the spheroid-forming ability of OVCAR3 cells. The mesenchymal and stemness-related markers like N-cadherin, vimentin, CD-44, Oct-4, Sox-2 and Aldh1A1 were downregulated, whereas the epithelial markers like E-cadherin and CD-24 were upregulated in scoulerine-treated cells. The upstream PI3K/Akt/mTOR-axis was downregulated in scoulerine-treated cells. We concluded that scoulerine successfully perturbs the cancerous properties of OVCAR3 cells by targeting the PI3K/Akt/mTOR axis. In vivo studies revealed a substantial decrease in tumor mass and volume after scoulerine treatment. Furthermore, scoulerine treatment was found to decrease oxidative stress factors in ovarian cancer mice model. Scoulerine is a potential anticancer agent against ovarian cancer and can be considered as a lead molecule for this malignancy, provided further investigations are performed

    Anoikis resistance regulates immune infiltration and drug sensitivity in clear-cell renal cell carcinoma: insights from multi omics, single cell analysis and in vitro experiment

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    BackgroundAnoikis is a form of programmed cell death essential for preventing cancer metastasis. In some solid cancer, anoikis resistance can facilitate tumor progression. However, this phenomenon is underexplored in clear-cell renal cell carcinoma (ccRCC).MethodsUsing SVM machine learning, we identified core anoikis-related genes (ARGs) from ccRCC patient transcriptomic data. A LASSO Cox regression model stratified patients into risk groups, informing a prognostic model. GSVA and ssGSEA assessed immune infiltration, and single-cell analysis examined ARG expression across immune cells. Quantitative PCR and immunohistochemistry validated ARG expression differences between immune therapy responders and non-responders in ccRCC.ResultsARGs such as CCND1, CDKN3, PLK1, and BID were key in predicting ccRCC outcomes, linking higher risk with increased Treg infiltration and reduced M1 macrophage presence, indicating an immunosuppressive environment facilitated by anoikis resistance. Single-cell insights showed ARG enrichment in Tregs and dendritic cells, affecting immune checkpoints. Immunohistochemical analysis reveals that ARGs protein expression is markedly elevated in ccRCC tissues responsive to immunotherapy.ConclusionThis study establishes a novel anoikis resistance gene signature that predicts survival and immunotherapy response in ccRCC, suggesting that manipulating the immune environment through these ARGs could improve therapeutic strategies and prognostication in ccRCC

    Along-strike segmentation of the South China Sea margin imposed by inherited pre-rift basement structures

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    Multibeam bathymetric, seismic and borehole data are used to investigate a large-scale strike-slip structure, the Baiyun-Liwan Fault Zone, in the northern South China Sea. This fault zone comprises NW- to NE-striking faults and negative flower structures that were generated by oblique extensional displacement. Notably, the interpreted data reveals that the Baiyun-Liwan Fault Zone was active during the Cenozoic, recording intense magmatism, and accommodating significant intraplate deformation during progressive continental rifting and ocean spreading. It bounds two distinct crustal segments and played a significant role in segmenting the northern margin of the South China Sea. The geometry of faults and strata within the Baiyun-Liwan Fault Zone also controlled local sediment routing and depocentre evolution during the Cenozoic. As basement and syn-rift structures change markedly across the Baiyun-Liwan Fault Zone, we propose this structure to be inherited from a lithospheric-scale fault zone separating the Mesozoic arc from forearc-related terrains. We therefore stress the importance of pre-existing structures in the development of rifted margins, with the example provided by the Baiyun-Liwan Fault Zone having profound implications for palaeogeographic reconstructions in the South China Sea. At present, the Baiyun-Liwan Fault Zone is incised by the Pearl River Canyon and eroded by recurrent submarine landslides, forming a major area of sediment bypass towards the abyssal plain

    Mapping current trends and hotspots in myasthenia gravis from 2003 to 2022: a bibliometric analysis

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    IntroductionResearch on myasthenia gravis (MG) has undergone rapid development in recent years. This article aimed to elucidate the characteristics of MG publications over the past 20 years and analyze emerging trends using bibliometric methods.MethodsInformation on MG articles was obtained from the Web of Science Core Collection and stored in Excel for quantitative analyses. Bibliometric analyses were performed using CiteSpace and VOSviewer to visualize publications according to countries/regions, institutions, journals, and authors.ResultsA total of 3,610 publications were included in the analysis. The USA had the highest number of publications (NP) and H-index. Among the institutions, the University of Oxford had the highest NP, followed by the University of Toronto and Duke University. Close cooperation was observed among countries and institutions. The most productive author was Renato Mantegazza, followed by Jan J. Verschuuren, and Amelia Evoli. Muscle & Nerve published the most articles on MG, followed by the Journal of Neuroimmunology and Neuromuscular Disorders. The keyword with the highest strength is “neuromuscular transmission,” followed by “safety” and “rituximab.” Co-citation analysis includes 103 publications cited at least 65 times, categorized into four clusters. Additionally, 123 keywords cited more than 40 times were analyzed and divided into five clusters.ConclusionThis bibliometric analysis shows the framework of research over the past 20 years by mapping the scholarly contributions of various countries or regions, institutions, journals, and authors in MG. The analysis also explores future trends and prospective directions, emphasizing individualized treatment based on subtypes, novel immunotherapeutic approaches, and thymectomy

    Inhibition of MicroRNA-96 Ameliorates Cognitive Impairment and Inactivation Autophagy Following Chronic Cerebral Hypoperfusion in the Rat

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    Background/Aims: Chronic cerebral hypoperfusion (CCH) is a high-risk factor for vascular dementia and Alzheimer’s disease. Autophagy plays a critical role in the initiation and progression of CCH. However, the underlying mechanisms remain unclear. In this study, we identified the effect of a microRNA (miR) on autophagy under CCH. Methods: A CCH rat model was established by two-vessel occlusion (2VO). Learning and memory abilities were assessed by the Morris water maze. The protein levels of LC3, beclin-1, and mTOR were detected by western blotting and immunofluorescence assays, miR-96 expression was assessed by real-time PCR, luciferase assays were used to determine the effect of miR-96 on the 3′ untranslated region (UTR) of mTOR, and the number of autophagosomes was examined by electron microscopy. Results: The level of miR-96 was significantly increased in 2VO rats, and inhibition of miR-96 ameliorated the cognitive impairment induced by 2VO. Furthermore, the number of LC3- and beclin-1-positive autophagosomes was increased in 2VO rats, and was decreased after miR-96 antagomir injection. However, the protein level of mTOR was reduced in 2VO rats, and it was down-regulated by miR-96 overexpression and up-regulated by miR-96 inhibition in 2VO rats and primary culture cells. Moreover, the luciferase activity of the 3′-UTR of mTOR was suppressed by miR-96, which was relieved by mutation of the miR-96 binding sites. Conclusion: Our study demonstrated that miR-96 may play a key role in autophagy under CCH by regulating mTOR; therefore, miR-96 may represent a potential therapeutic target for CCH

    The Genomic Footprints of the Fall and Recovery of the Crested Ibis

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    Human-induced environmental change and habitat fragmentation pose major threats to biodiversity and require active conservation efforts to mitigate their consequences. Genetic rescue through translocation and the introduction of variation into imperiled populations has been argued as a powerful means to preserve, or even increase, the genetic diversity and evolutionary potential of endangered species [1-4]. However, factors such as outbreeding depression [5, 6] and a reduction in available genetic diversity render the success of such approaches uncertain. An improved evaluation of the consequence of genetic restoration requires knowledge of temporal changes to genetic diversity before and after the advent of management programs. To provide such information, a growing number of studies have included small numbers of genomic loci extracted from historic and even ancient specimens [7, 8]. We extend this approach to its natural conclusion, by characterizing the complete genomic sequences of modern and historic population samples of the crested ibis (Nipponia nippon), an endangered bird that is perhaps the most successful example of how conservation effort has brought a species back from the brink of extinction. Though its once tiny population has today recovered to >2,000 individuals [9], this process was accompanied by almost half of ancestral loss of genetic variation and high deleterious mutation load. We furthermore show how genetic drift coupled to inbreeding following the population bottleneck has largely purged the ancient polymorphisms from the current population. In conclusion, we demonstrate the unique promise of exploiting genomic information held within museum samples for conservation and ecological research.© 2018 The Author(s). Published by Elsevier Ltd. This is an open access article available to all published under a Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0). The attached file is the published pdf

    Dense sampling of bird diversity increases power of comparative genomics

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    © 2020, The Author(s). Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1–4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families—including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species

    Robust Impulsive Stabilization of Uncertain Nonlinear Singular Systems with Application to Transportation Systems

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    We consider the robust asymptotical stabilization problem for uncertain singular systems. We design a new impulsive control technique to ensure that the controlled singular system is robustly asymptotically stable and hence derive the corresponding stability criteria. These sufficient conditions are expressed in the form of algebra matrix inequalities and can be implemented numerically. We finally provide a numerical example of a transportation system to illustrate the effectiveness and usefulness of the proposed criteria
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