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- Feng, Tongbao, et al.
(author)
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miR-124 downregulation leads to breast cancer progression via LncRNA-MALAT1 regulation and CDK4/E2F1 signal activation.
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:13, s. 16205-16216
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Journal article (peer-reviewed)abstract
- The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recently shown to be dysregulated in several cancers. However, the mechanisms underlying the role of MALAT1 in breast cancer remain unclear. Herein, we showed that MALAT1 was aberrantly increased in breast cancer tissues and cells. MALAT1-siRNA inhibited breast cancer cell proliferation and cell cycle progression in vitro and in vivo. Furthermore, MALAT1 acted as an endogenous potent regulator by directly binding to miR-124 and down-regulating miR-124 expression. In addition, MALAT1 reversed the inhibitory effect of miR-124 on breast cancer proliferation and was involved in the cyclin-dependent kinase 4 (CDK4) expression. Taken together, our data highlight the pivotal role of MALAT1 in breast cancer tumorigenesis. Moreover, the present study elucidated the MALAT1-miR-124-CDK4/E2F1 signaling pathway in breast cancer, which might provide a new approach for tackling breast cancer.
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| 2. |
- Groenewold, Nynke A., et al.
(author)
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Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group
- 2023
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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089
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Journal article (peer-reviewed)abstract
- There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
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| 4. |
- Sang, Shaowei, et al.
(author)
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The epidemiological characteristics of dengue in high-risk areas of China, 2013-2016
- 2021
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In: PLoS Neglected Tropical Diseases. - : Public Library of Science. - 1935-2727 .- 1935-2735. ; 15:12
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Journal article (peer-reviewed)abstract
- Introduction: Dengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and longitudinal epidemiological characteristics and the evolutionary dynamics of dengue in high-risk areas of China is limited.Methods: Records of dengue cases from 2013 to 2016 were obtained from the China Notifiable Disease Surveillance System. Full envelope gene sequences of dengue viruses detected from the high-risk areas of China were collected. Maximum Likelihood tree and haplotype network analyses were conducted to explore the phylogenetic relationship of viruses from high-risk areas of China.Results: A total of 56,520 cases was reported in China from 2013 to 2016. During this time, Yunnan, Guangdong and Fujian provinces were the high-risk areas. Imported cases occurred almost year-round, and were mainly introduced from Southeast Asia. The first indigenous case usually occurred in June to August, and the last one occurred before December in Yunnan and Fujian provinces but in December in Guangdong Province. Seven genotypes of DENV 1-3 were detected in the high-risk areas, with DENV 1-I the main genotype and DENV 2-Cosmopolitan the secondary one. The Maximum Likelihood trees show that almost all the indigenous viruses separated into different clusters. DENV 1-I viruses were found to be clustered in Guangdong Province, but not in Fujian and Yunnan, from 2013 to 2015. The ancestors of the Guangdong viruses in the cluster in 2013 and 2014 were most closely related to strains from Thailand or Singapore, and the Guangdong virus in 2015 was most closely related to the Guangdong virus of 2014. Based on closest phylogenetic relationships, viruses from Myanmar possibly initiated further indigenous cases in Yunnan, those from Indonesia in Fujian, while viruses from Thailand, Malaysia, Singapore and Indonesia were predominant in Guangdong Province.Conclusions: Dengue is still an imported disease in China, although some genotypes continued to circulate in successive years. Viral phylogenies based on the envelope gene suggested periodic introductions of dengue strains into China, primarily from Southeast Asia, with occasional sustained, multi-year transmission in some regions of China.Author summary: Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease globally. Because of the multiple introductions, dengue outbreaks occurred in epidemic seasons in Southern China, supported by suitable weather conditions. Surveillance data from 2013 to 2016 in China showed that Guangdong, Yunnan and Fujian provinces were the high-risk areas, with dengue outbreaks occurring almost every year. However, knowledge has been lacking of the epidemiological characteristics and the evolution pattern of dengue virus in these high-risk areas. This study shows a variety of epidemiological characteristics and sources of imported cases among the high-risk areas in China, with likely origins primarily from countries in Southeast Asia. Seven genotypes of the DENV 1-3 variety co-circulated with DENV1-I, the main genotype, and DENV 2-Cosmopolitan, the secondary. Genetic relationships among viral strains suggest that the indigenous viruses in the high-risk areas arose from imported viruses and sometimes persisted between years into the next epidemic season, especially in Guangdong Province. Population movement has played a vital role in dengue epidemics in China. This information may be useful in dengue control, especially during epidemic seasons and in the development of an early warning system within the region, in collaboration with bordering countries.
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| 5. |
- Sang, Shaowei, et al.
(author)
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The evolutionary dynamics of DENV 4 genotype I over a 60-year period
- 2019
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In: PLoS Neglected Tropical Diseases. - : Public Library of Science. - 1935-2727 .- 1935-2735. ; 13:7
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Journal article (peer-reviewed)abstract
- Dengue virus serotype 4 (DENV 4) has had a relatively low prevalence worldwide for decades; however, likely due to data paucity, no study has investigated the epidemiology and evolutionary dynamics of DENV 4 genotype I (DENV 4-I). This study aims to understand the diversity, epidemiology and dynamics of DENV 4-I. We collected 404 full length DENV4-1 envelope (E) gene sequences from 14 countries using two sources: Yunnan Province in China (15 strains during 2013-2016) and GenBank (489 strains up to 2018-01-11). Conducting phylogenetic and phylogeographical analyses, we estimated the virus spread, population dynamics, and selection pressures using different statistical analysis methods (substitution saturation, likelihood mapping, Bayesian coalescent inference, and maximum likelihood estimation). Our results show that during the last 60 years (1956-2016), DENV 4-I was present in mainland and maritime Southeast Asia, the Indian subcontinent, the southern provinces of China, parts of Brazil and Australia. The recent spread of DENV 4-I likely originated in the Philippines and later spread to Thailand. From Thailand, it spread to adjacent countries and eventually the Indian subcontinent. Apparently diverging around years 1957, 1963, 1976 and 1990, the different Clades (Clade I-V) were defined. The mean overall evolution rate of DENV 4-I was 9.74 (95% HPD: 8.68-10.82) x 10(-4) nucleotide substitutions/site/year. The most recent common ancestor for DENV 4-I traces back to 1956. While the demographic history of DENV 4-I fluctuated, peaks appeared around 1982 and 2006. While purifying selection dominated the majority of E-gene evolution of DENV 4-I, positive selection characterized Clade III (Vietnam). DENV 4-I evolved in situ in Southeast Asia and the Indian subcontinent. Thailand and Indian acted as the main and secondary virus distribution hubs globally and regionally. Our phylogenetic analysis highlights the need for strengthened regional cooperation on surveillance and sharing of sample sequences to improve global dengue control and cross-border transmission prevention efforts. Author summary Dengue virus (DENV) can be classified into four serotypes, DENV 1, 2, 3 and 4. Although DENV 4 is the first dengue serotype to diverge in phylogenetic analyses of the genus Flavivirus, this serotype occurs at a low prevalence worldwide and spreads the least rapidly. Similar to other serotypes, DENV 4 can also cause severe dengue (SD) disease manifestations, such as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). To date, no study has investigated the epidemiology and dynamics of DENV 4 genotype I comprehensively. In this study, we seek to address this gap. Our study shows that the distribution of DENV 4-I is mainly restricted to Southeast Asia and the Indian subcontinent. The most recent spread of DENV 4-I likely originated from Southeast Asia-initially circulating in the Philippines, then Thailand and later on the Indian subcontinent. Viruses evolved in situ in Southeast Asia and the Indian subcontinent, respectively. Although DENV 4-I occasionally spread elsewhere, this genotype did not become widely established. The overall evolution rate of DENV 4-I was comparable with that of DENV 2-4. The nucleotide sequences indicates that the demographic history of DENV 4-I fluctuated with peaks apparent during parts of the 1980s and 2000s. Although a weak positive selection existed in Clade III -predominately in Vietnam, purifying selection dominated the E-gene evolution of DENV 4-I.
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