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  1. Article ; Online: TP63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis

    Chengzi Huang / Simin Zhao / Yajuan Yang / Ting Guo / Hanni Ke / Xin Mi / Yingying Qin / Zi-Jiang Chen / Shidou Zhao

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 5

    Abstract: The transcription factor p63 guards genome integrity in the female germline, and its mutations have been reported in patients with premature ovarian insufficiency (POI). However, the precise contribution of the TP63 gene to the pathogenesis of POI needs ... ...

    Abstract The transcription factor p63 guards genome integrity in the female germline, and its mutations have been reported in patients with premature ovarian insufficiency (POI). However, the precise contribution of the TP63 gene to the pathogenesis of POI needs to be further determined. Here, in 1,030 Chinese patients with POI, we identified 6 heterozygous mutations of the TP63 gene that impaired the C-terminal transactivation-inhibitory domain (TID) of the TAp63α protein and resulted in tetramer formation and constitutive activation of the mutant proteins. The mutant proteins induced cell apoptosis by increasing the expression of apoptosis-inducing factors in vitro. We next introduced a premature stop codon and selectively deleted the TID of TAp63α in mice and observed rapid depletion of the p63+/ΔTID mouse oocytes through apoptosis after birth. Finally, to further verify the pathogenicity of the mutation p.R647C in the TID that was present in 3 patients, we generated p63+/R647C mice and also found accelerated oocyte loss, but to a lesser degree than in the p63+/ΔTID mice. Together, these findings show that TID-related variants causing constitutive activation of TAp63α lead to POI by inducing oocyte apoptosis, which will facilitate the genetic diagnosis of POI in patients and provide a potential therapeutic target for extending female fertility.
    Keywords Genetics ; Reproductive biology ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Acetylshikonin inhibits inflammatory responses and Papain-like protease activity in murine model of COVID-19

    Ning Lu / Tingxuan Gu / Xueli Tian / Simin Zhao / Guoguo Jin / Fredimoses Mangaladoss / Yan Qiao / Kangdong Liu / Ran Zhao / Zigang Dong

    Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-

    2022  Volume 3

    Keywords Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners

    Simin Zhao / Baisong Zheng / Liuli Wang / Wenzhe Cui / Chunlai Jiang / Zhuo Li / Wenying Gao / Wenyan Zhang / Yanjie Yin

    Chinese Medical Journal, Vol 135, Iss 22, Pp 2706-

    2022  Volume 2717

    Abstract: Abstract. Background:. Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection ... ...

    Abstract Abstract. Background:. Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated. Methods:. Immunoblotting, real-time polymerase chain reaction, in vivo/in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4+ T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data). Results:. The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression (r = 0.5110) and CD4+ T-cell counts (r = 0.5083) in HIV-1-infected patients. Conclusions:. USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.
    Keywords Medicine ; R
    Subject code 570
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Wolters Kluwer
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Identification of the candidate gene controlling tiller angle in common wheat through genome-wide association study and linkage analysis

    Lei Zhao / Canguan Wang / Tongzhu Wang / Jinyuan Liu / Qi Qiao / Yulu Yang / Pengyu Hu / Leilei Zhang / Simin Zhao / Daiying Chen / Yan Ren / Ning Zhang / Zhongdong Dong / Feng Chen

    Crop Journal, Vol 11, Iss 3, Pp 870-

    2023  Volume 877

    Abstract: Wheat tiller angle (TA) is an important agronomic trait that contributes to grain production by affecting plant architecture. It also plays a crucial role in high-yield wheat breeding. An association panel and a recombinant inbred line (RIL) population ... ...

    Abstract Wheat tiller angle (TA) is an important agronomic trait that contributes to grain production by affecting plant architecture. It also plays a crucial role in high-yield wheat breeding. An association panel and a recombinant inbred line (RIL) population were used to map quantitative trait loci (QTL) for TA. Results showed that 470 significant SNPs with 10.4%–28.8% phenotypic variance explained (PVE) were detected in four replicates by a genome-wide association study (GWAS). Haplotype analysis showed that the TA_Hap_4B1 locus on chromosome 4B was a major QTL to regulate wheat TA. Ten QTL were totally detected by linkage mapping with the RIL population, and QTA.hau-4B.1 identified in six environments with the PVE of 7.88%–18.82% was a major and stable QTL. A combined analysis demonstrated that both TA_Hap_4B1 and QTA.hau-4B.1 were co-located on the same region. Moreover, QTA.hau-4B.1 was confirmed by bulked segregant RNA-Seq (BSR-Seq) analysis. Phenotypic analysis showed that QTA.hau-4B.1 was also closely related to yield traits. Furthermore, TraesCS4B02G049700 was considered as a candidate gene through analysis of gene sequence and expression. This study can be potentially used in cloning key genes modulating wheat tillering and provides valuable genetic resources for improvement of wheat plant architecture.
    Keywords Common wheat ; Tiller angle ; GWAS ; Linkage mapping ; Plant architecture ; Agriculture ; S ; Agriculture (General) ; S1-972
    Subject code 580
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher KeAi Communications Co., Ltd.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Spatial transcriptomics analysis of esophageal squamous precancerous lesions and their progression to esophageal cancer

    Xuejiao Liu / Simin Zhao / Keke Wang / Liting Zhou / Ming Jiang / Yunfeng Gao / Ran Yang / Shiwen Yan / Wen Zhang / Bingbing Lu / Feifei Liu / Ran Zhao / Wenting Liu / Zihan Zhang / Kangdong Liu / Xiang Li / Zigang Dong

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 20

    Abstract: Abstract Esophageal squamous precancerous lesions (ESPL) are the precursors of esophageal squamous cell carcinoma (ESCC) including low-grade and high-grade intraepithelial neoplasia. Due to the absence of molecular indicators, which ESPL will eventually ... ...

    Abstract Abstract Esophageal squamous precancerous lesions (ESPL) are the precursors of esophageal squamous cell carcinoma (ESCC) including low-grade and high-grade intraepithelial neoplasia. Due to the absence of molecular indicators, which ESPL will eventually develop into ESCC and thus should be treated is not well defined. Indicators, for predicting risks of ESCC at ESPL stages, are an urgent need. We perform spatial whole-transcriptome atlas analysis, which can eliminate other tissue interference by sequencing the specific ESPL regions. In this study, the expression of TAGLN2 significantly increases, while CRNN expression level decreases along the progression of ESCC. Additionally, TAGLN2 protein level significantly increases in paired after-progression tissues compared with before-progression samples, while CRNN expression decreases. Functional studies suggest that TAGLN2 promotes ESCC progression, while CRNN inhibits it by regulating cell proliferation. Taken together, TAGLN2 and CRNN are suggested as candidate indicators for the risk of ESCC at ESPL stages.
    Keywords Science ; Q
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: The TGF-β pathway plays a key role in aortic aneurysms.

    Tingting, Tang / Wenjing, Fan / Qian, Zeng / Hengquan, Wan / Simin, Zhao / Zhisheng, Jiang / Shunlin, Qu

    Clinica chimica acta; international journal of clinical chemistry

    2019  Volume 501, Page(s) 222–228

    Abstract: Aortic dissection and aortic aneurysms are currently among the most high-risk cardiovascular diseases due to their rapid onset and high mortality. Although aneurysm research has been extensive, the pathogenesis remains unknown. Studies have found that ... ...

    Abstract Aortic dissection and aortic aneurysms are currently among the most high-risk cardiovascular diseases due to their rapid onset and high mortality. Although aneurysm research has been extensive, the pathogenesis remains unknown. Studies have found that the TGF-β/Smad pathway and aneurysm formation appear linked. For example, the TGF-β signaling pathway was significantly activated in aneurysm development and aortic dissection. Aneurysms are not, however, mitigated following knockdown of TGF-β signaling pathway-related genes. Incidence and mortality rate of ruptured thoracic aneurysms increase with the down-regulation of the classical TGF-β signaling pathway. In this review, we summarize recent findings and evaluate the differential role of classical and non-classical TGF-β pathways on aortic aneurysm. It is postulated that the TGF-β signaling pathway is necessary to maintain vascular function, but over-activation will promote aneurysms whereas over-inhibition will lead to bypass pathway over-activation and promote aneurysm occurrence.
    MeSH term(s) Animals ; Aortic Aneurysm/metabolism ; Humans ; Signal Transduction ; Transforming Growth Factor beta/metabolism
    Chemical Substances Transforming Growth Factor beta
    Language English
    Publishing date 2019-11-09
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 80228-1
    ISSN 1873-3492 ; 0009-8981
    ISSN (online) 1873-3492
    ISSN 0009-8981
    DOI 10.1016/j.cca.2019.10.042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The role of IL-1β in aortic aneurysm.

    Wenjing, Fan / Tingting, Tang / Qian, Zeng / Hengquan, Wan / Simin, Zhao / Agyare, Oware Kwabena / Zhisheng, Jiang / Shunlin, Qu

    Clinica chimica acta; international journal of clinical chemistry

    2020  Volume 504, Page(s) 7–14

    Abstract: Interleukin-1β (IL-1β) is a vital cytokine that plays an important role in regulating immune responses to infectious challenges and sterile insults. In addition, two endogenous inhibitors of functional receptor binding, IL-1 receptor antagonist (IL-1Ra), ...

    Abstract Interleukin-1β (IL-1β) is a vital cytokine that plays an important role in regulating immune responses to infectious challenges and sterile insults. In addition, two endogenous inhibitors of functional receptor binding, IL-1 receptor antagonist (IL-1Ra), complete the family. To gain biological activity, IL-1β requires processing by the protease caspase-1 and activation of inflammasomes. Numerous clinical association studies and experimental approaches have implicated members of the IL-1 family, their receptors, or components of the processing machinery in the underlying processes of cardiovascular diseases. Here, we summarize the current state of knowledge regarding the pro-inflammatory and disease-modulating role of the IL-1 family in aneurysm. We discuss clinical evidence, signalling pathway, and mechanism of action and last, lend a perspective on currently developing therapeutic strategies involving IL-1β in aneurysm.
    MeSH term(s) Aortic Aneurysm ; Caspase 1 ; Cytokines ; Humans ; Inflammasomes ; Interleukin-1beta
    Chemical Substances Cytokines ; Inflammasomes ; Interleukin-1beta ; Caspase 1 (EC 3.4.22.36)
    Language English
    Publishing date 2020-01-13
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 80228-1
    ISSN 1873-3492 ; 0009-8981
    ISSN (online) 1873-3492
    ISSN 0009-8981
    DOI 10.1016/j.cca.2020.01.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Establishment of lung cancer patient-derived xenograft models and primary cell lines for lung cancer study

    Yanan Jiang / Jimin Zhao / Yi Zhang / Ke Li / Tiepeng Li / Xinhuan Chen / Simin Zhao / Song Zhao / Kangdong Liu / Ziming Dong

    Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-

    2018  Volume 18

    Abstract: Abstract Background The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) ...

    Abstract Abstract Background The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) models and primary cells are both used to screen therapeutic regimens for cancer. However, PDX models and primary cells from the same patient are difficult to establish. Their consistency to the original tumor tissue is not well studied. Methods 31 lung cancer patient tissues were procured to establish the lung cancer PDX models and primary cell lines. Tumor growth measurements, histological and immunohistochemistry analysis, Western blotting, EGFR and K-RAS mutation detection and gefitinib sensitive assay were performed to evaluate the characteristic of established PDX models. Immunofluorescence analysis, anchorage-independent cell growth, Western blotting and gefitinib sensitive assay were performed to assay the characteristic of established primary cell lines. The whole-exome sequencing was used to compare the characteristic of the patient’s tumor tissue, established PDX and primary cell line. Results Twenty-one lung cancer PDX models (67.74%, 21/31) and ten primary cell lines (32.25%, 10/31) were established from patients’ tumor tissues. The histology and pathological immunohistochemistry of PDX xenografts are consistent with the patients’ tumor samples. Various signal pathways were activated in different PDX models (n = 5) and primary cell lines (n = 2). EGFR mutation PDX model and primary cell line (LG1) were sensitive to gefitinib treatment. The expression of CK8/18, TTF1 and NapsinA in LG1 and LG50 primary cells were also positive. And the activated signal pathways were activated in LG1 and LG50 primary cell lines. Furthermore, the gene mutation in PDX tumor tissues and primary cell line (LG50) was consistent with the mutation in LG50 patient’s tumor tissues. Conclusion These data suggested that established lung cancer PDX models and primary cell lines ...
    Keywords Lung cancer ; Patient-derived xenograft ; Signal pathway ; Primary cell culture ; Medicine ; R
    Subject code 610 ; 616
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: The Establishment of Esophageal Precancerous Lesion Model by Using p53 Conditional Knockout Mouse in Esophageal Epithelium

    Lili Zhu / Yanyan Xu / Xinhuan Chen / Jiace Qin / Tingting Niu / Yanyan Zhu / Yanan Jiang / Simin Zhao / Kangdong Liu / Jing Lu / Ge Jin / Junfen Ma / Ziming Dong / Jimin Zhao

    BioMed Research International, Vol

    2020  Volume 2020

    Abstract: Understanding the molecular mechanisms of precancerous lesion of esophageal cancer is beneficial for early diagnosis and early treatment. The deletion of p53 gene is common in esophageal cancer, but its pathogenesis is still unclear. An animal model is ... ...

    Abstract Understanding the molecular mechanisms of precancerous lesion of esophageal cancer is beneficial for early diagnosis and early treatment. The deletion of p53 gene is common in esophageal cancer, but its pathogenesis is still unclear. An animal model is urgently needed to study the mechanisms of esophageal cancer and p53 deficiency. KO mice (p53flox/flox.ED-L2-Cre+/−) and the corresponding control Loxp mice (p53flox/flox.ED-L2-Cre−/−) were obtained by crossing between the p53flox/flox mice and ED-L2-Cre+/− mice. Methylbenzylnitrosamine (NMBA) was injected subcutaneously to induce esophageal precancerous lesion of these two groups of mice. Hematoxylin and eosin staining analysis was performed to evaluate the number and extent of esophageal precancerous lesions in KO mice and Loxp mice at the 16th and 48th weeks. Immunohistochemistry analysis was used to detect the change of Ki67, P21, Bcl-2, and Bax proteins. The number and extent of esophageal precancerous lesions in KO mice were significantly increased compared with the control at the 16th and 48th weeks under the induction of NMBA. The Ki67, P21, Bcl-2, and Bax proteins also had cancer-related pathological characteristics. These results suggest that the esophageal precancerous lesion model was established under the combined effect of p53 gene deletion in esophageal epithelium and NMBA, which could provide a new esophageal precancerous lesion model to explore the mechanism of precancerous lesions.
    Keywords Medicine ; R
    Subject code 616
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: A microfluidic platform for high-purity separating circulating tumor cells at the single-cell level

    Wang, Kun / Lin Zhou / Simin Zhao / Zule Cheng / Shihui Qiu / Yunxing Lu / Zhenhua Wu / Abdel Hady A. Abdel Wahab / Hongju Mao / Jianlong Zhao

    Talanta. 2019 Aug. 01, v. 200

    2019  

    Abstract: Circulating tumor cells (CTCs) are rare cancer cells that are shed from the tumors into the peripheral blood and are instrumental in distant metastasis. Early detection of CTCs can therefore improve prognoses and help design patient-specific treatment ... ...

    Abstract Circulating tumor cells (CTCs) are rare cancer cells that are shed from the tumors into the peripheral blood and are instrumental in distant metastasis. Early detection of CTCs can therefore improve prognoses and help design patient-specific treatment regimen. However, the current CTC isolation techniques have poor efficacy and selectivity, owing to the rarity and heterogeneity of the CTCs. We designed a microchip for integrated single-cell isolation of CTCs – based on cell size and immuno-phenotype – and analysis. Each isolation unit consisted of a trap channel, a bypass channel, and a release channel. The larger cells were preferentially captured at the trap channels and flushed out selectively via release microvalves according to their immuno-phenotype. The average recovery rate and purity of lung cancer cells isolated from a spiked WBC population were respectively 92.5% and 94% using the microchip, which were significantly higher compared to that obtained using anti-CD45 magnetic beads. In addition, the isolated cancer cells were analyzed on chip for the surface markers of epithelial mesenchymal transition. Taken together, the integrated microchip is a promising tool for the isolation and analysis of CTCs in the clinical setting.
    Keywords epithelium ; isolation techniques ; leukocytes ; magnetism ; metastasis ; microchip technology ; neoplasm cells ; neoplasms
    Language English
    Dates of publication 2019-0801
    Size p. 169-176.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1500969-5
    ISSN 1873-3573 ; 0039-9140
    ISSN (online) 1873-3573
    ISSN 0039-9140
    DOI 10.1016/j.talanta.2019.03.035
    Database NAL-Catalogue (AGRICOLA)

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