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Novel lysosome-targeted anticancer fluorescent agents used in zebrafish and nude mouse tumour imaging

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 112-120 doi: 10.1007/s11705-021-2075-5

摘要： The design of three novel fatty nitrogen mustard-based anticancer agents with fluorophores incorporated into the alkene structure (CXL 118, CXL121, and CXL122) is described in this report. The results indicated that these compounds are selectively located in lysosomes and exhibit effective antitumour activity. Notably, these compounds can directly serve as both reporting and imaging agents in vitro and in vivo without the need to add other fluorescent tagging agents.

关键词： fluorescent drug     lysosomal     anticancer     zebrafish     nude-mouse tumour imaging    

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A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 108-111 doi: 10.1007/s11684-014-0344-0

摘要：

Hemoperitoneum is a rare and potentially life-threatening complication of GIST. We reported a 54-year-old man who developed disseminated intra-abdominal recurrence from a previously resected gastrointestinal stromal tumour (GIST) of the small bowel, and the patient presented with hemoperitoneum. Emergent debulking surgery was performed. A high dose imatinib was prescribed. Despite the presence of residual disease, the patient was well clinically 8 months after the operation. Even though, there is no evidence to support the routine use of debulking surgery in the management of GIST. In our patient, disease progression after second line targeted therapy and the absence of alternative treatment options for spontaneous rupture and hemoperitoneum prompted us to treat the patient aggressively. Resection of the ruptured GIST was carried out for control of bleeding and to prevent recurrent bleeding in this patient with good surgical risks. During the treatment decision-making, the patient’s general condition, the risk of surgery and the extent of dissemination were taken into consideration. In this patient who presented with spontaneous rupture of a small intestinal GIST, the novel use of targeted therapy and aggressive surgical treatment produced reasonably good survival outcome.

关键词： gastrointestinal stromal tumour     hemoperitoneum     small bowel GIST     small bowel neoplasm     imatinib    

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Chemotactic effect of urokinase-type plasminogen activator on mouse spermatozoa

DING Xiaofang, LI Honggang, XIONG Chengliang

《医学前沿（英文）》 2008年 第2卷 第2期   页码 195-199 doi: 10.1007/s11684-008-0037-7

摘要： The aim of this study is to investigate the chemotactic effect of urokinase-type plasminogen activator (uPA) on mouse spermatozoa. Capillary assays were applied to study the chemotactic activity of ascending and descending gradients of uPA. Firstly, the chemotactic effect of an ascending gradient of uPA on mouse spermatozoa was observed by counting the number of spermatozoa that migrated into the capillary after incubation with uPA for 5, 10, 20, and 30 min, respectively, compared with that after incubation with F10. Twenty minutes was a suitable incubation time to obtain a plateau of sperm accumulation. Meanwhile, to confirm the specific effect of uPA on mouse sperm chemotaxis, uPA inhibitor (PAI-1) and anti-uPAR rabbit IgG were added to the test solution containing 20 U/mL uPA, respectively. To exclude the possibility that PAI-1 and anti-uPAR rabbit IgG may affect sperm accumulation nonspecifically, PAI-1 and anti-uPAR rabbit IgG were added to F10, respectively. It was found that the chemotactic effect of uPA was neutralized completely by PAI-1 and anti-uPAR rabbit IgG. PAI-1 and anti-uPAR rabbit IgG had no neutralizing effect on the sperm chemotactic effect. Lastly, the sperm chemotaxis response to a descending gradient of uPA was also observed. Taken together, the results suggest that uPA can induce sperm chemotaxis by binding to its receptor on the sperm membrane and may act as a chemoattractant in precontacting sperm-egg communication thereby increasing the chance encounter of spermatozoa and eggs.

关键词： chemotactic activity     receptor     uPA inhibitor     F10     chemoattractant    

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Lack of CFAP54 causes primary ciliary dyskinesia in a mouse model and human patients

《医学前沿（英文）》 doi: 10.1007/s11684-023-0997-7

摘要： Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future.

关键词： primary ciliary dyskinesia     CFAP54     cilia    

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evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 471-476 doi: 10.1007/s11684-014-0365-8

摘要：

This work aims to estimate the value of diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) in detecting early-stage kidney injury in type 2 diabetic patients with normoalbuminuria (NAU) versus microalbuminuria (MAU) prospectively. A total of 30 T2DM patients with normal kidney function were recruited and assigned to the NAU group (n = 14) or MAU group (n= 16) according to 8 h overnight urinary albuminuria excretion rate (AER) results. A contemporary cohort of health check-up recipients were included as controls (n = 12). DWI and DTI scans were performed on bilateral kidney using SE single-shot EPI, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the renal parenchyma was determined from ADC and FA maps of the three groups. ADC and FA values were compared among the three groups. According to DWI with a b value of 400 s/mm2, the MAU and NAU groups showed significantly lowered mean ADC values compared with the healthy controls (P<0.01). The mean ADC in the MAU group [(2.22±0.07)×10–3 mm2/s] was slightly lower than that of the NAU group [(2.31±0.22)×10–3 mm2/s], but this difference was not statistically significant (P>0.05). The FA value in the MAU group was higher than that in the control group (0.45±0.07 vs. 0.39±0.03, P = 0.004) but did not differ from that in the NAU group (0.42±0.03) (P>0.05). ADC and FA values may be more sensitive than urine AER in reflecting early-stage kidney injury and, hence, may facilitate earlier detection and quantitative evaluation of kidney injury in T2DM patients. Combined evaluation of ADC and FA values may provide a better quantitative approach for identifying diabetic nephropathy at early disease stages.

关键词： type 2 diabetes mellitus     microalbuminuria     diffusion weighted imaging     diffusion tensor imaging     early-stage kidney injury    

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MiRNA-451 is a potential biomarker for estrogenicity in mouse uterus

Lingyan HOU, Yun LU, Ying LI, Li LI

《环境科学与工程前沿（英文）》 2014年 第8卷 第1期   页码 99-105 doi: 10.1007/s11783-013-0490-7

摘要： The uterotrophic assay has been commonly used to test environmental estrogens in vivo, however, it is often not sensitive enough sometimes. An alternative way is to evaluate estrogenicity through biomarker genes. MicroRNA (miRNA) is a class of regulatory gene, which has been shown to be a good biomarker for many diseases and toxicological effects in recent years, and some evidences showed that estrogen induced response was partially mediated by miRNAs. In this study, two types of microarrays were used to test the 17β-estradiol (E2) induced miRNA expression profile at different time points in the immature mouse uterus. Statistical analysis showed the aldehyde slide based array had less variation than the amino slide based array, and 11 dysregulated miRNAs were screened out for significant fold change. Real-time PCR was performed to further confirm that 4 out of 7 selected miRNAs, namely miR-451, miR-155, miR-335-5p, and miR-365, are E2 regulated miRNAs in the uterus. The function of the predicted targets of these miRNAs is involved in cell grow control, which is consistent with the main E2 function in the uterus. MiR-451 had similar strong responses to E2 in the uterus of both immature and overiectomized mice, and could be a potential biomarker for estrogenicity in the uterus.

关键词： estrogen     microRNA (miRNA)     microarray     biomarker    

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Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

《医学前沿（英文）》 2008年 第2卷 第1期   页码 51-57 doi: 10.1007/s11684-008-0010-5

摘要： To determine whether squamous cell carcinoma antigen recognized by human T cell 3 (SART3) gene can induce antitumor immunity against tumor cells which express the gene, we constructed mouse tumor cells expressing human SART3 (LM8-SART3) and carried out experiments . After subcutaneous injection with SART3 gene vaccine, cytotoxic T lymphocyte (CTL) activity was measured using Cell Counting Kit-8. As for the part, C3H mice were divided into several groups. One group was challenged with tumor cells after immunity. Another group was treated with the vaccine after tumor implantation. It was found that human SART3 DNA vaccine can elicit a specific CTL reaction from the mouse splenocytes. After vaccination, tumor occurrence and tumor growth speed was reduced. The vaccine also shows activity in tumor treatment. We conclude that the human SART3 DNA vaccine can induce antitumor ability against tumor cells expressing human SART3 (LM8-SART3) which may provide new possibilities in antitumor therapy.

关键词： antitumor therapy     occurrence     implantation     DNA vaccine     SART3 DNA    

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Molecular dynamic simulation on the conformation of mouse muscle type nAChR

Shengai SUN, Rilei YU, Yanhui ZHANG, Yanni LI,

《化学科学与工程前沿（英文）》 2010年 第4卷 第3期   页码 348-352 doi: 10.1007/s11705-009-0284-4

摘要： A mouse muscle type nAChR model ((α1)βδγ) was built based on the cryoelectron microscopic structure of intact nAChR and the high resolution crystal structure of nAChR-α1 subunit. The conformation of the pentameric nAChR model was investigated by molecular dynamic simulation. The function of water molecule in the hydrophilic interior was clarified. The reason for Tyr127 showing two alternative conformations was discussed in detail.

关键词： pentameric     hydrophilic     Tyr127     cryoelectron microscopic     conformation    

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Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 330-335 doi: 10.1007/s11684-016-0459-6

摘要：

The enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) is a histone-lysine N-methyltransferase enzyme that participates in DNA methylation. Ezh2 has also been reported to play crucial roles in stem cell proliferation and differentiation. However, the detailed expression profile of Ezh2 during mouse cochlear development has not been investigated. Here, we examined the spatiotemporal expression of Ezh2 in the cochlea during embryonic and postnatal development. Ezh2 expression began to be observed in the whole otocyst nuclei at embryonic day 9.5 (E9.5). At E12.5, Ezh2 was expressed in the nuclei of the cochlear prosensory epithelium. At E13.5 and E15.5, Ezh2 was expressed from the apical to the basal turns in the nuclei of the differentiating cochlear epithelium. At postnatal day (P) 0 and 7, the Ezh2 expression was located in the nuclei of the cochlear epithelium in all three turns and could be clearly seen in outer and inner hair cells, supporting cells, the stria vascularis, and spiral ganglion cells. Ezh2 continued to be expressed in the cochlear epithelium of adult mice. Our results provide the basic Ezh2 expression pattern and might be useful for further investigating the detailed role of Ezh2 during cochlear development.

关键词： polycomb repressive complex     Ezh2     expression     inner ear     cochlea     development    

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Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing

《医学前沿（英文）》 2022年 第16卷 第6期   页码 919-931 doi: 10.1007/s11684-021-0918-6

摘要： Preeclampsia (PE) is characterized by placenta-mediated pregnancy complication. The only effective treatment for PE is the delivery of the placenta. However, this treatment may cause preterm birth and neonatal death. Therefore, preventing PE is needed. The mechanism of PE involves abnormal placentation, which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation. These mediators contribute to systemic vascular dysfunction, inflammatory responses, and excessive thrombin generation. Microparticles (MPs) are reportedly involved in PE by promoting the thromboinflammatory response. This study describes a strategy to prevent PE by reducing MP release using the recombinant protein, diannexin. Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation. Additionally, diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells. Moreover, in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice. Furthermore, diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro. These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.

关键词： preeclampsia     recombinant protein diannexin     microparticle     NLRP3 inflammasome     phosphatidylserin    

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Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

《化学科学与工程前沿（英文）》 2023年 第17卷 第3期   页码 298-306 doi: 10.1007/s11705-022-2212-9

摘要： Herein, a reversible pH fluorescent sensor was developed using caffeic acid as the precursor by one-step solvothermal synthesis method. The carbon dots-based sensor (CA-CDs) exhibited pH-dependent increase in fluorescence intensity and showed linear relationship in the range of pH 6.60 and 8.00. Notably, the fluorescence sensor has a reversible response to pH change. Finally, the CA-CDs has been successfully applied for two-photon imaging of the pH in liver and kidney of diabetic mice. Imaging results showed that the pH value in kidney of diabetic mice was lower than that of the normal mice, while the pH value in liver of diabetic mice was almost the same as that of the normal mice. The present study provides a simple analytical method for pH detection suitable for in vivo.

关键词： carbon dots     two-photon imaging     pH     diabetic mice    

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In vivo imaging of hematopoietic stem cell development in the zebrafish

Panpan Zhang, Feng Liu

《医学前沿（英文）》 2011年 第5卷 第3期   页码 239-247 doi: 10.1007/s11684-011-0123-0

摘要： imaging is crucial for developmental biology and can further help to follow cell development/differentiation in normal and pathological conditions. Recent advances in optical imaging techniques has facilitated tracing of the developmental dynamics of a specific organ, tissue, or even a single cell. The zebrafish is an excellent model for imaging of hematopoiesis due to its transparent embryo at early stage; moreover, different zebrafish hematopoietic stem cells (HSCs) transgenic lines have been demonstrated as very useful tools for illustrating the details of the HSC developmental process. In this review, we summarize recent studies related to the non-invasive imaging of HSC transgenics, to show that zebrafish transgenic lines are powerful tools for developmental biology and disease. At the end of the review, the perspective and some open questions in this field will be discussed.

关键词： hematopoietic stem cell     hematopoiesis     in vivo imaging     transgenics     zebrafish    

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Histone variants: critical determinants in tumour heterogeneity

Tao Wang, Florent Chuffart, Ekaterina Bourova-Flin, Jin Wang, Jianqing Mi, Sophie Rousseaux, Saadi Khochbin

《医学前沿（英文）》 2019年 第13卷 第3期   页码 289-297 doi: 10.1007/s11684-018-0667-3

摘要： Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

关键词： cancer-testis     TH2B     TH2A     H1T     H1.0     H1F0     linker histones    

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Construction of lentiviral vector carrying Rab9 gene and its expression in mouse brain

Youguo HAO, Min ZHANG, Jinzhi XU, Bitao BU, Jiajun WEI

《医学前沿（英文）》 2009年 第3卷 第2期   页码 141-147 doi: 10.1007/s11684-009-0041-6

摘要： Rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. Rab9 mediates late endosome-to- -Golgi-network trafficking. To explore the possibility of Rab9-related gene therapy for neurodegenerative diseases, we packed Lentivirus encoding Rab9. The expressing plasmid pCDH1-MCF1-Rab9-EF1-copGFP was constructed by using molecular biological techniques. The Lentivirus encoding Rab9 cDNA was packed by Lifectamine-2000 mediated co-transfection of the plasmid pPACKH1- , pPACKH1- and pVSV- into 293T cells. DNA sequencing proved the successful construction of pCDH1-MCF1-Rab9-EF1-copGFP. After 72 hours, the expression of GFP could be detected in BV-2 cells. Western blotting revealed that the Rab9 gene expression in BALB/c mice brain was up-regulated significantly 4 weeks after injection with Lentivirus encoding Rab9, which evidenced a satisfactory increasing effect of this virus. Administration of Lenti-Rab9 to postnatal day 3 Niemann-Pick disease type C (NPC) mice reduced motor defects and prevented the weight loss associated with female NPC mice, as well as modulating the death rate of Purkinje neurons. It is concluded that the packaging of Lentivirus encoding Rab9 was successful. Lentivirus encoding Rab9 can increase the expression of Rab9 gene effectively, which might offer a novel means for the treatment of neurodegenerative diseases.

关键词： Rab9     lentivirus     gene therapy     gene transfer    

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Anefficient quadrature demodulator for medical ultrasound imaging

Hao ZHOU,Yin-fei ZHENG

《信息与电子工程前沿（英文）》 2015年 第16卷 第4期   页码 301-310 doi: 10.1631/FITEE.1400205

摘要： Quadrature demodulation is used in medical ultrasound imaging to derive the envelope and instantaneous phase of the received radio-frequency (RF) signal. In quadrature demodulation, RF signal is multiplied with the sine and cosine wave reference signal and then low-pass filtered to produce the base-band complex signal, which has high computational complexity. In this paper, we propose an efficient quadrature demodulation method for B-mode and color flow imaging, in which the RF signal is demodulated by a pair of finite impulse response filters without mixing with the reference signal, to reduce the computational complexity. The proposed method was evaluated with simulation and in vivo experiments. From the simulation results, the proposed quadrature demodulation method produced similar normalized residual sum of squares (NRSS) and velocity profile compared with the conventional quadrature demodulation method. In the in vivo color flow imaging experiments, the time of the demodulation process was 5.66 ms and 3.36 ms, for the conventional method and the proposed method, respectively. These results indicated that the proposed method can maintain the performance of quadrature demodulation while reducing computational complexity.

关键词： B-mode ultrasound imaging     Color flow imaging     Quadrature demodulation     Finite impulse response filter    

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标题 作者 时间 类型 操作

Novel lysosome-targeted anticancer fluorescent agents used in zebrafish and nude mouse tumour imaging

期刊论文

A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

期刊论文

Chemotactic effect of urokinase-type plasminogen activator on mouse spermatozoa

DING Xiaofang, LI Honggang, XIONG Chengliang

期刊论文

Lack of CFAP54 causes primary ciliary dyskinesia in a mouse model and human patients

期刊论文

evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2

null

期刊论文

MiRNA-451 is a potential biomarker for estrogenicity in mouse uterus

Lingyan HOU, Yun LU, Ying LI, Li LI

期刊论文

Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

期刊论文

Molecular dynamic simulation on the conformation of mouse muscle type nAChR

Shengai SUN, Rilei YU, Yanhui ZHANG, Yanni LI,

期刊论文

Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium

null

期刊论文

Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing

期刊论文

Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

期刊论文

In vivo imaging of hematopoietic stem cell development in the zebrafish

Panpan Zhang, Feng Liu

期刊论文

Histone variants: critical determinants in tumour heterogeneity

Tao Wang, Florent Chuffart, Ekaterina Bourova-Flin, Jin Wang, Jianqing Mi, Sophie Rousseaux, Saadi Khochbin

期刊论文

Construction of lentiviral vector carrying Rab9 gene and its expression in mouse brain

Youguo HAO, Min ZHANG, Jinzhi XU, Bitao BU, Jiajun WEI

期刊论文

Anefficient quadrature demodulator for medical ultrasound imaging

Hao ZHOU,Yin-fei ZHENG

期刊论文