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Influence of retinoic acid on TBX1 expression in myocardial cells induced by Shh and Fgf8

Miao LIU, Xiaoyan WU, Jiawei XU, Runming JIN

《医学前沿（英文）》 2009年第3卷第1期页码 61-66 doi: 10.1007/s11684-009-0007-8

摘要： The aim of this study was to explore the regulatory mechanism of retinoic acid (RA) on the TBX1 gene expression in myocardial cells. Ventricular cardiocytes were isolated from neonatal rats and cultured, and then treated with different concentrations of retinoic acid. The expression of Shh and Fgf8 at mRNA and protein levels in neonatal rat myocardial cells were measured by using RT-PCR and Western blot technique, respectively. There was basal expression of Shh and Fgf8 in the control group. When treated with 3×10 mol/L RA, we observed that the expression of Shh mRNA and protein in neonatal rat myocardial cells were up-regulated by 1.51 ( <0.05) and 1.10 times ( <0.05), respectively. In comparison with the control group, under the concentration of 5×10 mol/L RA, they were up-regulated by 2.21 ( <0.05) and 2.38 times ( <0.05) individually. Meanwhile, we could detect that the expression of Fgf8 mRNA and protein were up-regulated by 2.50 times ( <0.05) and 80% ( <0.05) separately compared with the control group after stimulation of 3×10 mol/L RA, and they were up-regulated by 3.48 ( <0.05) and 2.04 times ( <0.05) individually after stimulation of 5×10 mol/L RA. The results indicated that RA could induce the expression of Shh and Fgf8 in neonatal rat myocardial cells. At the same time, it has shown that Shh and Fgf8 were involved in the regulation process of RA on TBX1 expression.

关键词： retinoic acid Tbx1 protein Shh protein Fgf8 protein

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The FGF metabolic axis

Xiaokun Li

《医学前沿（英文）》 2019年第13卷第5期页码 511-530 doi: 10.1007/s11684-019-0711-y

摘要： Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural elements that enable functional divergence and specification. Heparan sulfate-binding FGFs, which play critical roles in embryonic development and adult tissue remodeling homeostasis, adapt to an autocrine/paracrine mode of action to promote cell proliferation and population growth. By contrast, FGF19, 21, and 23 coevolve through losing binding affinity for extracellular matrix heparan sulfate while acquiring affinity for transmembrane α-Klotho (KL) or β-KL as a coreceptor, thereby adapting to an endocrine mode of action to drive interorgan crosstalk that regulates a broad spectrum of metabolic homeostasis. FGF19 metabolic axis from the ileum to liver negatively controls diurnal bile acid biosynthesis. FGF21 metabolic axes play multifaceted roles in controlling the homeostasis of lipid, glucose, and energy metabolism. FGF23 axes from the bone to kidney and parathyroid regulate metabolic homeostasis of phosphate, calcium, vitamin D, and parathyroid hormone that are important for bone health and systemic mineral balance. The significant divergence in structural elements and multiple functional specifications of FGF19, 21, and 23 in cellular and organismal metabolism instead of cell proliferation and growth sufficiently necessitate a new unified and specific term for these three endocrine FGFs. Thus, the term “FGF Metabolic Axis,” which distinguishes the unique pathways and functions of endocrine FGFs from other autocrine/paracrine mitogenic FGFs, is coined.

关键词： FGF19 FGF21 FGF23 FGFR metabolism endocrine Klotho

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FGF23 associated bone diseases

null

《医学前沿（英文）》 2013年第7卷第1期页码 65-80 doi: 10.1007/s11684-013-0254-6

摘要：

Recently, fibroblast growth factor 23 (FGF23) has sparked widespread interest because of its potential role in regulating phosphate and vitamin D metabolism. In this review, we summarized the FGF superfamily, the mechanism of FGF23 on phosphate and vitamin D metabolism, and the FGF23 related bone disease.

关键词： fibroblast growth factor 23 FGF receptor phosphate metabolism Klotho bone disease

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FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

《医学前沿（英文）》 2022年第16卷第6期页码 896-908 doi: 10.1007/s11684-022-0944-z

摘要： Fibroblast growth factor 13 (FGF13) is aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in the development of acute myeloid leukemia (AML) and emphasize its associations with bone marrow niches. Results showed that FGF13 was lowly expressed in patients with AML and that its elevated expression was related to prolonged overall survival (OS). Univariate and multivariate Cox regression analyses identified FGF13 as an independent prognostic factor. A prognostic nomogram integrating FGF13 and clinicopathologic variables was constructed to predict 1-, 3-, and 5-year OS. Gene mutation and functional analyses indicated that FGF13 was not associated with AML driver mutations but was related to bone marrow niches. As for immunity, FGF13 was remarkably associated with T cell count, immune checkpoint genes, and cytokines. In addition, FGF13 overexpression substantially inhibited the growth and significantly induced the early apoptosis of AML cells. The xenograft study indicated that FGF13 overexpression prolonged the survival of recipient mice. Overall, FGF13 could serve as an independent prognostic factor for AML, and it was closely related to the bone marrow microenvironment.

关键词： acute myeloid leukemia FGF13 prognosis immune-related genes bone marrow niches

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Zeolitic imidazolate framework-8 (ZIF-8) for drug delivery: A critical review

Simin Feng, Xiaoli Zhang, Dunyun Shi, Zheng Wang

《化学科学与工程前沿（英文）》 2021年第15卷第2期页码 221-237 doi: 10.1007/s11705-020-1927-8

摘要： Zeolitic imidazolate framework-8 (ZIF-8), composed of Zn ions and imidazolate ligands, is a class of metal-organic frameworks, which possesses a similar structure as conventional aluminosilicate zeolites. This material exhibits inherent porous property, high loading capacity, and pH-sensitive degradation, as well as exceptional thermal and chemical stability. Extensive research effort has been devoted to relevant research aspects ranging from synthesis methods, property characterization to potential applications of ZIF-8. This review focuses on the recent development of ZIF-8 synthesis methods and its promising applications in drug delivery. The potential risks of using ZIF-8 for drug delivery are also summarized.

关键词： zeolitic imidazolate framework-8 (ZIF-8) synthesis methods applications drug delivery

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Role of salivary matrix metalloproteinase-8 (MMP-8) in chronic periodontitis diagnosis

null

《医学前沿（英文）》 2015年第9卷第1期页码 72-76 doi: 10.1007/s11684-014-0347-x

摘要：

Periodontitis is an inflammatory disease of the periodontium. Any imbalance between the matrix metalloproteinases (MMPs) secreted by neutrophils and tissue inhibitors initiates the destruction of collagen in gum tissue, leading to chronic periodontitis. This study aimed to correlate salivary levels of MMP-8 and periodontal parameters of chronic periodontitis to establish MMP-8 as a noninvasive marker for the early diagnosis of chronic periodontitis. The study involved 40 subjects visiting the periodontic OPD of Dr. Ziauddin Ahmad Dental College and Hospital, located in Aligarh, U.P., India, from 2011 to 2012. The subjects were divided into two groups: group I consisted of 20 periodontally healthy subjects (controls) while group II consisted of 20 patients with chronic periodontitis. Chronic periodontitis was assessed on the basis of several periodontal parameters, including pocket probing depth (PPD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI). Around 3 ml of unstimulated and whole expectorated saliva was collected for MMP-8 estimation by ELISA using Quantikine human total MMP-8 immunoassay kits. Data were analyzed using STATISTICA (Windows version 6) software. Salivary MMP-8 levels of groups I and II were 190.91±143.89 ng/ml and 348.26±202.1 ng/ml, respectively. The MMP-8 levels and periodontal status (PPD, CAL, GI, and PI) of groups I and II showed positive and significant correlations (for PPD, r = 0.63, P<0.001; for CAL, r = 0.54, P<0.001; for GI, r = 0.49, P<0.001; and for PI, r = 0.63, P<0.001). The results of this study demonstrate elevated concentrations of MMP-8 in individuals with chronic periodontitis.

关键词： matrix metalloproteinase-8 chronic periodontitis pocket probing depth clinical attachment level gingival index plaque index

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Protective efficacy of vaccination with NcMIC3 and NcMIC8 against

Taotao ZHANG, Xiao ZHANG, Qun LIU, Jianhai XU, Jing LIU

《农业科学与工程前沿（英文）》 2019年第6卷第2期页码 188-196 doi: 10.15302/J-FASE-2019253

摘要：

Microneme proteins (MICs) are important for Apicomplexan parasite invasion due to their adhesion to host cells. Several studies have indicated that MIC3 and MIC8 are important adhesion factors and potential vaccine candidates against neosporosis. In this study, we evaluated the protective efficacy of recombinant proteins and DNA vaccines of NcMIC3 and NcMIC8. BALB/c mice were immunized with rNcMIC3, rNcMIC8, pcDNA3.1-NcMIC3 and pcDNA3.1-NcMIC8 respectively, and challenged with tachyzoites. The immune responses were evaluated through cytokine, antibody measurements and the parasite burden in the mice brain tissues. Serological analysis showed that recombinant protein vaccines induced higher levels of immunoglobulin G (IgG) than other groups. The percentage of IgG1 and IgG2a in the recombinant protein groups was higher than the other groups, and with a predominance of IgG1 over IgG2a, suggesting that recombinant protein vaccines elicited a Th2-type immune response, while DNA vaccines mainly produce a Th1-type immune response. In addition, mice immunized with rNcMIC3 and rNcMIC8 a had lower parasite burden in brain tissue compared with the other groups. These results demonstrate that rNcMIC3 and rNcMIC8 could induce humoral and Th2-type immune response, leading to a considerable level of resistance against neosporosis.

关键词： NcMIC3 NcMIC8 Neospora caninum vaccination

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青岛地铁8号线海底隧道

贺维国, 刘鹏

《工程（英文）》 2018年第4卷第2期页码 167-169 doi: 10.1016/j.eng.2018.03.012

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8英寸绝缘栅双极型晶体管 (IGBT) 关键技术研究 Article

刘国友,丁荣军,罗海辉

《工程（英文）》 2015年第1卷第3期页码 361-366 doi: 10.15302/J-ENG-2015043

摘要：

基于8英寸绝缘栅双极型晶体管 (IGBT) 生产线的建设，重点解决了8英寸IGBT先进工艺技术、第四代高压双扩散金属氧化物半导体 (DMOS+) IGBT技术和第五代沟槽栅IGBT技术等关键技术问题，实现了高压IGBT芯片制造从6英寸到8英寸的技术突破，自主开发的1600 A/1.7 kV与1500 A/3.3 kV IGBT模块已经被成功制造并通过考核，现已应用于轨道交通牵引系统。

关键词：绝缘栅双极型晶体管 (IGBT) 高功率密度沟槽栅 8英寸轨道交通

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Prohibitin regulates mTOR pathway via interaction with FKBP8

Jiahui Zhang, Yanan Yin, Jiahui Wang, Jingjing Zhang, Hua Liu, Weiwei Feng, Wen Yang, Bruce Zetter, Yingjie Xu

《医学前沿（英文）》 2021年第15卷第3期页码 448-459 doi: 10.1007/s11684-020-0805-6

摘要： The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer. The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells. The PI3K–Akt–mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth. Unsurprisingly, it is also one of the most commonly attempted targets for cancer therapy. FK506 binding protein 8 (FKBP8) is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function. We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a “switch” type regulator. We identified through immunoprecipitation–mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1 (PHB1) specifically interacts with FKBP8. Furthermore, the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway, whereas the FKBP8 level in the mitochondria was substantially reduced. Moreover, concomitant with these changes, the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1. Collectively, our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.

关键词： prohibitin 1 FKBP8 mTOR cell proliferation cancer

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Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic

《医学前沿（英文）》 2022年第16卷第6期页码 909-918 doi: 10.1007/s11684-021-0890-1

摘要： In patients with acute promyelocytic leukemia (APL), intracranial hemorrhage (ICH), if not identified promptly, could be fatal. It is the leading cause of failure of induction and early death. Thus, biomarkers that could promptly predict severe complications are critical. Here, cytokine differences between patients with APL with and without ICH were investigated to develop predictive models for this complication. The initial cytokine profiling using plasma samples from 39 patients and 18 healthy donors found a series of cytokines that were remarkedly different between patients with APL and healthy controls. The APL patients were subsequently divided into high and low white blood cell count groups. Results showed that tumor necrosis factor α and interleukin 8 (IL-8) were vital in distinguishing patients with APL who did or did not develop ICH. In addition, verification in 81 patients with APL demonstrated that the two cytokines were positively correlated with the cumulative incidence of ICH. Finally, in-vitro and in-vivo experimental evidence were provided to show that IL-8 influenced the migration of APL-derived NB4 cells and impaired the blood–brain barrier in PML/RARα positive blast-transplanted FVB/NJ mice. These assessments may facilitate the early warning of ICH and reduce future mortality levels in APL.

关键词： acute promyelocytic leukemia intracranial hemorrhage cytokines biomarker

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Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction

Hong LI,Ziding ZHANG

《农业科学与工程前沿（英文）》 2016年第3卷第2期页码 102-112 doi: 10.15302/J-FASE-2016100

摘要： Plants are frequently affected by pathogen infections. To effectively defend against such infections, two major modes of innate immunity have evolved in plants; pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity. Although the molecular components as well as the corresponding pathways involved in these two processes have been identified, many aspects of the molecular mechanisms of the plant immune system remain elusive. Recently, the rapid development of omics techniques (e.g., genomics, proteomics and transcriptomics) has provided a great opportunity to explore plant–pathogen interactions from a systems perspective and studies on protein–protein interactions (PPIs) between plants and pathogens have been carried out and characterized at the network level. In this review, we introduce experimental and computational identification methods of PPIs, popular PPI network analysis approaches, and existing bioinformatics resources/tools related to PPIs. Then, we focus on reviewing the progress in genome-wide PPI networks related to plant–pathogen interactions, including pathogen-centric PPI networks, plant-centric PPI networks and interspecies PPI networks between plants and pathogens. We anticipate genome-wide PPI network analysis will provide a clearer understanding of plant–pathogen interactions and will offer some new opportunities for crop protection and improvement.

关键词： plant–pathogen interactions systems biology omics plant immunity protein–protein interaction network

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IRF4 and IRF8 expression are associated with clinical phenotype and clinico-hematological response to

《医学前沿（英文）》 2022年第16卷第3期页码 403-415 doi: 10.1007/s11684-021-0858-1

摘要： The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P <0.05) and IRF4 (P<0.001) and between white blood cell (WBC) count and IRF4 expression (P <0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P <0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%, 10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.

关键词： myeloproliferative neoplasms IRF4 IRF8 hydroxyurea essential thrombocythemia

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Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology

null

《医学前沿（英文）》 2013年第7卷第1期页码 25-30 doi: 10.1007/s11684-013-0244-8

摘要：

Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family. It actually functions as endocrine hormones but does not regulate cell growth and differentiation. It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism, including enhancing insulin sensitivity, decreasing triglyceride concentrations, causing weight loss, ameliorating obesity-associated hyperglycemia and hyperlipidemia. Moreover, FGF21 also plays important roles in some physiological processes, such as fasting and feeding, growth hormone axis and thermogenic function of brown adipose tissue. Clinical relevance of FGF21 in humans is still unclear, and the basis and consequences of increased FGF21 in metabolic disease remain to be determined. Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease, but some questions remain to be answered. This article concentrates on recent advances in our understanding of FGF21.

关键词： FGF21 metabolism pharmacology physiology clinical relevance

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Parametric study on the mixed solvent synthesis of ZIF-8 nano- and micro-particles for CO adsorption:

Alireza Hadi, Javad Karimi-Sabet, Abolfazl Dastbaz

《化学科学与工程前沿（英文）》 2020年第14卷第4期页码 579-594 doi: 10.1007/s11705-018-1770-3

摘要： The room temperature synthesis of ZIF-8 micro- and nano-particles was investigated using a mixed methanol-water solvent system. ZIF-8 particles of good quality and high crystallinity were obtained. Response surface methodology was used to determine the effect of the synthesis conditions on the ZIF-8 yield, particle size distribution, and mean particle size. The ligand/metal salt molar ratio followed by the amount of sodium formate (the deprotonating agent) and then the amount of water (i.e., the composition of the mixed solvent) respectively had the largest effects on both the ZIF-8 yield and particle size. Results showed that mixing of solvents with different strengths in producing ZIF-8 crystals is a practical method to size-controlled synthesis of ZIF-8 particles. This method is more favorable for industrial-scale ZIF-8 synthesis than using excess amounts of ligands or chemical additives (like sodium formate). In addition, ZIF-8 samples with different mean particle sizes (100, 500, and 1000 nm) were used for CO adsorption and the mid-sized ZIF-8 particles had the highest adsorption capacity.

关键词： metal organic frameworks zeolitic imidazolate frameworks ZIF-8 response surface methodology Box Behnken design CO adsorption