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微滤联合大孔树脂纯化蓝莓果脯糖浆中花色苷的工艺优化

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食品工业科技 2024年第9期45卷 177-185页

作者：朱成成隋世有魏文毅贾建刘伟田伟孟令伟金丽梅李志江黑龙江八一农垦大学食品学院黑龙江大庆163319 黑龙江省农产品加工工程技术研究中心黑龙江大庆163319 黑龙江省杂粮加工及质量安全工程技术研究中心黑龙江大庆163319 国家杂粮工程技术中心黑龙江大庆163319

本文使用微滤技术联合大孔树脂技术对蓝莓果脯糖浆分离纯化,以回收其中的蓝莓花色苷。首先通过静态试验对大孔树脂进行筛选,并在动态试验中以花色苷回收率和总糖去除率为指标,在单因素和Box-Behnken响应面试验的基础上,优化了上样流速... 详细信息

本文使用微滤技术联合大孔树脂技术对蓝莓果脯糖浆分离纯化,以回收其中的蓝莓花色苷。首先通过静态试验对大孔树脂进行筛选,并在动态试验中以花色苷回收率和总糖去除率为指标,在单因素和Box-Behnken响应面试验的基础上,优化了上样流速、乙醇浓度和洗脱流速等工艺参数。结果表明:微滤透过液中花色苷含量为6.84 mg/100 mL,总糖含量为31.76 mg/mL。AB-8、D101、HPD600三种树脂中,优选出AB-8用于蓝莓果脯花色苷的纯化,大孔树脂纯化花色苷最佳工艺条件为:上样流速2.0 mL/min、乙醇浓度83%、洗脱流速2.0 mL/min,该条件下花色苷的回收率为86.68%,总糖去除率为84.13%。花色苷解吸液经旋转蒸发浓缩后,花色苷质量浓度为5.56 mg/100 mL,总糖浓度为5.24 mg/mL,花色苷的色价为31.43,约为原料中花色苷色价的5倍。微滤联合大孔树脂纯化蓝莓果脯糖浆花色苷效果明显,本研究为蓝莓花色苷的分离纯化提供了一定的技术参考。

关键词：蓝莓果脯糖浆花色苷微滤大孔树脂纯化

Phosphorylation of Rictor at Thr1135 impairs the Rictor/Cullin-1 complex to ubiquitinate SGK1

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Protein & Cell 2010年第10期1卷 881-885页

作者： Daming Gao Lixin Wan wenyi wei Department of Pathology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA

The Rictor/mTOR complex plays a pivotal role in a variety of cellular functions including cellular metabolism,cell proliferation and survival by phosphorylating Akt at Ser473 to fully activate the Akt ***,its upstream regulatory pathways as well as whether it has additional function(s)remain largely *** recently reported that Rictor contains a novel ubiquitin E3 ligase activity by forming a novel complex with Cullin-1,but not with other Cullin family ***,we identified SGK1 as its downstream ***,Rictor,but not Raptor or mTOR,promotes SGK1 *** a result,SGK1 expression is elevated in Rictor^(–/–)*** further defined that as a feedback mechanism,Rictor can be phosphorylated by multiple AGC family kinases including Akt,S6K and *** of Rictor at the Thr1135 site did not affect its kinase activity towards phosphorylating its conventional substrates including Akt and *** the other hand,it disrupted the interaction between Rictor and ***,T1135E Rictor was defective in promoting SGK1 ubiquitination and *** finding further expands our knowledge of Rictor’s ***,our work also illustrates that Rictor E3 ligase activity could be governed by specific signaling kinase cascades,and that misregulation of this process might contribute to SGK overexpression which is frequently observed in various types of cancers.

关键词： mTORC2 Rictor kinase E3 ubiqutin ligase Cullin-1 SGK1

Role of SKP1-CUL1-F-Box-Protein (SCF) E3 Ubiquitin Ligases in Skin Cancer

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Journal of Genetics and Genomics 2013年第3期40卷 97-106页

作者： Chuan-Ming Xie wenyi wei Yi Sun School of Biomedical Sciences The Chinese University of Hong Kong Shatin New Territories Department of Pathology Beth Israel Deaconess Medical Center Harvard Medical School Division of Radiation and Cancer Biology Department of Radiation Oncology University of Michigan

Many biological processes such as cell proliferation, differentiation, and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins. While protein synthesis can be regulated at multiple levels, protein degradation is mainly controlled by the ubiquitin-proteasome system （UPS）, which consists of two distinct steps：（1） ubiquitylation of targeted protein by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase, and （2） subsequent degradation by the 26S proteasome. Among all E3 ubiquitin ligases, the SCF （SKP1-CUL1-F-box protein） E3 ligases are the largest family and are responsible for the turnover of many key regulatory proteins. Aberrant regulation of SCF E3 ligases is associated with various human diseases, such as cancers, including skin cancer. In this review, we provide a comprehensive overview of all currently published data to define a promoting role of SCF E3 ligases in the development of skin cancer. The future directions in this area of research are also discussed with an ultimate goal to develop small molecule inhibitors of SCF E3 ligases as a novel approach for the treatment of human skin cancer. Furthermore, altered components or substrates of SCF E3 ligases may also be developed as the biomarkers for early diagnosis or predicting prognosis.

关键词： Carcinogenesis F-box proteins RING proteins SCF E3 ligases Skin Ubiquitin ligases

Dual phosphorylation of Sin1 at T86 and T398 negatively regulates mTORC2 complex integrity and activity

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Protein & Cell 2014年第3期5卷 171-177页

作者： Pengda Liu Jianping Guo Wenjian Gan wenyi wei Department of Pathology Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02115 USA

Mammalian target of rapamycin （mTOR） plays essen- tial roles in cell proliferation, survival and metabolism by forming at least two functional distinct multi-protein complexes, mTORC1 and mTORC2. External growth signals can be received and interpreted by mTORC2 and further transduced to mTORCI. On the other hand, mTORC1 can sense inner-cellular physiological cues such as amino acids and energy states and can indi- rectly suppress mTORC2 activity in part through phosphorylation of its upstream adaptors, IRS-1 or Grbl0, under insulin or IGF-1 stimulation conditions. To date, upstream signaling pathways governing mTORC1 activation have been studied extensively, while the mechanisms modulating mTORC2 activity remain largely elusive. We recently reported that Sin1, an essential mTORC2 subunit, was phosphorylated by either Akt or S6K in a cellular context-dependent manner. More importantly, phosphorylation of Sin1 at T86 and T398 led to a dissociation of Sin1 from the functional mTORC2 holo-enzyme, resulting in reduced Akt activity and sensitizing cells to various apoptotic challenges. Notably, an ovarian cancer patient-derived Sin1-R81T mutation abolished Sin1-T86 phosphoryla- tion by disrupting the canonical S6K-phoshorylation motif, thereby bypassing Sinl-phosphorylation-medi- ated suppression of mTORC2 and leading to sustained Akt signaling to promote tumorigenesis. Our work therefore provided physiological and pathological evi- dence to reveal the biological significance of Sin1 phosphorylation-mediated suppression of the mTOR/ Akt oncogenic signaling, and further suggested that misregulation of this process might contribute to Akt hyper-activation that is frequently observed in human cancers.

关键词： mTORC1 AND mTORC2 ARE FUNCTIONALLYDISTINCT mTOR-CONTAINING PROTEIN KINASECOMPLEXES

基于文献计量的蔓越莓食品研究现状和热点分析

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食品工业科技 2024年第19期45卷 94-103页

作者：赵晨雨朱丹朱立斌杨天佑牛广财魏文毅张玙璠黑龙江八一农垦大学食品学院黑龙江大庆163319 黑龙江省农产品加工工程技术研究中心黑龙江大庆163319 黑龙江八一农垦大学生命科学技术学院黑龙江大庆163319

本文基于文献计量学方法,检索了2013~2023年CNKI总库中收录的蔓越莓食品领域相关研究文献,并进行下一步分析。通过筛选得到中英文文献共计444篇,使用CiteSpace软件从年度发文量、发文期刊、国家、作者及其机构以及关键词共现、聚类、突... 详细信息

本文基于文献计量学方法,检索了2013~2023年CNKI总库中收录的蔓越莓食品领域相关研究文献,并进行下一步分析。通过筛选得到中英文文献共计444篇,使用CiteSpace软件从年度发文量、发文期刊、国家、作者及其机构以及关键词共现、聚类、突现词等角度分析该领域的研究现状和热点。结果显示:2013~2023年发文量总体呈稳定趋势,平均年度发文量约为40篇。发文量最高的期刊是Food Chemistry(25篇),约占文献总数的6%,其次是Food&Function(22篇)和Journal of Agricultural and Food Chemistry(20篇)。美国、波兰、加拿大的发文量在发文国家中排行前3。发文最多的作者是来自美国Ocean Spray公司的研究人员Christina Khoo(17篇)。从CNKI数据库中关键词分析可以看出,出现频率最高的关键词分别是蔓越莓、原花青素、蔓越莓果汁、生物活性成分、尿路感染、抗氧化性能、肠道微生物群和加工工艺、保健功能等,蔓越莓食品领域文献研究热点多集中在蔓越莓成分及功能研究和探讨蔓越莓果汁等新型加工制品在食品行业中的应用等方面。本文对CNKI数据库中文献进行了的综合分析,可为我国蔓越莓食品行业科研人员从事相关研究指明方向,对预测行业未来发展趋势提供数据参考和帮助。

关键词：蔓越莓食品文献计量分析研究热点 CiteSpace

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DUB-independent regulation of pVHL by OTUD6B suppresses hepatocellular carcinoma

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Protein & Cell 2020年第8期11卷 546-548页

作者： Xiaoming Dai Jing Liu wenyi wei Department of Pathology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02115USA

Oxygen is vital for most living *** the course of evolution, animals have developed a highly conserved and elegant pathway to regulate oxygen sensing that converges on the heterodimeric transcription factor called hypoxia-inducible factor (HIF), which contains HIF-1o, a labile alpha subunit and HIF-1β, a stable beta subunit (Wang et al., 1995;Kaelin & Ratcliffe, 2008).In the presence of oxygen, HIF-1α is hydroxylated on the proline-402 and proline-564 residues by the family of Egg-Laying Defective Nine dioxygenases (EglN),which are also called Prolyl Hydroxylase Domain (PHD) proteins (Bruick & McKnight, 2001;Epstein et al., 2001;Ivan et al., 2002).The proline hydroxylation post-translational modification subsequently recruits the Cullin 2VHL E3 ubiquitin ligase complex which comprises the von Hippel-Lindau tumor suppressor (pVHL), Elongin B, Elongin C, Rbx1 and Cullin 2 (Zhang et al., 2019).Specific recognition of the proline-hydroxylation modification by Cullin 2VHL leads to the ubiquitination and subsequent proteasomal degradation of HIF-1α.As such, under low oxygen conditions, deficit in the proline hydroxylation of HIF-1α would lead to its stabilization and activation, thus promoting the transcription of hundreds of target genes, such as vascular endothelial growth factor and erythropoietin (Zhang et al., 2019).These H IF-1α target genes normally serve to promote acute or chronic adaptation to hypoxia, facilitate angiogenesis and thus favor the growth of solid tumor (Wilson & Hay, 2011).

关键词： hundreds stabilization subsequent

Functional analysis of the emerging roles for the KISS1/KISS1R signaling pathway in cancer metastasis

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Journal of Genetics and Genomics 2022年第3期49卷 181-184页

作者： Zhenxi Li Jing Liu Hiroyuki Inuzuka wenyi wei Department of Pathology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02115USA

Cancer metastasis, a process that primary tumor cells disseminate to secondary organs, is the most lethal and least effectively treated characteristic of human cancers. Kisspeptins are proteins encoded by the KISS1 gene that was originally described as a melanoma metastasis suppressor gene. Then, Kisspeptins were discovered as the natural ligands of the G-protein-coupled receptor 54(GPR54) that is also called KISS1R. The KISS1/KISS1R signaling is essential to control Gn RH secretion during puberty and to establish mammalian reproductive function through the hypothalamic-pituitary-gonadal(HPG) axis. Although KISS1primarily plays a suppressive role in the metastasis progression in several cancer types, emerging evidence indicates that the physiological effect of KISS1/KISS1R in cancer metastasis is tissue context-dependent and still controversial. Here, we will discuss the epigenetic mechanism involved in the regulation of KISS1 gene expression, the context-dependent role of KISS1/KISS1R, prometastasis/anti-metastasis signaling pathways of KISS1/KISS1R, and the perspective anticancer therapeutics via targeting KISS1/KISS1R.

关键词： KISS1/KISS1R Metastasis Anticancer therapeutics

The role of ubiquitination in tumorigenesis and targeted drug discovery

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2294-2321页

作者： Lu Deng Tong Meng Lei Chen wenyi wei Ping Wang College of Animal Science and Technology Northwest A&F UniversityYangling Shaanxi 712100China Division of Spine Department of OrthopedicsTongji Hospital Affiliated to Tongji University School of Medicine389 Xincun RoadShanghaiChina Division of Laboratory Safety and Services Northwest A&F UniversityYangling Shaanxi 712100China Department of Pathology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA Tongji University Cancer Center Shanghai Tenth People’s Hospital of Tongji UniversitySchool of MedicineTongji UniversityShanghai 200092China

Ubiquitination,an important type of protein posttranslational modification(PTM),plays a crucial role in controlling substrate degradation and subsequently mediates the“quantity”and“quality”of various proteins,serving to ensure cell homeostasis and guarantee life *** regulation of ubiquitination is multifaceted and works not only at the transcriptional and posttranslational levels(phosphorylation,acetylation,methylation,etc.)but also at the protein level(activators or repressors).When regulatory mechanisms are aberrant,the altered biological processes may subsequently induce serious human diseases,especially various types of *** tumorigenesis,the altered biological processes involve tumor metabolism,the immunological tumor microenvironment(TME),cancer stem cell(CSC)stemness and so *** regard to tumor metabolism,the ubiquitination of some key proteins such as RagA,mTOR,PTEN,AKT,c-Myc and P53 significantly regulates the activity of the mTORC1,AMPK and PTEN-AKT signaling *** addition,ubiquitination in the TLR,RLR and STING-dependent signaling pathways also modulates the ***,the ubiquitination of core stem cell regulator triplets(Nanog,Oct4 and Sox2)and members of the Wnt and Hippo-YAP signaling pathways participates in the maintenance of CSC *** on the altered components,including the proteasome,E3 ligases,E1,E2 and deubiquitinases(DUBs),many molecular targeted drugs have been developed to combat *** them,small molecule inhibitors targeting the proteasome,such as bortezomib,carfilzomib,oprozomib and ixazomib,have achieved tangible *** addition,MLN7243 and MLN4924(targeting the E1 enzyme),Leucettamol A and CC0651(targeting the E2 enzyme),nutlin and MI‐219(targeting the E3 enzyme),and compounds G5 and F6(targeting DUB activity)have also shown potential in preclinical cancer *** this review,we summarize the latest progress in understanding the substrates for ubiquitination and their special functions

关键词： metabolism ubiquitin targeted

PCAF and SIRT1 modulateβTrCP1 protein stability in an acetylation-dependent manner

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Journal of Genetics and Genomics 2021年第7期48卷 652-655页

作者： Fabin Dang Cong Jiang Tao Zhang Hiroyuki Inuzuka wenyi wei Department of Pathology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA

Ubiquitination plays critical roles in regulating various physiological events,such as protein degradation,activation,secretion,sorting and trafficking(Dang et al.,2021).The ubiquitination process involves three major steps,catalyzed by ubiquitin-activating enzymes(E1s),ubiquitin-conjugating enzymes(E2s),and ubiquitin ligases(E3s),respectively(Scheffner et al.,1995).

关键词： stability steps catalyzed