更新于：2024-11-01

NKRF

更新于：2024-11-01

基本信息

别名

ITBA4、NF-kappa-B-repressing factor、NF-kappaB repressing factor

+ [6]

简介

Enhances the ATPase activity of DHX15 by acting like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity of DHX15 (PubMed:12381793). Involved in the constitutive silencing of the interferon beta promoter, independently of the virus-induced signals, and in the inhibition of the basal and cytokine-induced iNOS promoter activity (PubMed:12381793). Also involved in the regulation of IL-8 transcription (PubMed:12381793). May also act as a DNA-binding transcription regulator: interacts with a specific negative regulatory element (NRE) 5'-AATTCCTCTGA-3' to mediate transcriptional repression of certain NK-kappa-B responsive genes (PubMed:10562553).

关联

项与 NKRF 相关的药物

Uroacitides

尿多酸肽

靶点

NKRF

作用机制

核因子κB抑制因子抑制剂

在研机构

合肥永生制药有限公司

原研机构

合肥立方制药股份有限公司

在研适应症

乳腺癌 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2004-07-23

Triolex

靶点

ERK x NKRF

作用机制

ERK抑制剂 [+1]

在研机构

NeurMedix, Inc. [+1]

原研机构

Harbor Diversified, Inc. [+1]

在研适应症

阿尔茨海默症 [+6]

非在研适应症

肌萎缩侧索硬化 [+18]

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

Akt gene inhibitors(University of North Carolina)

靶点

Akt x NKRF

作用机制

AKT基因抑制剂 [+1]

在研机构

National Taiwan University Innovation & Incubation Co. Ltd. [+2]

原研机构-

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 NKRF 相关的临床试验

NCT05970575 / Recruiting临床2期IIT

Open Label Phase IIa Study Evaluating the Safety and Efficacy of NE3107 in Improving Sleep and Fatigue in Subjects With Traumatic Brain Injury

This study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Traumatic Brain Injury and inflammatory and metabolic parameters.

开始日期2023-12-21

申办/合作机构

BioVie, Inc.

NCT05227820 / Completed临床2期IIT

Anti-Inflammatory, Insulin-Sensitizing Agent for Treatment of Cognitive Decline Due to Degenerative Dementias

This study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Alzheimer's disease and inflammatory and metabolic parameters that can be measure in the central nervous system (CNS) with advanced neuroimaging techniques in patients treated with NE3107 (17a-ethynyl-androst-5-3b,7b,17b-triol).

开始日期2022-01-19

申办/合作机构

BioVie, Inc.

NCT05083260 / Completed临床1/2期

A Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetics Study in Parkinson's Disease (PD) Participants Treated With Carbidopa/Levodopa and NE3107

A 28-day phase 2a, double-blind, placebo-controlled (1:1), multi-center study of 20 mg NE3107, twice daily of safety, potential drug-drug interactions, and MDS-UPDRS defined activity in patients with Parkinson's disease . Study will enroll 40 patients that are currently taking immediate release levodopa/ carbidopa (IRLC) and have a practically defined early morning off-state for IRLC. Day one- baseline UPDRS and IRLC PK sampling; day 2- start NE3107 dosing, assess UPDRS during onset and NE3107 PK sampling, rescue meds as needed after 4 hours; day 3 and 14- NE3107 + IRLC UPDRS assessment and PK sampling; day 28- NE3107 + IRLC UPDRS assessments. Optional overnight stays in clinic prior to Day 1-3, 14, and 28.

开始日期2022-01-04

申办/合作机构

BioVie, Inc.

100 项与 NKRF 相关的临床结果

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100 项与 NKRF 相关的转化医学

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0 项与 NKRF 相关的专利（医药）

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537

项与 NKRF 相关的文献（医药）

2025-01-01·Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

Time-restricted feeding modulates gene expression related with rhythm and inflammation in Mongolian gerbils

Article

作者: Wang, Xi-Zhi ; Wang, Zhen-Shan ; Zhang, Xue-Ying ; Wang, Chen-Zhu ; Yang, Lin ; Wang, De-Hua

Time-restricted feeding (TRF) has the potential to modulate circadian rhythm and widely studied in humans and laboratory mice. However, less is known about the physiological responses to TRF in wild mammals. Here, we used Mongolian gerbils, Meriones unguiculatus, to explore the effect of 6-week TRF on gene expression related with circadian rhythm and inflammation. The TRF gerbils had higher cumulative food intake than the ad libitum (AL) group, but body mass, feeding frequency/time and metabolic rate did not differ between groups. In the hypothalamus, downregulation of rhythm-related genes Per3, Cry1 and Dbp was detected in the daytime-restricted feeding (DRF) group and Cry1 was downregulated in the nighttime-restricted feeding (NRF) group. In the liver, the expression of Per1/3, Rev-erbα/β and Dbp was lower, and Bmal1 was higher in the DRF than in AL group, while NRF gerbils showed no changes. In the colon, the expression of Bmal1 and Cry1 was higher but Per3, Rev-erbα/β and Dbp were lower in the DRF than in AL group. Further, the expression of inflammation-related genes such as NF-κB, IL-1β, IL-18 and Nlrp3 was lower in the liver of DRF gerbils, and IL-1β was lower both in the hypothalamus and liver of NRF gerbils. Moreover, the genes related with inflammation such as NF-κB, Nlrp3, IL-10/18/1β and Tnf-α were positively or negatively correlated with multiple rhythm-related genes in the central and peripheral organs. In conclusion, TRF, particularly DRF, could modulate rhythm-related genes in the central and peripheral tissues and reduce hepatic expression of inflammation-related genes in gerbils.

2024-12-31·Epigenetics

TET1 inhibits the migration and invasion of cervical cancer cells by regulating autophagy

Article

作者: Ren, Ji ; Ding, Yan ; Tan, Yujie ; Zan, Yuxin ; Chen, Xiuying ; Wang, Shan ; Li, Jing

Methylation modifications play pertinent roles in regulating gene expression and various biological processes. The silencing of the demethylase enzyme TET1 can affect the expressions of key oncogenes or tumour suppressor genes, thus contributing to tumour formation. Nonetheless, how TET1 affects the progression of cervical cancer is yet to be elucidated. In this study, we found that the expression of TET1 was significantly downregulated in cervical cancer tissues. Functionally, TET1 knockdown in cervical cancer cells can promote cell proliferation, migration, invasion, cervical xenograft tumour formation and EMT. On the contrary, its overexpression can reverse the aforementioned processes. Moreover, the autophagy level of cervical cancer cells can be enhanced after TET1 knockdown. Mechanistically, methylated DNA immunoprecipitation (MeDIP)-sequencing and MeDIP quantitative real-time PCR revealed that TET1 mediates the methylation of autophagy promoter regions. These findings suggest that TET1 affects the autophagy of cervical cancer cells by altering the methylation levels of NKRF or HIST1H2AK, but the specific mechanism needs to be investigated further.

2024-12-01·International Journal of Pharmaceutics

Zein nanoparticles extend lifespan in C. elegans and SAMP8 mice

Article

作者: Reboredo, Cristian ; Vizmanos, José L. ; González-Navarro, Carlos J. ; Vizmanos, José L ; Solas, Maite ; González-Navarro, Carlos J ; Martínez-López, Ana L. ; Irache, Juan M. ; Irache, Juan M ; Javier Ramírez, María ; Puerta, Elena ; Martínez-López, Ana L

Empty zein nanoparticles (NP) have been shown to lower glycemia in rats by stimulating the secretion of endogenous GLP-1. This study evaluated the effect of these nanoparticles on the lifespan of two animal models: C. elegans fed with a glucose-rich diet and the senescence accelerated mouse-prone 8 (SAMP8 mice). In C. elegans, NP increased the mean lifespan of worms by 7 days (from 17.1 for control to 24.5 days). This observation was in line with the observed significant reductions of glucose and fat contents, lipofuscin accumulation, and ROS expression. Furthermore, NP supplementation led to an upregulation of the expression of daf-16 and skn-1 genes. DAF-16 (orthologue of the FOXO family) and SKN-1 (orthologue of mammalian Nrf/CNC proteins) are implicated in activating detoxification mechanisms against oxidative damage. In SAMP8, oral administration of NP also extended the mean lifespan of mice (by 28 % compared to controls), corroborating the protective effect of these nanoparticles.

项与 NKRF 相关的新闻（医药）

2023-09-09

·生物制品圈

山大齐鲁研究发现病理性心脏重塑治疗靶点

导读：心肌梗塞（MI）仍然是全球死亡的主要原因。心脏成纤维细胞（CF）在心脏中含量丰富，负责心肌梗死后的心脏修复。NF-κB抑制因子（NKRF）在各种特定基因的转录抑制中起重要作用。然而，在心肌梗死后心脏修复中，CFs的NKRF作用机制仍不清楚。近日，山东大学齐鲁医院张澄、张猛和孔静共同通讯在《Advanced Science》上发表题为“NKRF in Cardiac Fibroblasts Protects against Cardiac Remodeling Post-Myocardial Infarction via Human Antigen R”的研究论文，通过建立CF特异性NKRF敲除（NKRF-CKO）小鼠模型，研究NKRF在心肌梗死后心脏重塑和功能障碍中的机制。https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/full/10.1002/advs.202303283研究背景 01 心脏重塑是几乎所有导致心功能不全和心力衰竭发病率和死亡率增加的心血管疾病的共同病理结果。心肌梗塞（MI）引起的缺血性心脏病和心力衰竭仍然是全世界死亡的主要原因。心肌梗死后瘢痕形成在预防早期心室破裂和晚期泵血功能方面起着重要作用。细胞外基质（ECM）作为机械支架，在生理条件下传递信号，并在病理条件下参与瘢痕形成、心脏重塑和心脏功能维持。ECM稳态通过胶原蛋白分泌与基质金属蛋白酶（MMP）和MMP组织抑制剂（TIMP）的活化之间的平衡变化来维持。心脏成纤维细胞（CFs）是所有心脏细胞类型中最丰富的，在调节ECM中起着重要作用。心肌梗死后的心脏修复是一系列精心策划的复杂事件，大致可分为早期炎症/坏死阶段和晚期纤维化/增殖阶段。许多炎症细胞（包括中性粒细胞和巨噬细胞）在早期炎症/坏死期释放许多炎症因子，并激活和分泌MMP以消化和清除受损细胞和ECM组织。释放的MMP通过破坏ECM中的胶原纤维和支柱来影响ECM的稳态。许多CF迁移到梗死区，分化成肌成纤维细胞，并在纤维化/增殖后期分泌大量原胶原以促进瘢痕形成和梗死修复。在炎症/坏死早期适当和及时地限制炎症程度和持续时间是纤维化/增殖后期伤口愈合质量的决定因素。以前的大多数研究仅关注早期炎症/坏死阶段的巨噬细胞和心肌细胞（CMs）或CFs对晚期纤维化/增殖期MI后心脏重塑的影响。需要更多的研究来了解炎症如何影响心肌梗死后的心脏功能，方法是探索CF衍生ECM重塑的分子决定因素。研究进展 02 Transwell侵袭系统的聚碳酸酯膜的上部隔室涂有一层基质胶，以模拟体外的ECM。这种 ECM 模拟需要CF 分泌MMP以降解ECM并促进它们迁移到下隔室（图 3A）。TNF-α显著增加了CF对下隔室的侵袭，但NKRF过表达抑制了这种作用（图3B）。同样，伤口愈合测定显示，TNF-α随着时间的推移显著增强了CF迁移，并且NKRF过表达抑制了这种增加（图3C）。NKRF通过下调MMP2和MMP9表达来抑制CF迁移和侵袭增加的MMP2和MMP9表达促进CF迁移增加。体内MMP9和MMP2的灭活可预防小鼠心肌梗死后心脏破裂，缓解胶原蛋白积累、左心室扩张和心功能不全。实时聚合酶链反应（RT-PCR）显示，TNF-α诱导后NKRF mRNA水平显著降低（图3D）。TNF-α诱导后MMP2和MMP9的mRNA水平显著升高，NKRF过表达显著抑制了这种作用（图3E，F）。蛋白质水平的变化与mRNA水平的变化一致（图3G）。明胶凝胶内酶谱显示TNF-α显著增加了MMP2和MMP9的活性，但NKRF显著抑制了这种增加（图3H）。此外，构建了NKRF的8个小干扰RNA（siRNA）用于反向敲低验证;第三个siRNA在CFs中表现出最高的敲低效率。敲低实验中TNF-α诱导的NKRF mRNA水平的降低与过表达测定中观察到的一致。在mRNA水平的NKRF敲低后，TNF-α诱导的MMP9和MMP8水平升高进一步增强（。蛋白质水平的变化与mRNA水平的变化一致。NKRF敲低显著放大了TNF-α诱导的MMP9和MMP8活性的增加。综上所述，NKRF过表达通过下调MMP9和MMP<>表达和活性来抑制CF的迁移和侵袭。这表明NKRF在病理性心脏重塑背景下调节ECM重塑和CF行为的潜在作用。研究影响 03 NKRF可作为CF的转录沉默剂，并防止心肌梗死后的心脏重塑。在机制上，NKRF通过以NF-κB依赖性方式与HuR启动子内的NRE结合来抑制HuR的转录，从而抑制Mmp2和Mmp9 mRNA的稳定性。我们的研究结果表明，心肌梗死后患者的早期NKRF靶向是防止晚期心脏重塑的有效策略。这些发现为心肌梗死后心脏重塑的治疗提供了新的见解。参考资料：https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/full/10.1002/advs.202303283识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

临床研究