This randomized clinical trial and laboratory study was conducted to:
Compare the effectiveness of zinc-carbonated nano-hydroxyapatite, arginine, and fluoride-containing toothpastes for treating white spot lesions associated with orthodontically treated teeth by using:
Computerized image software analysis.
Energy dispersive X-ray analysis.

开始日期2023-11-30

申办/合作机构

Mansoura University

NCT06135792

/ CompletedN/AIIT

The Effect of Arginine on Biofilm Composition, Architecture and Metabolism in Caries-active Patients: a Split-mouth in Situ Trial

Arginine is an adjunct to oral health care that has the potential to modulate the composition and activity of the microbial community of dental biofilms towards a health-related status without harmful effects for the resident oral microbiota. The aim of the study is to investigate the effects of arginine treatment compared to placebo on the composition, metabolism, and microarchitecture of biofilms grown in situ in the oral cavity of caries-active participants.

开始日期2023-10-19

申办/合作机构

University of Aarhus

NCT02440061

/ Withdrawn临床1期IIT

Ghrelin Effect on Beta Cell Function in Health and Disease #2

Ghrelin is a hormone naturally produced in the stomach and the gut. The purpose of this research study is to determine the role of this gut hormone in the regulation of insulin secretion from the pancreas and glucose disposal after we eat. The investigators hypothesize that ghrelin has an effect on the pancreas and on how our body handles glucose after we eat. The investigators will compare insulin secretion and glucose changes during meal ingestion while either acyl ghrelin (AG) or saline (salt solution) is being infused through your vein on separate study days. AG is a form of the ghrelin hormone that has a small modification to it that allows it to bind to a specific receptor. The investigators hypothesize that AG has an effect on how the body handles glucose after a meal. AG has been approved by the U.S. Food and Drug Administration (FDA) for human research only. This study will also involve the use of a medicine called arginine, which is a naturally occurring product and found in many nutritional supplements. Its use in this study is investigational. The use of arginine helps maximize insulin release from the pancreas so the investigators can better examine whether AG affects insulin secretion.

开始日期2018-05-01

申办/合作机构

Duke University

[+1]

100 项与 L-Arginine/L-Aspartate 相关的临床结果

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100 项与 L-Arginine/L-Aspartate 相关的转化医学

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100 项与 L-Arginine/L-Aspartate 相关的专利（医药）

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项与 L-Arginine/L-Aspartate 相关的文献（医药）

2024-08-01·Journal of Pharmaceutical Sciences

Designing Robust Monoclonal Antibody Drug Products: Pitfalls of Simplistic Approaches for Stability Prediction

Article

作者: Gokarn, Yatin R ; Saluja, Atul ; Rembert, Kelvin B

Thermal stability attributes including unfolding onset (T_onset) and mid-point (T_m) are often utilized for efficient development of monoclonal antibody (mAb) products during lead selection and formulation screening workflows. An assumption of direct correlation between thermal and kinetic physical stability underpins this basic approach. While literature reports have substantiated this general approach under specific conditions, clear exceptions have been highlighted alongside. Herein, a set of mAbs formulated under diverse solution conditions to generate a broad array of thermal and kinetic stability profiles were systematically analyzed. Sequence modifications in the Fc region were purposefully engineered to generate a set of low-melting mAbs. A diverse set of excipients were subsequently utilized and shown to modulate the T_m over a wide range. While a general correlation between high T_m and low aggregation rate was observed under accelerated conditions, the predictive utility of T_m under relevant product storage conditions was inadequate at best. Critically, T_m data did not correlate with long-term aggregation rates under refrigerated or room temperature conditions. Even under accelerated conditions, T_m appeared to be a poor predictor of aggregation once it exceeded the solution storage temperature (40°C) by ∼15°C, similar to conditions routinely encountered in the development of canonical mAbs (T_m > 60°C). Pitfalls of simplistic correlative approaches are discussed in the context of practical biologics product development.

2024-08-01·Nature Structural & Molecular Biology

Mechanism of autocatalytic activation during proteasome assembly

Article

作者: Adams, Lea ; Huang, Lan ; Perez, Erignacio Fermin ; Blickling, Marie ; Razi, Aida ; Rajakumar, Tamayanthi ; Jiao, Fenglong ; Fung, Darlene ; Walsh, Richard M ; Rawson, Shaun ; Hanna, John ; Velez, Benjamin

Many large molecular machines are too elaborate to assemble spontaneously and are built through ordered pathways orchestrated by dedicated chaperones. During assembly of the core particle (CP) of the proteasome, where protein degradation occurs, its six active sites are simultaneously activated via cleavage of N-terminal propeptides. Such activation is autocatalytic and coupled to fusion of two half-CP intermediates, which protects cells by preventing activation until enclosure of the active sites within the CP interior. Here we uncover key mechanistic aspects of autocatalytic activation, which proceeds through alignment of the β5 and β2 catalytic triad residues, respectively, with these triads being misaligned before fusion. This mechanism contrasts with most other zymogens, in which catalytic centers are preformed. Our data also clarify the mechanism by which individual subunits can be added in a precise, temporally ordered manner. This work informs two decades-old mysteries in the proteasome field, with broader implications for protease biology and multisubunit complex assembly.

2023-10-01·Heliyon

Prophylaxis of decidual CD68+/CD163+ macrophage disbalance in extracorporeal fertilized women

Article

作者: Akimov, Oleh ; Taranovska, Olena ; Likhachov, Volodymyr ; Shimanska, Yanina ; Kaidashev, Igor ; Zhabchenko, Iryna ; Vashchenko, Viktoriya

The demographic crisis that prevailed in Ukraine in recent years, the state of war as a result of the aggression of the Russian Federation, reproductive losses among women of childbearing age are one of the most urgent problems in modern obstetrics and gynecology. One of the most effective methods of correcting impaired reproductive function is in vitro fertilization.The purpose of this workis to develop a pharmacological complex for the prevention of imbalance of CD68⁺/CD163⁺ decidual macrophages in vitro fertilized women.Materials and methods105 pregnant women who were divided into 3 groups took part in the study. The first group included 20 women whose pregnancy occurred and is proceeding physiologically. The second group consisted of 85 women who became pregnant as a result of in vitro fertilization, including 37 pregnant women who refused prophylactic correction of the threat of premature birth, and 48 pregnant women who received prophylactic correction of the threat of premature birth: complex prescription of vitamin D3 2000 IU orally 2 times a day, micronized progesterone 200 mg 2 times a day and l-arginine aspartate 1000 mg 4 times a day, starting from 18 to 20 weeks of pregnancy.ResultsIn women who refused prophylactic correction of the threat of premature birth, a local increase in the activity of inducible NO-synthase and concentration of tumor necrosis factor-α, and a decrease in the activity of arginase and in the level of interleukin-10 were observed in the cervical mucus. They have a lower expression of CD163⁺ on placental decidual macrophages and an increased expression of CD68⁺, which indicates a shift in the polarization of macrophages from an anti-inflammatory to a pro-inflammatory phenotype. The use of prophylactic treatment brings the studied parameters closer to the results of women in whom pregnancy occurred physiologically.ConclusionsIn women who became pregnant as a result of in vitro fertilization, at 28-30 weeks of pregnancy, changes specific for pro-inflammatory phenotype of decidual macrophages were observed. Complex administration of vitamin D3, micronized progesterone and l-arginine aspartate lead to restoration of anti-inflammatory phenotype of decidual macrophages.

项与 L-Arginine/L-Aspartate 相关的新闻（医药）

2025-04-18

·药学进展

学科前沿 | 沈阳药科大学在糖尿病慢性伤口愈合研究领域取得新进展

“点击蓝字关注我们沈阳药科大学在糖尿病慢性伤口愈合研究领域取得新进展 PPS 近期，沈阳药科大学药学院袁悦教授课题组在国际权威期刊Carbohydrate Polymers（中科院1区，IF=10.7）发表了题为“Glucose-activated self-cascade antibacterial and pro-angiogenesis nanozyme-functionalized chitosan-arginine thermosensitive hydrogel for chronic diabetic wounds healing”的研究成果，为糖尿病慢性伤口愈合提供了新策略。在皮肤伤口的止血、炎症、增殖和重塑四个连续且协调的过程中，任何异常情况的发生都可能导致伤口难愈合，例如急性出血、感染、烧伤、过度炎症及慢性伤口等。糖尿病患者受持续性高血糖及其引发的糖尿病性神经、血管病变影响，受持续性高血糖和神经血管病变影响，糖尿病伤口易受细菌反复感染并向血管化障碍发展，从而延迟伤口愈合过程。在此背景下，课题组设计了一种局部降血糖、抗菌和促血管新生的双级联纳米酶功能化温敏性水凝胶伤口敷料，以满足糖尿病慢性伤口愈合不同阶段的需求。课题组成功构建了Cu-MOF/GOX-Gel水凝胶，该水凝胶由类Fenton催化剂铜基金属有机框架（Cu-MOF），葡萄糖氧化酶（GOX）、NO供体壳聚糖-精氨酸和波洛萨姆F127组成。GOX通过消耗创面部位的高血糖产生过氧化氢（H2O2）和葡萄糖酸，从而启动高效的抗菌催化级联反应，在伤口愈合的初始阶段有效地预防和控制感染；水凝胶可缓慢释放L-精氨酸（L-Arginine, L-Arg），并在原位生成的H2O2进一步催化下转化为一氧化氮（nitric oxide, NO）逐渐释放，促进伤口处的血管新生和胶原蛋白沉积，加速伤口愈合后续阶段进程。沈阳药科大学药剂学硕士研究生陈书慧为论文第一作者，药学院袁悦教授为通讯作者，沈阳药科大学为唯一通讯单位。该研究得到了沈阳市功能药物载体材料重点实验室项目（NO. 19-110-4-08）和辽宁省教育厅项目（NO. JYTMS20231371）的资助。文章来源：沈阳药科大学美编排版：何裕爽文章审核：孙雯何裕爽罗琪【免责声明】以上内容来源于互联网，不代表本平台立场或观点；如有侵犯作者著作权，请及时与我们联系（Tel：025-83271227，或直接在微信平台留言），我们将及时更正或删除。《药学进展》杂志由国家教育部主管、中国药科大学和中国药学会共同主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

2025-04-13

·ioncology

2025 AACR年会摘要公布，速览泌尿肿瘤领域中国研究及新型药物治疗进展

点击上方蓝字关注我们编者按：2025年美国癌症研究协会（AACR）年会将于当地时间4月25至30日在美国芝加哥举行，本届年会的主题“融合科学与临床——持续创新带来变革（Unifying Cancer Science and Medicine: A Continuum of Innovation for Impact）”，反映了“实验室—临床—实验室”这一癌症研究过程的重要性。在泌尿肿瘤领域，多项中国研究及新型药物治疗入选，这也体现了中国泌尿肿瘤研究的广度和深度。肿瘤瞭望-泌尿时讯特别整理相关研究题目，以飨读者（如有遗漏和错误，欢迎留言指正）。摘要号：742 / 27英文标题：Development and evaluation of a non-invasive qPCR assay for sensitive detection of FGFR2/3 alterations in urine samples as a companion diagnostic for erdafitinib中文标题：开发并评估一种非侵入性qPCR检测方法，用于高灵敏度检测尿液样本中的FGFR2/3变异，作为厄达替尼的伴随诊断讲者：Qing Xu. 中国上海摘要号：LB021 / 21英文标题：TJ102, A promising bispecific dual-payload ADC targeting CDH6 and folate receptor alpha (FRα) for the treatment of ovarian and kidney cancers中文标题：TJ102是一种有前景的双特异性双药ADC，靶向CDH6和叶酸受体α（FRα），用于治疗卵巢癌和肾癌讲者：Shugaku Takeda. 中国上海摘要号：343 / 10英文标题：GenSci143, a novel B7-H3×PSMA bispecific and potential best-in-class ADC, for the treatment of metastatic castration-resistant prostate cancer中文标题：GenSci143，一种新型B7-H3×PSMA双特异性抗体偶联药物，有望成为同类最优ADC药物，用于治疗转移性去势抵抗性前列腺癌讲者：Fu Li 中国上海摘要号：353 / 20英文标题：Preclinical development of MHB048C： A novel anti-PSMA ADC with a potent topoisomerase I inhibitor中文标题：MHB048C的临床前开发：一种具有强效拓扑异构酶I抑制剂的新型PSMA ADC讲者：Guoqing Cao 中国杭州摘要号：576 / 11英文标题：Discovery of FL801, a B7-H3-targeting nanobody-based radioligand vector, using Clear-XTM linker technology中文标题：利用Clear-XTM连接技术发现FL801，一种靶向B7-H3的基于纳米抗体的放射性配体载体讲者：Xiaozhu Wang 中国上海摘要号：446 / 7英文标题：Embryonic ectoderm development protein (EED) inhibitor APG-5918 exhibits potent antitumor activity and synergizes with androgen receptor (AR) inhibitor enzalutamide in preclinical prostate cancer (PCa) models中文标题：胚胎外胚层发育蛋白（EED）抑制剂APG-5918在临床前的前列腺癌（PCa）模型中表现出强大的抗肿瘤活性，并与雄激素受体（AR）抑制剂恩扎卢胺产生协同作用讲者：Yan Yin 中国苏州摘要号：396 / 15英文标题：Discovery of SHR3591, a highly potent and orally bioavailable AR PROTAC for the treatment of prostate cancer中文标题：SHR3591，一种高效且口服生物可利用的AR PROTAC，用于治疗前列腺癌讲者：Minqiang Jia 中国上海摘要号：1015 / 17英文标题：Real-world evaluation of androgen receptor (AR) ligand-binding domain (LBD) mutations in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC)中文标题：对中国转移性去势抵抗性前列腺癌（mCRPC）患者雄激素受体（AR）配体结合域（LBD）突变的真实世界评估讲者：Yufei Chen 中国北京摘要号：1018 / 20英文标题：Genetic landscape and functional exploration of kidney cancer predisposition in cross-ancestral populations中文标题：跨祖先人群肾癌易感性的遗传图谱和功能探索讲者：Hongji Dai 天津医科大学附属肿瘤医院摘要号：1924 / 24英文标题：Urine extracellular vesicles derived CA9 and CIZ1 as non-invasive biomarkers for early diagnosis of clear cell renal cell carcinoma中文标题：尿液细胞外囊泡衍生的CA9和CIZ1作为透明细胞肾细胞癌早期诊断的非侵入性生物标志物讲者：Xiyi Wei 南京医科大学第一附属医院摘要号：1782 / 1英文标题：Preclinical development of iSAP-0909： A novel self-assembled fluorescent contrast agent targeting XIAP for image-guided surgery in bladder cancer中文标题：iSAP-0909临床前开发：一种针对XIAP的新型自组装荧光造影剂，用于膀胱癌图像引导手术讲者：Min Han 中国北京摘要号：1717 / 18英文标题：Establishment and characterization of enzalutamide resistant prostate CDX models中文标题：恩扎卢胺耐药前列腺CDX模型的建立及鉴定讲者：Wen-Jen Yu. 中国北京摘要号：1777 / 29英文标题：OST11098, an orally available and selective Cyp11A1 inhibitor for the treatment of castration-resistant prostate cancer (CRPC) with next-generation hormone agents (NHAs) resistance中文标题：OST11098是一种口服选择性Cyp11A1抑制剂，用于治疗对下一代激素药物（NHA）有抗药性的去势抵抗性前列腺癌（CRPC）讲者：Fangrui Wu. 中国苏州摘要号：1322 / 6英文标题：The DNA methylation signature of the driver gene GPRASP1 serves as an early indicator of progression in prostate cancer中文标题：驱动基因GPRASP1的DNA甲基化特征可作为前列腺癌进展的早期指标讲者：Yi Lu. 南方科技大学摘要号：3672 / 1英文标题：High-sensitivity CRISPR-Cas12a detection of prostate-specific antigen based on computationally optimized aptamers中文标题：基于计算优化配体的前列腺特异性抗原高灵敏度CRISPR-Cas12a检测讲者：Pei Li. 郑州大学基础医学院摘要号：CT111 / 6英文标题：A phase 1, first-in-human study of IB-T101, an OUTLAST™ CAR-T product for the treatment of CD70-positive clear cell renal carcinoma中文标题：IB-T101（OUTLAST™ CAR-T产品）用于治疗CD70阳性透明细胞肾癌的I期首次人体研究讲者：中国上海摘要号：2945 / 19英文标题：PLB-002 is a novel Claudin 6 antibody-drug conjugate for ovarian cancer and testicular germ cell cancer中文标题：PLB-002是一种新型Claudin 6抗体偶联药物，用于治疗卵巢癌和睾丸生殖细胞癌讲者：Haitao Pan 中国苏州摘要号：2869 / 8英文标题：DXC014, a novel bispecific ADC targeting B7-H3 and PSMA, demonstrates favorable antitumor efficacy and safety profiles in preclinical evaluations中文标题：DXC014是一种针对B7-H3和PSMA的新型双特异性ADC，在临床前评估中表现出良好的抗肿瘤疗效和安全性讲者：Huihui Guo 中国杭州摘要号：3495 / 3英文标题：QL535, A novel CD2-costimulating T cell engager targeting PSMA-positive prostate cancer matching CD28 trispecific antibody in cytotoxicity, minimizing cytokine release and T-cell exhaustion中文标题：QL535，一种新型CD2共刺激T细胞衔接剂，靶向PSMA阳性前列腺癌，与CD28三特异性抗体匹配，具有细胞毒性，可最大限度地减少细胞因子释放和T细胞耗竭讲者：Xiao Liu 中国济南摘要号：3439 / 2英文标题：Study on the mechanism of sesamin inhibiting the malignant metastasis of prostate cancer中文标题：芝麻素抑制前列腺癌恶性转移的机制研究讲者：Yen Chen Chen 中国台湾新光吴火狮纪念医院摘要号：LB273 / 22英文标题：HSK46575： A best-in-class, long lasting, small molecular CYP11A1 inhibitor for the treatment of castration-resistant prostate cancer (CRPC)中文标题：HSK46575：同类最佳、长效、小分子CYP11A1抑制剂，用于治疗去势抵抗性前列腺癌（CRPC）讲者：Lulin Huang 中国成都摘要号：4224 / 10英文标题：The pharmacological intervention of protein arginine methyltransferase 1 (PRMT1) leads to metastatic castration-resistant prostate cancer (mCRPC) repression through unique and significant androgen receptor (AR) downregulation and epigenetic modulation中文标题：蛋白质精氨酸甲基转移酶1（PRMT1）的药物干预通过独特且显著的雄激素受体（AR）下调和表观遗传调节导致转移性去势抵抗性前列腺癌（mCRPC）抑制讲者：Hui Shi 中国杭州摘要号：5888 / 13英文标题：Urinary ctDNA tumor fraction monitoring enhances non-invasive assessment of molecular response in bladder-preserving treatment of muscle-invasive bladder cancer中文标题：尿液ctDNA肿瘤分数监测可增强对肌层浸润性膀胱癌保留膀胱治疗中分子反应的无创评估讲者：Haoran Tang 中国上海摘要号：5889 / 14英文标题：Combined cfDNA and cfRNA enhanced gene fusion detection and drug resistance mechanism insights in mCRPC through combined cfDNA and cfRNA assays profiling中文标题：通过联合cfDNA和cfRNA分析，增强mCRPC中的基因融合检测和耐药机制分析讲者：Haoran Tang 中国上海摘要号：5905 / 30英文标题：A non-invasive, methylation-based NGS assay for sensitive detection and monitoring of bladder cancer in urine中文标题：一种基于甲基化的无创NGS检测方法，用于尿液中膀胱癌的灵敏检测和监测讲者：Feng Xie 中国上海摘要号：5123 / 1英文标题：Up-regulation of KRT14 promotes EMT in basal muscle-invasive bladder cancer through IGF2BP1/FTO dependence on methyladenosine-modified SNAI1中文标题：KRT14的上调通过依赖甲基腺苷修饰的SNAI1促进基底肌层浸润性膀胱癌的EMT讲者：Chuanshu Huang. 温州医科大学摘要号：5247 / 7英文标题：Comprehensive characterization of pseudocapsules in clear cell renal cell carcinoma reveals unique invasion mechanisms： A multi-omics investigation中文标题：肾透明细胞癌假包膜的综合表征揭示其独特的侵袭机制：一项多组学研究讲者：Xiyi Wei, 南京医科大学第一附属医院摘要号：6611 / 18英文标题：Genome-wide cfDNA fragmentomics combined with machine learning enhance non-invasive prostate cancer detection中文标题：全基因组cfDNA片段组学与机器学习相结合，增强非侵入性前列腺癌检测讲者：Hang Dong. 中国上海（来源：《肿瘤瞭望-泌尿时讯》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

抗体药物偶联物AACR会议临床结果蛋白降解靶向嵌合体

2025-04-11

·学术经纬

《科学》：清华团队揭示全新染色质重塑机理

▎药明康德内容团队编辑（来源：清华大学）DNA缠绕组蛋白八聚体形成的核小体是染色质的基本单元。染色质重塑蛋白（chromatin remodeler）利用ATP水解的能量移动核小体，从而调节染色质结构与基因表达。染色质重塑蛋白包含4个主要家族：SWI/SNF，ISWI，CHD和INO80，它们具有多种生物学功能。其中，SWI/SNF帮助形成开放的染色质，促进基因表达；而ISWI则感知接头DNA的长度，促进等间距核小体阵列排布，推动紧密染色质结构形成。不同的染色质重塑蛋白具有高度保守的马达结构域（motor domain），是染色质重塑反应的核心。而过度的染色质重塑反应需被抑制，从而避免破坏染色质结构。染色质重塑马达如何克服核小体中组蛋白与DNA的相互作用，滑移核小体的机理并不完全清楚。近日，清华大学生命科学学院陈柱成教授在《科学》杂志在线发表题为“活跃ATP水解过程中ISWI染色质重塑的结构解析” （Structural insights into chromatin remodeling by ISWI during active ATP hydrolysis）的研究论文。过往的结构研究可能由于使用不能被水解的核苷酸底物，只捕捉到三种染色质重塑状态（ATP，ADP和Apo）。这个最新的研究使用ATP维持DNA滑移，让马达蛋白经历重塑循环中所有可能的构象。研究人员设计了不同浓度ATP实验条件，富集不同状态下的构象，并通过冷冻电子显微镜技术，首次从ATP水解过程中解析出ATP、ADP、ADP*、ADP⁺、ADP*⁺、Apo、Apo*、ADPS和ADPB等九种ISWI 结合核小体的动态结构（分辨率2.3-3.0 Å）。这九种结构共同组成了迄今最完整的染色质重塑循环模型，为解释染色质重塑中的DNA滑移和刹车机制奠定了基础。▲图1 存储1 bp DNA隆起的ADP*状态结构（图片来源：原始论文[1]）研究人员发现ISWI马达蛋白在核小体内部（SHL2）引起1 bp DNA隆起（图1）。这个全新构像被命名为ADP*，有别于经典ADP 状态下的1/2 bp DNA形变。ADP*构象中，DNA双链同时从入口端向核小体内部滑移，导致1 bp DNA隆起过渡性地储存在SHL2处，并打破DNA-组蛋白的局部相互作用。这时，ATP水解的化学能变转换成DNA形变的势能。这一现象与两种被广泛关注的染色质重塑机制存在冲突。这既不同于"扭曲传播"（twist diffusion）模型中DNA-组蛋白相互作用保持完整的情况，也有别于"环传播"（loop propagation）模型中多个相邻位点相互作用同时被破坏的特征。ADP*状态的发现找到了染色质重塑循环中缺失的关键拼图，提示一种新的DNA形变传播模式。该工作还发现了ISWI的多个特异调控构象：ADP⁺，ADP*⁺，ADPS以及ADPB。ADP⁺和ADP*⁺具有正向调控元件：RYA（arginine-tyrosine anchor）和PosC（图 2A-C）。ADP⁺和ADP*⁺构象常见于核小体接头DNA较短一侧，可能起到弥补 DNA结合结构域（DBD）锚定不足的作用，从而稳定马达对核小体的结合，促进染色质重塑活性。相反，在ADPB 状态下，正向调控元件作用消失，而新生成的 Brake 元件通过变构作用，导致马达蛋白异常开放，从而落入失活状态（图2D-E）。据此，研究人员提出了染色质重塑的刹车机制，阐明了ISWI 家族特异的接头 DNA 感知机制。▲图2 ISWI调控状态的结构（图片来源：原始论文[1]）研究人员综合所获得的九种构像，提出一个多步骤染色质重塑模型，包括核心的重塑循环和外围的调控状态（图 3）。在核心重塑循环中，ATP 水解释放无机磷酸，马达经历ATP至ADP构像转变，并在 SHL2 位置引发 1/2 bp 的 DNA 形变。马达蛋白进一步倾转，进入ADP* 状态，引发1 bp DNA隆起。随后，ADP*马达蛋白在整体构像不变的情况下释放ADP，进入Apo*状态。新一轮ATP结合促使马达蛋白闭合，马达的定向运动推动DNA链前移，防止DNA逆滑。同时，马达内部结构发生调整，释放与DNA链的紧密接触，使1 bp DNA隆起向出口方向滑移，DNA恢复松弛状态。染色质重塑的分子动画见陈柱成实验室主页连接（www.chenlab.com）。染色质重塑周期中，DNA在ADP 和ADP* 状态下发生形变，使体系处于高能状态，这是调控染色质重塑活性的关键节点。马达在RYA和PosC作用下，可以稳定在APD+ 和ADP*+ 构象，否则容易滑入失去活性的ADPS 和 ADPB 状态。ADPS的结构代表ATP水解的能量未有效转换为DNA形变的状态（打滑状态）。未来需要更多研究分析能量的转换效率。当核小体滑移使得接头DNA变得较短时，DBD失去锚定位点，马达蛋白刹车，进入ADPB状态，从而避免过度的染色质重塑，实现对接头DNA长度的应答。总之，作者认为核心重塑循环是各染色质重塑蛋白中普遍通用的 DNA 滑移机制，而外围调控层则为 ISWI 家族特有。▲图3 染色质重塑DNA滑移和调控模型（图片来源：原始论文[1]）值得一提的是，美国的Mario Halic团队几乎同期解析了人源ISWI（SNF2H）ATP水解过程中的动态结构（预印本，见延伸阅读），证实SHL2储存1 bp DNA隆起的构像在染色质重塑中的普适性。清华大学生命科学学院陈柱成教授为本文通讯作者，清华大学生命科学学院2020级博士生谢悠扬和博士后潘涵为共同第一作者，博士后陈康净也参与了重要工作。本工作获得国家自然科学基金、科技部重大科学研究计划专项、北京生物结构前沿研究中心、清华-北大生命科学联合中心、国家蛋白质科学研究（北京）设施清华基地的大力支持。原始论文：[1] Structural insights into chromatin remodeling by ISWI during active ATP hydrolysis. Science (2025). DOI: 10.1126/science.adu5654免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。更多推荐点个“在看”再走吧~

100 项与 L-Arginine/L-Aspartate 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
炎症	临床3期	乌克兰	Ukrainian Medical Stomatological Academy	2017-10-20
牙周炎	临床3期	乌克兰	Ukrainian Medical Stomatological Academy	2017-10-20

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ESC2018	N/A	代谢综合征	62	L-Arginine aspartate	簾鹽願鹹膚願願糧艱蓋(憲夢網餘鏇鑰顧積選鑰) = 餘遞糧繭醖淵願糧鹽鹽襯膚餘淵糧膚鏇蓋願糧 (鹹夢選選積膚選構衊鹽 ) 更多	-	2018-08-26
				l-arginine aspartate	簾鹽願鹹膚願願糧艱蓋(憲夢網餘鏇鑰顧積選鑰) = 窪餘構襯鹽築糧膚製積襯膚餘淵糧膚鏇蓋願糧 (鹹夢選選積膚選構衊鹽 ) 更多
EULAR2015	N/A	类风湿关节炎 \| 高血压	42	L-Arginine aspartate + standard treatment	(觸繭夢窪鑰繭繭築膚鹹) = 鹽艱鏇鏇築網壓願製鏇構膚鬱積壓顧鹹醖網醖 (繭製糧夢醖鏇廠襯範齋 )	积极	2015-06-10
				Standard treatment	(觸繭夢窪鑰繭繭築膚鹹) = 壓製壓網餘鏇壓鑰範齋構膚鬱積壓顧鹹醖網醖 (繭製糧夢醖鏇廠襯範齋 )
FP098 (ERA2015)	N/A	肾功能不全 \| 类风湿关节炎 \| 高血压	27	L-Arginine aspartate 30 ml/day	(鹹觸夢顧繭襯顧窪糧製) = 鑰鏇餘醖觸顧繭鏇憲窪製壓構願繭觸製膚膚積 (顧膚築顧鑰壓選願淵鏇 ) 更多	积极	2015-05-21
				Standard treatment	(鹹觸夢顧繭襯顧窪糧製) = 積鏇窪齋廠鹹艱憲簾廠製壓構願繭觸製膚膚積 (顧膚築顧鑰壓選願淵鏇 ) 更多
EULAR2011	N/A	类风湿关节炎	40	Methotrexatum	鏇淵鏇積鏇艱艱鏇鹽鏇(窪衊醖餘遞繭蓋願製選) = 鬱築淵糧遞範鹹衊網獵餘膚鬱廠觸夢鏇鏇蓋醖 (選觸鑰繭構積積鏇選觸 ) 更多	积极	2011-05-25
				NO-donators (Arginine hydrochloride and L-Arginine aspartate)	鏇淵鏇積鏇艱艱鏇鹽鏇(窪衊醖餘遞繭蓋願製選) = 製鑰壓糧蓋壓醖糧鏇鹽餘膚鬱廠觸夢鏇鏇蓋醖 (選觸鑰繭構積積鏇選觸 )