更新于：2024-11-01

secretin

更新于：2024-11-01

基本信息

别名

SCT、secretin

简介

Hormone involved in different processes, such as regulation of the pH of the duodenal content, food intake and water homeostasis (PubMed:25332973). Exerts its biological effects by binding to secretin receptor (SCTR), a G-protein coupled receptor expressed in the basolateral domain of several cells (PubMed:25332973). Acts as a key gastrointestinal hormone by regulating the pH of the duodenal content (By similarity). Secreted by S cells of the duodenum in the crypts of Lieberkuehn and regulates the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate (NaHCO(3)) from the ductal cells of the pancreas (By similarity). Production of bicarbonate is essential to neutralize the pH and ensure no damage is done to the small intestine by the gastric acid (By similarity). In addition to regulating the pH of the duodenal content, plays a central role in diet induced thermogenesis: acts as a non-sympathetic brown fat (BAT) activator mediating prandial thermogenesis, which consequentially induces satiation (Probable). Mechanistically, secretin released by the gut after a meal binds to secretin receptor (SCTR) in brown adipocytes, activating brown fat thermogenesis by stimulating lipolysis, which is sensed in the brain and promotes satiation (By similarity). Also able to stimulate lipolysis in white adipocytes (By similarity). Also plays an important role in cellular osmoregulation: released into the systemic circulation in response to hyperosmolality and acts at different levels in the hypothalamus, pituitary and kidney to regulate water homeostasis (By similarity). Also plays a role in the central nervous system, possibly by acting as a neuropeptide hormone: required for hippocampal synaptic function and neural progenitor cells maintenance (By similarity).

关联

项与 secretin 相关的药物

SCT-5-27

靶点

secretin

作用机制

secretin拮抗剂

在研机构

The Texas A&M University System [+1]

原研机构

The Texas A&M University System

在研适应症

原发性硬化性胆管炎

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

100 项与 secretin 相关的临床结果

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100 项与 secretin 相关的转化医学

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0 项与 secretin 相关的专利（医药）

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2,319

项与 secretin 相关的文献（医药）

2024-11-01·Neurochemical Research

Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism

Article

作者: Varman, Durairaj Ragu ; Saavedra-Bonilla, Hugo ; Reyes-Haro, Daniel

AbstractAutism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.

2024-08-27·Scandinavian Journal of Pain

A positive scratch collapse test in anterior cutaneous nerve entrapment syndrome indicates its neuropathic character

Article

作者: Scheltinga, Marc R. M. ; Schaap, Lotte ; Jacobs, Monica L. Y. E. ; Roumen, Rudi M. H. ; ten Have, Tom

AbstractObjectivesChronic abdominal pain is occasionally caused by an abdominal wall entity such as anterior cutaneous nerve entrapment syndrome (ACNES). This syndrome is thought to occur due to intercostal nerve branches (T7–12) that are entrapped in the rectus abdominis muscles. The diagnosis is largely based on subjective clues in patient history and physical examination. A test referred to as the scratch collapse test (SCT) is used as an additional diagnostic tool in peripheral nerve entrapment syndromes such as the carpal tunnel syndrome. The aim of the present study is to investigate whether an SCT was positive in patients with suspected ACNES. If so, this finding may support its hypothesized neuropathic character.MethodsA prospective, case–control study was performed among patients with ACNES (n = 20) and two control groups without ACNES (acute intra-abdominal pathology n = 20; healthy n = 20), all were consecutively included. ACNES was diagnosed based on previously published criteria. The SCT test was executed at the painful abdominal area in both patient groups and at a corresponding area in healthy controls. Predictive values, sensitivity, and specificity were calculated. Videos of tests were evaluated by blinded observers.ResultsSCT was judged positive in 19 of 20 ACNES patients but not in any of the 40 controls. A 95% sensitivity (confidence interval [CI]: 75–99) and optimal specificity (100%; CI: 83–100) were calculated.ConclusionsThe positive SCT supports the hypothesis that ACNES is an entrapment neuropathy. A positive SCT should be considered a major diagnostic criterion for ACNES.

2024-06-20·European Thyroid Journal

The role of [18F]F-DOPA PET/CT in diagnostic and prognostic assessment of medullary thyroid cancer: a 15-year experience with 109 patients

Article

作者: Crevenna, Richard ; Li, Shuren ; Karanikas, Georgios ; Yu, Josef ; Jiang, Zewen ; Hargitai, Lindsay ; Hacker, Marcus ; Rainer, Eva ; Traub-Weidinger, Tatjana ; Zhang, Zhaoqi

ObjectiveCorrect diagnosis and prognostic evaluation of medullary thyroid cancer (MTC) are crucial to treat patients. The purpose of this study was to evaluate the diagnostic and prognostic value of [18F]F-DOPA PET/CT in patients with MTC.MethodsWe reviewed MTC patients who underwent [18F]F-DOPA PET/CT from June 2008 to November 2023. Clinical characteristics, follow-up data, and the following [18F]F-DOPA PET/CT parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and SUVmean of multiple organs. The diagnostic value of PET/CT for the detection of tumor lesions was calculated. Serum basal calcitonin (bCt) and stimulated calcitonin (sCt) were determined. Receiver operating characteristics, Kaplan–Meier, and Cox regression analyses were performed.ResultsIn total, 109 patients (50 women, 59 men; average age, 55 ± 14 years) were included in the analysis. The patient-related sensitivity, specificity, and accuracy of [18F]F-DOPA PET/CT were 95%, 93%, and 94%, respectively. The lesion-related sensitivity, specificity, and accuracy were 65%, 99%, and 72%, respectively. The optimal cutoff values of bCt, sCt, and CEA to obtain positive [18F]F-DOPA PET/CT results were 64 pg/mL, 1808 pg/mL, and 4 µg/L, respectively. Patients with negative [18F]F-DOPA PET/CT had longer overall survival than patients with positive [18F]F-DOPA PET/CT results (P = 0.017). Significant positive correlations were found between bCt, sCt, and CEA with SUVmax, SUVmean, and MTV of [18F]F-DOPA PET/CT (P < 0.001). [18F]F-DOPA PET/CT results and MTV may be useful for the evaluation of the prognosis of patients with recurrent MTC, while age and MTV were independent prognostic factors in patients with primary MTC. For all patients, SUVmean of the left kidney, liver, aorta, and pancreas might be used to independently predict OS.Conclusion[18F]F-DOPA PET/CT had great value for diagnosis and prognostic assessment in patients with MTC. The DOPA PET/CT parameter SUVmean and MTV showed significant association with OS.

项与 secretin 相关的新闻（医药）

2024-04-15

·药智网

地域创新药新政“菜单”，正在预制中

近日，北京市医疗保障局等9部门发布《北京市支持创新医药高质量发展若干措施（2024）（征求意见稿）》，“地域创新药新政”再次被推上风口浪尖，一份关于创新药新政的“特色菜单”，正在预制中。01创新药迎利好，涉及北京百余家药企新药研发是对时间和资金的双重考验，两者又互为影响，据前瞻产业研究院报告显示，创新药从研发到批准上市需经历9.5-15年，投入资金在23-27亿美元。图1 创新药研发生产流程图片来源：前瞻产业研究院国内监管机构从2015年7月开始出台改革措施，缓解了创新药申请积压，同时鼓励创新药物开发，与改革前（2010年1月至2015年6月）相比，改革后（2015年7月至2020年12月）的IND审批时间缩短了414天，NDA审批时间缩短了441天，2018年7月开始，NMPA将药物临床试验审批程序调整为默示许可制度，但从整个临床试验阶段的长度而言，改革后和改革前的差异并不显著（2572天vs 2688天）。如果说资金是压倒创新药研发“骆驼”的硬“压强”，那么，时间就是压倒“骆驼”的软“刀子”，时间周期的长短，在很大程度上决定着资金的多少，以及资金链的松紧。《北京市支持创新医药高质量发展若干措施2024（征求意见稿）》对创新药最大的影响就是时间上的“照顾”，将临床试验启动整体用时压缩至28周以内，并持续加速；推动实施“药品补充申请审评时限从200日压缩至60日、药品临床试验审批时限从60日压缩至30日”的国家创新试点。值得一提的是，将对创新药企实施重点项目制管理机制，在注册申报、许可办理等方面“一品一策”、提前介入、全程指导，“保姆”式的服务也将为创新药的研发扫清时间上的障碍。此外，在支付端，将治疗费用较高的国谈药品纳入按固定比例支付，减轻参保人员费用负担；对符合条件的新药新技术费用，不计入DRG病组支付标准，单独支付；鼓励商业保险公司与医疗机构、医药企业合作，并建立“北京普惠健康保”特药清单动态调整机制，为创新药上市后的成本回收打通渠道。据药智数据企业版——区域产业分析系统查询显示，北京地区主营业务为化药的企业有265家，中药企业有131家，生物制品企业有129家，原料药企业有14家，共计539家。北京的创新药（含改良新药）申请临床及批准临床数量在2019年以来就呈持续增长趋势，2023年分别达185个和149个。图2 2016年以来，北京创新药及改良新药临床情况图片来源：药智数据若征求意见稿顺利通过，北京又将迎来一波新药研发的高潮。此外，在疾病领域方向，将有多个疾病领域的药品及药企占据“地利”因素，肿瘤领域最多。作为肿瘤药物研发先锋，百济神州旗下产品泽布替尼2023年全球销售额达到近13亿美元，成为国产创新药首个“十亿美元分子”。此外，上述药企中，多数在肿瘤领域同样有创新药布局，如四环医药、神州细胞、中国医药、诺诚健华、华夏生生药业、祐和医药、加科思等，就连专注于糖尿病代谢领域的甘李药业，也布局的有肿瘤新药GLR2007。值得一提的是，四环医药在肝病领域，神州细胞在罕见病、HPV疫苗和银屑病，中国医药在勃起功能障碍，诺诚健华在自免疾病领域，华夏生生药业在肝炎，舒泰神在汗腺炎、癌痛、哮喘和罕见病，都有创新药布局。而作为与百济神州一样专注某个固定领域的甘李药业，在糖尿病代谢领域也将迎来空前的发展机遇。历经磨难的CXO，部分企业终能扳回一局。近年来，受美国政策，以及韩国CXO抢单的影响，加上创新药的持续“寒冬”，CXO行业可谓是历经波折，在北京不乏康龙化成和阳光诺和等CXO药企。北京创新医研发新政，将为CXO药企承接国外创新药进入中国市场的临床订单提供更大的便利，CXO资本市场信心也将逐步恢复。02管线产品丰富，创新药研发哪家强？百济神州进入临床阶段的自研产品管线中，有Sonrotoclax、欧司珀利单抗、BGB-A445、BGB-16673、BGB-21447等13款产品，其中，Somrotoclax和欧司珀利单抗已处于3期临床阶段。图3 百济神州自研产品管线图片来源：百济神州公告Sonrotoclax是第二代BCL-2抑制剂,此前已获美国FDA授予治疗AML、MM、WM和MCL孤儿药认定，且有多项研究在2023年第65届美国血液学会（ASH）年会上展示。据1/2期研究数据显示，初治（TN）CLL/SLL患者接受Sonrotoclax联合泽布替尼治疗，耐受性良好，且未出现肿瘤溶解综合征（TLS）病例，缓解率达到100%，无患者出现疾病进展（PFS）。此外，Sonrotoclax单药治疗R/R边缘区淋巴瘤患者ORR为67%（n=8），其中4名患者(33%)达到完全缓解(CR)；640mg组ORR为78%(n=7)，其中4名患者(44%)达到CR；在先前接受BTK治疗时出现进展的所有4名患者中均观察到PR或更好缓解。甘李药业的创新药管线产品虽然不多，只有GZR18（片）、GZR101、GZR4和GLR2007等4款，但每款产品对其今后的发展都有着极为重要的作用。GZR101是甘李药业自主研发的新型预混双胰岛素复方制剂，由在研的长效基础胰岛素GZR33（50%）与速效门冬胰岛素（50%）混合制成，截至2023年12月，全球已上市的双胰岛素产品仅有诺和诺德的Ryzodeg；GZR4是第四代胰岛素，为每周皮下注射给药一次的超长效胰岛素周制剂，目前，全球范围内尚未有胰岛素周制剂产品被批准上市，进展最快的是诺和诺德的胰岛素周制剂Icodec，2024年3月，欧洲CHMP通过一项积极意见，建议批准Icodec用于治疗成人糖尿病。甘李药业作为深耕糖尿病领域的药企，胰岛素产品对其业绩有着重要的支撑，营收主要来自胰岛素制剂及胰岛素干粉的销售收入，因此，胰岛素产品的更新升级对甘李药业来说，是其能否在糖尿病领域继续立足的根本。神州细胞在创新药上的布局横跨罕见病、肿瘤、眼病及新冠等多个领域，包括2023半年报显示的SCT800、SCT200、SCT-I10A、SCT1000、SCT510A、SCTV01、SCT650C，以及近期获批临床的SCTC21C和SCTB35。图4 神州细胞在研项目图片来源：神州细胞2023半年报SCT800是治疗罕见病甲型血友病的首个国产重组八因子产品，也是神州细胞的首款上市产品，于2021年7月获批上市，据2022年报显示，首个完整年度销售收入为10.23亿元，而神州细胞当年收入全部来源于此。据2023年报显示，该产品销售额继续大幅增长，销售额约17.8亿元，同比增长超77%，且神州细胞营收依然主要来自于该药，营收同比增长84.46%，达18.87亿元。在神州细胞的创新药管线上，还有一款潜在的超爆款产品SCT1000，为全球首个进入临床的14价HPV疫苗，目前已处于3期临床试验阶段。虽然国产HPV疫苗早已上市，但面对进口9价HPV疫苗在解决供应端不足及年龄扩展后的的强势，高价HPV疫苗依然受到接种者追捧，神州细胞的SCT1000也被誉为最有实力打破进口高价HPV疫苗的选手之一。北京地区药企的创新药亮点颇多，在这里就不一一列举。03结语在2024年政府工作报告中，创新药首次被提及，充分表明了国家对创新药的决心及信心，随着北京等地创新药新政的推进，全国范围各具特色的创新药新政“菜单”即将来袭。参考来源：1.相关药企官网、公告及半年报、年报2.健康界《Nature系列综述：中国创新药研发趋势》3.前沿产业研究院《2023年中国创新药行业全景图谱》声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 金银花转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是昨天最受欢迎的文章哦

临床申请申请上市

2023-03-21

·生物谷

重大医学发现！程涛团队破解造血干细胞移植患者造血再生机制

该研究深度解析了HSPCs在allo-HSCT各阶段的调控过程，为allo-HSCT后可能出现的PGF、免疫重建差异和GVHD等提供了有效的参考依据。 2023年3月17日，中国医学科学院血液学研究所程涛教授团队联合郝莎副研究员和姜尔烈主任医师在 Science Immunology 在线发表了题为“Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation”的论文，首次揭示了异基因HSCT（allo-HSCT）移植后患者体内的造血干祖细胞（HSPCs）与成熟细胞的造血再生机制，提出了移植后免疫重建差异的时间窗口和鉴定aGVHD高风险患者的潜在指标。为了解异基因HSCT（allo-HSCT）如何实现对造血干祖细胞（HSPCs）与成熟细胞的调控，该研究利用单细胞标记逆转录RNA测序法（STRT-seq）和10×Genomics平台的3’端单细胞转录组测序对经流式分选后的Lin-CD34+细胞和TNCs细胞进行了测序。基于转录组特征的区别，作者将Lin-CD34+细胞分为10个类群。通过对HSPCs进行动力学分析，作者发现Donor中HSC/MPPs和LMPPs比例增加，而其占比在移植后重建的过程中下降。值得注意的是，移植患者自移植60天（d60）后，HSPCs组成开始出现差异。接着，作者对6名移植患者移植后的BM/外周血（PB）细胞进行了单细胞转录组嵌合分析。通过对收集的随访结果进行分析，作者发现Lin-CD34+细胞中只有大约1%的细胞为受者遗留细胞，其中85.7%为基质细胞，TNCs中中性粒细胞和T细胞占据了大多数。基于此，作者建立了基于单细胞测序的供受体区分方法。随后，作者在排除了受者遗留细胞的影响后，对HSC/MPPs、寡能祖细胞和单能的中性粒细胞祖细胞进行了比较分析，结果显示HSC/MPPs与寡能祖细胞表现出强烈的增殖倾向。此外，该研究还发现了具有特殊免疫调控表达谱的粒系祖细胞S100Ahigh Neus，其在G-CSF动员后富集，且在移植患者体内长期存在。随后的前瞻性队列研究（n=32）结果显示，没有aGVHD的患者体内的S100Ahigh Neu2含量明显高于发生aGVHD的患者。总而言之，该研究深度解析了HSPCs在allo-HSCT各阶段的调控过程，为allo-HSCT后可能出现的PGF、免疫重建差异和GVHD等提供了有效的参考依据。为临床预防移植患者发生免疫重建不良反应及aGVHD干预提供了重要医学见解。