Sepsis is a fatal organ dysfunction caused by the uncontrolled inflammatory response of the host to infection. Excessive inflammatory reaction is the core factor in the occurrence and development of sepsis, the degree of organ dysfunction is directly related to the prognosis of sepsis. Timely intervention of excessive inflammatory response and alleviation of organ function damage are essential to improve the prognosis of sepsis. Maresin-1 (MaR-1) is a newly discovered endogenous specific pro-inflammatory resolution mediator, which plays a role of anti-inflammatory, pro-inflammatory regression and organ protection in sepsis, and may be a new target for the treatment of sepsis. This article reviews the research progress of the role of MaR-1 in the regulation of inflammation and organ protection in sepsis, in order to provide reference for the clinical development of new drugs for the treatment of sepsis.

2023-05-01·European review for medical and pharmacological sciences

Subfatin, asprosin, alamandine and maresin-1 in cerebral ischemia, intracranial and subarachnoid hemorrhages.

Article

作者: Kilinc, A ; Hanbeyoglu, O ; Erol, E ; Sahin, I ; Aydin, S ; Albayrak, S ; Ugur, K ; Aydin, M A ; Acar, V

OBJECTIVE:

Cerebrovascular diseases (CVDs) remain an important public health issue due to the increasing number of deaths worldwide. Changes in the synthesis and release of peptides in CVDs may play an important role in elucidating the physiopathology of the disease. Therefore, this study was to investigate the fate of maresin-1 (MaR-1), subfatin (SUB), asprosin (ASP), and alamandine (ALA) levels in patients with cerebral infarction (CI), intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH) evaluated within the scope of CVDs, and voluntary healthy controls.

PATIENTS AND METHODS:

The study participants were divided into 4 groups: CI patients, ICH patients, SAH patients, and healthy volunteers. The diagnosis of CVDs was made based on the National Institutes of Health Stroke Scale (NIHSS), Intracerebral Hemorrhage Score (ICHS), Botterel-Hunt-Hess Scale (BHHS), and cranial computed tomography (CT). The levels of MaR-1 (ng/mL), SUB (ng/mL), ASP (ng/mL), and ALA (pg/mL) in the blood samples collected from the participants were studied using the ELISA method. Other parameters included in the study were obtained from the patient records of our hospital.

RESULTS:

The comparison of MaR-1 [(control 1.38 ± 0.14), SAH (0.98 ± 0.087), CI (0.67 ± 0.04), ICH (0.51 ± 0.03)], SUB [(control (13.2 ± 1.4), SAH (10.1 ± 1.2), CI (7.9 ± 0.8), ICH (5.8 ± 0.5)], and ALA [(control (67.2 ± 7.9), SAH (58.2 ± 4.3), CI (42.1 ± 3.7), and ICH (34.2 ±3.9)] values revealed a significant decrease compared to the control values. The comparison of the ASP values of SAH, CI, and ICH patients and control values (11.6 ± 1.2) showed significantly higher asprosin values in SAH (13.8 ± 1.1), CI (15.4 ± 1.2) and ICH (28.9 ± 2.8) patients. Similarly, systolic blood pressure (SBP), diastolic blood pressure (DBP), and glucose levels of CKD patients were also high.

CONCLUSIONS:

Decreased MaR-1, SUB, ALA and increased ASP compared to the control values may play a role in the physiopathology of these diseases. MaR-1, SUB, ALA, and ASP differences between SAH, CI and ICH patients may also guide clinicians along with SBP, DBP and glucose values.

2023-01-01·Journal of inflammation research

Subfatin, Asprosin, Alamandine and Maresin-1 Inflammation Molecules in Cardiopulmonary Bypass.

Article

作者: Aydin, Suna ; Hanbeyoglu, Onur

Purpose:

Cardiopulmonary bypass (CPB) is a nonphysiological procedure in which inflammatory reactions and oxidative stress are induced, hormones and hemodynamic parameters are affected, and circulation is maintained outside the body. This study aimed to examine the effects of CPB on blood subfatin (SUB), asprossin (ASP), alamandine (ALA) and maresin-1 (MaR-1) levels.

Materials and Methods:

Controls and patients who underwent open-heart surgery with CPB and whose age and body mass indices were compatible with each other were included in the study. Venous blood samples were collected from CPB patients (n =19) before anesthesia induction (T1), before CPB (T2), 5 min before cross-clamp removal (T3), 5 min after cross-clamp removal (T4), when taken to the intensive care unit (T5), postoperative 24th hour (T6) and 72nd hour (T7) postoperatively. Venous blood was collected from the healthy controls (n =19). The amounts of SUB, ASP, ALA, and MaR-1 in the blood samples were measured using an Enzyme-Linked Immunosorbent Assay (ELISA).

Results:

The amounts of SUB and MaR-1 in the control group were significantly higher than those in CPB patients, while these parameters in T1-T3 blood gradually decreased in CPB patients (p<0.01). It was also reported that the amounts of ASP and ALA in the control group were significantly lower than those in CPB patients, whereas those parameters in the T1-T3 blood samples increased gradually in CPB patients, but started to decrease in T4-T7 blood samples.

Conclusion:

These hormonal changes in the organism due to CPB demonstrate that "hormonal metabolic adaptation" mechanisms may be activated to eliminate the negative consequences of surgery. According to these data, SUB, MaR-1, anti-alamandine, and anti-asprosin could be used in CPB surgeries may come to the fore in the future to increase the safety of CPB surgeries.

项与 MAR-001 相关的新闻（医药）

2024-06-24

·创鉴汇

13家创新药公司获融资！非降解分子胶疗法新锐完成2800万美元融资 | 一周融资

▎药明康德内容团队编辑据创鉴汇不完全统计，上周（6月17日至6月23日）全球大健康领域共披露融资事件25起，总额超60亿元。按照金额划分，亿元及以上融资9起。按照已披露的融资轮次划分，早期融资（B轮以前）6起，中后期融资（B轮及以后）9起。生物医药领域共13家公司获融资，涉及药物类型包括分子胶药物、mRNA药物、创新肿瘤免疫抑制剂等。 #01 Marea Therapeutics完成1.9亿美元融资关键词：心脏代谢疾病药物最新融资：1.9亿美元A轮及B轮本轮投资机构：Alpha Wave Global、Forbion、Omega Funds、Perceptive Xontogeny Venture Funds、Sofinnova等 6月19日，Marea Therapeutics宣布走出隐匿模式，并完成共1.9亿美元的A轮和B轮融资。Marea旨在开发用于治疗心脏代谢疾病的新一代药物，其用于降低残留胆固醇的潜在“first-in-class”主打项目MAR001目前正在2期试验受检视，这笔融资将用于资助该2期试验开发计划，以及其他管线项目的进一步推进。 Marea的主要项目MAR001是一种潜在"first-in-class"的单克隆抗体，靶向在脂肪组织中高度表达的ANGPTL4蛋白。MAR001通过抑制ANGPTL4，从而优先增强脂肪组织中的脂蛋白脂肪酶（LPL）活性，进而降低残留胆固醇，改善脂肪组织和代谢功能，并减少心血管事件。残留胆固醇由富含甘油三酯的脂蛋白所携带，会造成动脉粥样硬化，并在独立于传统风险因素（如低密度脂蛋白胆固醇、糖尿病或肥胖）下驱动心血管事件。目前尚无获批的靶向疗法来降低人体残留胆固醇的水平并改善代谢功能。 #02 iOnctura完成8000万欧元B轮融资关键词：肿瘤免疫抑制剂最新融资：8000万欧元B轮本轮投资机构：3B Future Health Fund、European Innovation Council、INKEF Capital、M Ventures 、Schroders Capital等 6月20日，iOnctura宣布完成8000万欧元的B轮融资。iOnctur正在开发一系列精准口服小分子抗癌药物。该公司已将两种候选疗法推进到中期临床开发阶段。主打在研药物roginolisib是一款PI3Kδ别构调节剂，具有独特的化学结构和结合模式。新闻稿指出，roginolisib有潜力成为首个成功靶向PI3Kδ关键癌症通路的治疗方法。此次融资将用于加速roginolisib用于治疗葡萄膜黑色素瘤（UM）的临床试验，这是一种眼部罕见癌症，目前可用的治疗方法很少。在一项1b期临床试验中，roginolisib在UM中表现出长期安全性和可喜的疗效，且在数月内持续保持临床活性。 #03 Elion Therapeutics完成8100万美元B轮融资关键词：抗侵袭性真菌感染药物最新融资：8100万美元B轮本轮投资机构：AMR Action Fund、Deerfield Management、Illinois Ventures 6月17日，生物技术公司Elion Therapeutics完成了由Deerfield Management和AMR Action Fund领投的8100万美元的B轮融资。该公司是致力于转变危及生命的侵袭性真菌感染（IFI）治疗方法的生物技术公司，主要研究方向是开发旨在降低毒性的下一代多烯抗真菌药物SF001。目前，SF001正在进行多次递增剂量研究，其活性分子是抗真菌药物两性霉素B的新型类似物，可减轻全身毒性。该轮融资资金将继续用于推进SF001的临床试验和研发。 #04 Iambic Therapeutics获得5000万美元融资关键词：人工智能药物发现最新融资：5000万美元B轮本轮投资机构：Abingworth、Coatue Management、Exor Ventures、Illumina Ventures、Mubadala Capital 6月18日，Iambic Therapeutics宣布完成5000万美元的B轮扩展融资。获得资金将用于推进Iambic的临床期和临床前项目，包括IAM1363，一种高度选择性、可穿越血脑屏障的HER2抑制剂。它可以抑制野生型和携带致癌突变的HER2受体，目前处于1/1b期研究中。获得资金还将用于开发一种潜在“first-in-class”的CDK2/4抑制剂，旨在扩大治疗窗口并解决乳腺癌等实体瘤中的耐药问题。Iambic的候选药物是使用其AI蛋白结构预测和整体药物设计模型发现的。这些技术集成在一个闭环、自动化、高通量的生物和化学实验平台中，每周从数千种分子设计中提供新的生物学见解，从而直接为其AI模型提供信息。 #05 Rapafusyn获2800万美元A轮融资关键词：非降解分子胶最新融资：2800万美元A轮本轮投资机构：本草资本、比邻星创投、龙磐资本 6月20日，瑞福信医药科技（Rapafusyn Pharmaceuticals，简称“瑞福信”或“Rapafusyn”）宣布完成A轮追加轮次融资的初步交割，A轮总融资额达2800万美元。Rapafusyn为基于非降解分子胶的创新药物发现及开发公司。本次融资将用于该公司基于大环环肽的非降解分子胶技术平台发展和针对广泛疾病种类的创新药管线推进，并进一步提升其内部新药研发能力。 Rapafusyn诞生于约翰·霍普金斯大学（Johns Hopkins University）药理学和分子科学教授刘钧（Jun O. Liu）博士的实验室，在2015年由刘钧教授和严圣军博士共同创建，是新一代双功能大环类药物研发平台公司，旨在开发非降解分子胶以解决难成药靶点的问题，改善患者治疗效果。读者们请星标⭐创鉴汇，第一时间收到推送免责声明：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。版权说明：本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转发/复制至其他平台。转发授权请在「创鉴汇」微信公众号留言联系我们。更多数据内容推荐点击“在看”，分享创鉴汇健康新动态

临床2期临床1期引进/卖出信使RNA

2024-06-20

·药明康德

开发潜在“first-in-class”降胆固醇疗法！新锐完成1.9亿美元A、B轮融资

6月19日，由Third Rock Ventures孵化的Marea Therapeutics走出隐匿模式，并完成共1.9亿美元的A轮和B轮融资。Marea旨在开发用于治疗心脏代谢疾病的新一代药物，其用于降低残留胆固醇的潜在“first-in-class”主打项目MAR001目前正在2期试验受检视，这笔融资将用于资助该2期试验开发计划，以及其他管线项目的进一步推进。 A轮融资由Third Rock Ventures领投，B轮融资则由Sofinnova Investments领投，Forbion、Perceptive Xontogeny Venture Fund和venBio共同领投，Alpha Wave Global、Omega Funds、Surveyor Capital和创始投资者Third Rock Ventures也参与其中。 Marea的主要项目MAR001是一种潜在"first-in-class"的单克隆抗体，靶向在脂肪组织中高度表达的ANGPTL4蛋白。MAR001通过抑制ANGPTL4，从而优先增强脂肪组织中的脂蛋白脂肪酶（LPL）活性，进而降低残留胆固醇，改善脂肪组织和代谢功能，并减少心血管事件。残留胆固醇由富含甘油三酯的脂蛋白所携带，会造成动脉粥样硬化，并在独立于传统风险因素（如低密度脂蛋白胆固醇、糖尿病或肥胖）下驱动心血管事件。目前尚无获批的靶向疗法来降低人体残留胆固醇的水平并改善代谢功能。人类遗传学已证明ANGPTL4是一个非常有前景用于降低残留胆固醇的治疗靶点，其等位基因的抑制可导致残留胆固醇的清除、甘油三酯分布的改善、胰岛素敏感性的提高，并可通过脂肪特异性机制防护心血管疾病和2型糖尿病。MAR001在1期临床试验中表现出积极结果，单剂量MAR001显著降低受试者的残留胆固醇水平并改善其代谢疾病相关生物标志物。该疗法目前正在代谢功能障碍成人患者中进行2期临床研究。参考资料： [1] Marea Therapeutics Launches with $190 Million to Accelerate a New Generation of Medicines for Cardiometabolic Diseases. Retrieved June 18, 2024 from https://www.businesswire.com/news/home/20240617273647/en/Marea-Therapeutics-Launches-with-190-Million-to-Accelerate-a-New-Generation-of-Medicines-for-Cardiometabolic-Diseases 内容来源于网络，如有侵权，请联系删除。

临床研究临床1期

2024-06-19

·Pharmaceutical Technology

Marea launches with $190m to develop cardiometabolic therapies

The asset aims to enhance the activity of lipoprotein lipase in adipose tissue, which is expected to reduce cardiovascular events. Credit: OlgaKraemer / Shutterstock. Clinical-stage biotechnology company Marea Therapeutics has launched with funding of $190m secured through combined Series A and B rounds to develop cardiometabolic disease treatments. Third Rock Ventures spearheaded the Series A financing round while the Series B round was led by Sofinnova Investments. Co-leading the Series B round were Forbion and the Perceptive Xontogeny Venture Fund, alongside venBio. Contributing participants were Alpha Wave Global, Omega Funds, Surveyor Capital and Third Rock Ventures, the founding investor. These investments will be used to advance the Phase II development of MAR001 and additional pipeline programmes. A lead programme of the company, MAR001 is a monoclonal antibody that targets ANGPTL4, a protein prevalent in adipose tissue. See Also: FDA grants approval for Alexion’s NMOSD treatment AbbVie signs agreement to acquire Landos Biopharma for $212.5m By hindering ANGPTL4, the asset aims to enhance the activity of lipoprotein lipase in adipose tissue, which is expected to lower remnant cholesterol levels, enhance metabolic function and potentially reduce cardiovascular events. Remnant cholesterol, which is associated with triglyceride-rich lipoproteins, is known for its atherogenic properties and its role in driving cardiovascular events, independent of other risk factors such as diabetes, LDL cholesterol or obesity. There are currently no targeted therapies available to lower remnant cholesterol and improve metabolic function. In preclinical models, MAR001 demonstrated promising results, including triglyceride reductions, remnant cholesterol and ectopic fat, as well as improved insulin sensitivity. Following robust Phase I outcomes, the antibody progressed to Phase II clinical development for adults with metabolic dysfunction. Marea CEO Josh Lehrer stated: “Marea aims to transform the way cardiometabolic diseases are treated by leveraging large-scale human genetics and expertise in adipose function and biology to pursue genetically validated targets focusing on central – but unaddressed – drivers of cardiometabolic disease risk. “This approach could be the next frontier for patients with cardiometabolic disease who remain at very high risk, despite currently available therapies.”