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Caspases in PANoptosis PANoptosis中的半胱天冬酶
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1016/j.retram.2025.103502
Kaiyuan Song , Yongbin Wu , Sipin Tan
Recent studies prove that the three well-established cell death pathways—pyroptosis, apoptosis, and necroptosis—are not isolated but rather engage in extensive crosstalk. PANoptosis, a newly identified pathway of inflammatory regulated cell death (RCD), integrates characteristics of apoptosis, pyroptosis, and necroptosis. Caspases are a family of conserved cysteine proteases that play critical roles in pyroptosis, apoptosis, and necroptosis. Similarly, caspases also play a role in PANoptosis. In this paper, we review the molecular mechanisms of these three RCDs and the crosstalk between them. We also delineate the discovery of PANoptosis and its association with disease. Furthermore, we discuss the caspase function in PANoptosis, mainly focusing on caspase-6 and caspase-8 molecules. This review describes the key molecules, especially caspases, in the context of PANoptosis research, aiming to provide a foundation for targeted interventions in PANoptosis-associated diseases.
最近的研究证明,三种公认的细胞死亡途径——焦亡、凋亡和坏死并不是孤立的,而是相互联系的。PANoptosis是一种新发现的炎症调节细胞死亡(RCD)途径,融合了细胞凋亡、焦亡和坏死的特征。半胱天蛋白酶是一个保守的半胱氨酸蛋白酶家族,在焦亡、凋亡和坏死坏死中起关键作用。同样,caspases也在PANoptosis中发挥作用。本文综述了这三种rcd的分子机制以及它们之间的串扰。我们还描述了PANoptosis的发现及其与疾病的关系。此外,我们讨论了caspase在PANoptosis中的功能,主要集中在caspase-6和caspase-8分子上。本文综述了PANoptosis研究中的关键分子,特别是半胱天冬酶,旨在为PANoptosis相关疾病的靶向干预提供基础。
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引用次数: 0
Non-hematological triggers of VEXAS syndrome: A case report and literature review VEXAS综合征的非血液学诱因:1例报告及文献复习。
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1016/j.retram.2024.103487
Thibaud Loupret, Laurie De Coster, Camille Lemaçon, Emma Gadon, Philippe Bertin, Pascale Vergne-Salle
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引用次数: 0
A comparison of porcine anti-human T lymphocyte immunoglobulin, rabbit-ATG for GVHD prophylaxis and without ATG in matched sibling donor transplantation 猪抗人T淋巴细胞免疫球蛋白与兔ATG预防GVHD的比较
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1016/j.retram.2025.103501
Shiyuan Zhou , Chao Ma , Danping Zhou , Qian Zhu , Wenjuan Zhu , Jing Li , Depei Wu , Xiao Ma , Xiaojin Wu

Introduction

Research on anti-lymphocyte globulins other than rabbit anti-thymocyte globulin (r-ATG) in prevention of graft-versus-host-disease (GVHD) following HLA-matched siblings hematopoietic stem cell transplantation (MSD-HSCT) is limited. The objective of this study is to investigate the distinct impacts of porcine anti-human T lymphocyte immunoglobulin (p-ATG) and r-ATG on outcomes of MSD-HSCT in patients with hematologic malignancies.

Patients and methods

This retrospective analysis enrolled 373 consecutive patients who underwent MSD-HSCT from January 2019 to October 2023. 135 patients received r-ATG (5mg/kg) and 51 received p-ATG (30mg/kg) for GVHD prophylaxis. 187 did not receive r-ATG or p-ATG.

Results

Despite early deaths, no engraftment failure occurred. In the r-ATG group, neutrophil engraftment was observed earlier, while platelet engraftment was delayed compared to other groups. Both r-ATG and p-ATG group showed protective effect on chronic graft-versus-host disease (cGVHD) (13.9 % and 29.6 % respectively vs. 43.0 % of control group at 2 years post HSCT), whereas only the r-ATG group displayed a decreased acute GVHD (aGVHD) rate (24.9 % vs. 39.8 % of control group at day 100 post HSCT). GVHD-free and relapse-free survival (GRFS) were found superior in both r-ATG and p-ATG groups (63.4 % and 56.8 % respectively vs. 37.0 % of control group at 2 years post HSCT). R-ATG was identified as an independent protective factor for aGVHD, cGVHD and GRFS in multivariate analysis.

Conclusions

Our study further confirmed the role of ATG in MSD-HSCT for improving the outcomes. No evidence supported substituting r-ATG with p-ATG in achieving these effects in the study.
除兔抗胸腺细胞球蛋白(r-ATG)外,抗淋巴细胞球蛋白在hla匹配的兄弟姐妹造血干细胞移植(MSD-HSCT)后预防移植物抗宿主病(GVHD)中的研究有限。本研究的目的是探讨猪抗人T淋巴细胞免疫球蛋白(p-ATG)和r-ATG对血液恶性肿瘤患者MSD-HSCT结果的不同影响。患者和方法本回顾性分析纳入了373例连续患者,这些患者于2019年1月至2023年10月期间接受了MSD-HSCT。135例患者接受r-ATG (5mg/kg)治疗,51例接受p-ATG (30mg/kg)治疗预防GVHD。187例未接受r-ATG或p-ATG治疗。结果除早期死亡外,未发生移植失败。与其他组相比,r-ATG组中性粒细胞着床时间提前,血小板着床时间延迟。r-ATG和p-ATG组对慢性移植物抗宿主病(cGVHD)均有保护作用(移植后2年分别为13.9%和29.6%,对照组为43.0%),而只有r-ATG组显示急性移植物抗宿主病(aGVHD)发生率降低(移植后100天为24.9%,对照组为39.8%)。r-ATG组和p-ATG组的无gvhd和无复发生存率(GRFS)在HSCT后2年分别为63.4%和56.8%,对照组为37.0%。多因素分析发现R-ATG是aGVHD、cGVHD和GRFS的独立保护因素。结论本研究进一步证实了ATG在MSD-HSCT中改善预后的作用。在研究中,没有证据支持用p-ATG代替r-ATG达到这些效果。
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引用次数: 0
Non-valvular atrial fibrillation following COVID-19 in a young female with FGFR3 mutation: A challenging concern FGFR3突变的年轻女性在COVID-19后发生非瓣膜性房颤:一个具有挑战性的问题
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1016/j.retram.2025.103497
Sawsan Ismail , Firas Hamed , Tamim Alsuliman , Kanaan Al-Tameemi
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引用次数: 0
Accelerating CAR T cell manufacturing with an automated next-day process 加速CAR - T细胞的自动化生产。
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1016/j.retram.2024.103489
Moloud Ahmadi, Nicholas Putnam, Max Dotson, Danny Hayoun, Jasmine Padilla, Nujhat Fatima, Prajakta Bhanap, Gertrude Nonterah, Xavier de Mollerat du Jeu, Yongchang Ji
The traditional method of CAR T cell production involves lengthy ex-vivo culture times which can result in the reduction of crucial naïve T cell subsets. Moreover, traditional CAR T cell therapy manufacturing processes can prolong time-to-patient, potentially delaying patient treatment, and contribute to disease progression. In this study, we describe an innovative and semi-automated 24-hour CAR T manufacturing process that yields a higher percentage of naïve/stem-cell like T cells which showed high cytotoxic activity and cytokine release in vitro. The data supports the feasibility of implementing this streamlined manufacturing process in clinics. This approach also has the potential to enhance CAR T therapy efficacy and improve patient access to therapy.
传统的CAR - T细胞生产方法涉及较长的离体培养时间,这可能导致关键naïve T细胞亚群的减少。此外,传统的CAR - T细胞疗法制造工艺可能会延长到患者的时间,可能会延迟患者的治疗,并导致疾病进展。在这项研究中,我们描述了一种创新的半自动化的24小时CAR - T制造工艺,该工艺产生更高百分比的naïve/干细胞样T细胞,这些细胞在体外显示出高细胞毒活性和细胞因子释放。数据支持在诊所实施这种流线型制造过程的可行性。这种方法也有可能提高CAR - T疗法的疗效,并改善患者获得治疗的机会。
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引用次数: 0
CAR-iNKT cell therapy: mechanisms, advantages, and challenges CAR-iNKT细胞疗法:机制、优势和挑战。
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1016/j.retram.2024.103488
Zixuan Wang , Guangji Zhang
In recent years, chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking approach in cancer immunotherapy. Particularly in hematologic malignancies, such as B-cell acute lymphoblastic leukemia (B-ALL), B cell lymphomas and multiple myeloma. CAR-T therapy has demonstrated remarkable clinical efficacy, leading to the approval of several CAR-T cell products and offering significant benefits to numerous leukemia patients. Despite these successes, the application of CAR-T cells in solid tumors remains limited due to significant challenges, including immunosuppressive tumor microenvironments, heterogeneous antigen expression, and treatment-associated toxicities. In parallel with CAR-T development, researchers are investigating other immune cell platforms to overcome these obstacles. Among these, invariant natural killer T (iNKT) cells have garnered increasing attention for their unique immunological properties. Unlike conventional T cells, iNKT cells are a subset of T lymphocytes characterized by the expression of a semi-invariant T-cell receptor (TCR) that recognizes lipid antigens presented by CD1d molecules. This distinctive antigen recognition mechanism enables iNKT cells to bridge innate and adaptive immunity, granting them potent antitumor activity and the ability to modulate the tumor microenvironment. Additionally, iNKT cells exhibit intrinsic resistance to exhaustion and an enhanced ability to infiltrate solid tumors compared to traditional T cells. Building on these properties, researchers are leveraging CAR technology to enhance iNKT cell tumor-targeting capabilities, aiming to overcome barriers encountered in solid tumor therapy. This review provides an in-depth discussion of the application and therapeutic potential of CAR-iNKT cells in cancer immunotherapy, with a focus on their advantages over conventional CAR-T cells and their role in addressing the challenges of solid tumor treatment.
近年来,嵌合抗原受体(CAR) t细胞治疗已成为癌症免疫治疗的一种突破性方法。特别是在血液恶性肿瘤,如B细胞急性淋巴细胞白血病(B- all), B细胞淋巴瘤和多发性骨髓瘤。CAR-T疗法已经显示出显著的临床疗效,导致几种CAR-T细胞产品被批准,并为众多白血病患者提供了显着的益处。尽管取得了这些成功,CAR-T细胞在实体肿瘤中的应用仍然有限,因为存在重大挑战,包括免疫抑制肿瘤微环境、异质抗原表达和治疗相关的毒性。在CAR-T发展的同时,研究人员正在研究其他免疫细胞平台来克服这些障碍。其中,不变性自然杀伤T细胞(iNKT)因其独特的免疫学特性而受到越来越多的关注。与传统T细胞不同,iNKT细胞是T淋巴细胞的一个亚群,其特征是一个半不变T细胞受体(TCR)的表达,该受体识别CD1d分子呈递的脂质抗原。这种独特的抗原识别机制使iNKT细胞能够架起先天免疫和适应性免疫的桥梁,赋予它们强大的抗肿瘤活性和调节肿瘤微环境的能力。此外,与传统的T细胞相比,iNKT细胞表现出固有的抗衰竭和浸润实体肿瘤的能力增强。基于这些特性,研究人员正在利用CAR技术来增强iNKT细胞肿瘤靶向能力,旨在克服实体肿瘤治疗中遇到的障碍。本文对CAR-iNKT细胞在癌症免疫治疗中的应用和治疗潜力进行了深入的讨论,重点讨论了CAR-iNKT细胞相对于传统CAR-T细胞的优势及其在解决实体肿瘤治疗挑战中的作用。
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引用次数: 0
Unraveling misinterpretations in pediatric COVID-19 admission trends: The Impact of CDC Reporting Changes 消除对儿童COVID-19入院趋势的误解:疾病预防控制中心报告变化的影响
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1016/j.retram.2024.103490
Yoshiyasu Takefuji
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引用次数: 0
Thanks to reviewers 感谢审稿人
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1016/j.retram.2025.103507
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引用次数: 0
Evaluation and management of hepatic dysfunction, portal hypertension and portal/splanchnic vein thrombosis in patients with myelofibrosis undergoing allogeneic haematopoietic cell transplantation: A practice based survey on behalf of the Chronic Malignancies Working Party of the EBMT. 接受异基因造血细胞移植的骨髓纤维化患者肝功能异常、门静脉高压和门静脉/细静脉血栓形成的评估和管理:代表 EBMT 慢性恶性肿瘤工作组进行的基于实践的调查。
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2024-10-29 DOI: 10.1016/j.retram.2024.103476
Giorgia Battipaglia, Nicola Polverelli, Joe Tuffnell, Patrizia Chiusolo, Marie Robin, Massimiliano Gambella, Annoek Broers, Elisa Sala, Jakob Passweg, Sabine Furst, Lone Smidtrup Friis, Remy Dulery, Moniek de Witte, Micha Srour, Maria Chiara Finazzi, Claudia Wehr, Arnon Nagler, Deborah Richardson, Wolfgang Bethge, Andrew Clark, Joanna Drozd-Sokolowska, Kavita Raj, Tomasz Czerw, Juan Carlos Hernández-Boluda, Donal P McLornan

Heterogeneous approaches exist in regard to the management of disease-related co-morbidities in potential allogeneic haematopoietic cell transplantation (allo-HCT) candidates with myelofibrosis (MF). The EBMT Chronic Malignancies Working Party launched an electronic survey to evaluate how MF-specific comorbidities are approached and whether they ultimately affect the decision to transplant. A total of 41/63 (65%) Centers, all of whom were experienced in the management of MF allo-HCT, responded. Responses were aggregated and reported in a comparative fashion. Screening for portal hypertension (PH) was routinely performed in 54% centers, never in 12% and guided by clinical manifestations in the remaining. Involvement of hepatologists/gastroenterologists was always/very often considered in patients with signs of PH prior to transplant. Centers reported that radiological evidence of PH did not routinely represent a formal contraindication for allo-HCT in most cases (78%). Of note, most centers (61%) did not perform routine screening for gastroesophageal varices; this was systematically considered or guided by clinical manifestations in only 7% and 32% centers, respectively. Presence of gastroesophageal varices was always (15%) or occasionally (19%) considered a formal contraindication to allo-HCT. A prior history of portal vein thrombosis never (78%) or occasionally (15%) represented a formal contraindication. Three Centers would not proceed to transplant in such cases. Less importance was assigned to non-portal splanchnic vein thrombosis (SVT), with all but one centre proceeding to transplant regardless of prior SVT. This survey highlights a considerable heterogeneity across responding centers in approaching MF-related comorbidities prior to transplant, suggesting that harmonisation guidelines are needed to address these issues in this patient population.

对于骨髓纤维化(MF)潜在异基因造血细胞移植(allo-HCT)候选者的疾病相关合并症,目前存在不同的管理方法。EBMT 慢性恶性肿瘤工作组发起了一项电子调查,以评估如何处理骨髓纤维化特异性合并症,以及这些合并症最终是否会影响移植决定。共有 41/63 个中心(65%)做出了回应,这些中心都在 MF 异体肝移植管理方面经验丰富。我们对回复进行了汇总,并以比较的方式进行了报告。54%的中心常规进行门静脉高压症(PH)筛查,12%的中心从未进行过门静脉高压症筛查,其余的中心则根据临床表现进行筛查。对于在移植前有门静脉高压症状的患者,通常/经常考虑让肝病专家/胃肠病专家参与。各中心报告称,在大多数情况下(78%),PH 的放射学证据并不代表异体肝移植的正式禁忌症。值得注意的是,大多数中心(61%)没有对胃食管静脉曲张进行常规筛查;分别只有7%和32%的中心系统地考虑或根据临床表现进行筛查。胃食管静脉曲张总是(15%)或偶尔(19%)被认为是异体肝细胞移植的正式禁忌症。既往门静脉血栓病史从未(78%)或偶尔(15%)被视为正式禁忌症。有三个中心在这种情况下不会进行移植。对非门静脉脾静脉血栓(SVT)的重视程度较低,除一家中心外,其他所有中心都会进行移植,无论是否曾有 SVT 病史。这项调查凸显了各响应中心在移植前处理 MF 相关合并症方面存在相当大的差异,这表明需要制定统一的指南来解决这类患者的这些问题。
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引用次数: 0
Optimizing CAR-T cell function in solid tumor microenvironment: insights from culture media additives 优化CAR-T细胞在实体肿瘤微环境中的功能:来自培养基添加剂的见解。
IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-12-31 DOI: 10.1016/j.retram.2024.103491
Wenwen Chen, Luxia Xu, Zhigang Guo, Muya Zhou
Cancer remains one of the most pressing health challenges worldwide. Recently, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising approach for treating hematological cancers. However, the translation of CAR-T cell therapy to solid tumors faces formidable obstacles, notably the immunosuppressive tumor microenvironment. Within solid tumors, CAR-T cells encounter a hostile milieu that promotes exhaustion and diminishes their long-term effectiveness against cancer cells. Optimizing the manufacturing process is paramount to ensuring the efficacy of CAR-T cell therapy in solid tumors. A critical aspect of this optimization lies in refining the composition of cell culture media. By supplementing basic culture media with specific additives, researchers aim to improve the behavior and functionality of CAR-T cells, thereby enhancing their therapeutic potential. This review delves into the culture media additives that have been investigated or show promise in modulating CAR-T cell phenotypes and enhancing their anti-tumor efficacy. We explore various types of additives and their mechanisms of action to mitigate exhaustion and augment persistence within the challenging solid tumor microenvironment. By shedding light on the latest advancements in culture media optimization for CAR-T cell therapy, this review aims to provide insights into novel strategies for overcoming the hurdles posed by solid tumors. Ultimately, these insights hold the potential to enhance the effectiveness of CAR-T cell therapy and improve outcomes for cancer patients.
癌症仍然是全世界最紧迫的健康挑战之一。最近,嵌合抗原受体(CAR)-T细胞疗法已成为治疗血液病的一种很有前途的方法。然而,将CAR-T细胞疗法转化为实体肿瘤面临着巨大的障碍,特别是免疫抑制肿瘤微环境。在实体肿瘤中,CAR-T细胞会遇到一个不利的环境,这种环境会促进细胞衰竭,降低它们对抗癌细胞的长期有效性。优化制造工艺对于确保CAR-T细胞治疗实体瘤的疗效至关重要。这种优化的一个关键方面在于改进细胞培养基的组成。通过在基础培养基中添加特定的添加剂,研究人员旨在改善CAR-T细胞的行为和功能,从而增强其治疗潜力。本文综述了已研究或有望调节CAR-T细胞表型和增强其抗肿瘤功效的培养基添加剂。我们探索了各种类型的添加剂及其作用机制,以减轻消耗和增强具有挑战性的实体肿瘤微环境中的持久性。通过揭示CAR-T细胞治疗培养基优化的最新进展,本综述旨在为克服实体瘤带来的障碍提供新的策略。最终,这些见解有可能提高CAR-T细胞治疗的有效性,改善癌症患者的预后。
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Current Research in Translational Medicine
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