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KRT17 serves as an oncogene biomarker of poor survival in patients with hepatocellular carcinoma KRT17是肝细胞癌患者生存率低的癌基因生物标志物
Pub Date : 2023-09-01 DOI: 10.1016/j.bmt.2022.12.002
Jing-Lin Wang , Lu Zhang , Chen-Zhuo Xu , Xue-Qian Qin , Shu-Jun Liu , Bao-Jie Wen , Hao-Zhen Ren

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death from worldwide. Thus, it is imperative to clarify valuable diagnostic and prognostic biomarkers for early-stage HCC. The expression of Keratin 17 (KRT17) has been reported to be associated with certain cancer types previously. However, its role in the development of HCC has not been fully clarified. Here, we assessed the expression of KRT17 in the cancer genome atlas liver hepatocellular carcinoma (TCGA LIHC) database and in 44 pairs of samples collected from patients with HCC. In addition, Kaplan-Meir curves were used to assess the prognostic relevance of KRT17. The essential cancer- and KRT17-related biological processes were defined through gene set enrichment analysis (GSEA). Finally, the functional association between KRT17 expression and tumor cell proliferation/survival was evaluated and the signaling pathways associated with KRT17 expression in HCC were identified. Overall, we found that increased KRT17 levels were associated with lower survival, more aggressive disease, and altered immune cell infiltration in HCC patients. KRT17 may potentially act as a prognostic biomarker in HCC.

肝细胞癌(HCC)是全球癌症死亡的第二大原因。因此,必须阐明早期HCC的有价值的诊断和预后生物标志物。角蛋白17(KRT17)的表达先前已被报道与某些癌症类型相关。然而,它在HCC发展中的作用尚未完全阐明。在此,我们评估了KRT17在癌症基因组图谱肝细胞癌(TCGA LIHC)数据库和从HCC患者收集的44对样本中的表达。此外,Kaplan-Meir曲线用于评估KRT17的预后相关性。通过基因集富集分析(GSEA)确定了癌症和KRT17相关的基本生物学过程。最后,评估了KRT17表达与肿瘤细胞增殖/存活之间的功能相关性,并确定了与HCC中KRT17的表达相关的信号通路。总的来说,我们发现KRT17水平的升高与HCC患者的生存率降低、疾病侵袭性更强和免疫细胞浸润改变有关。KRT17可能作为HCC的预后生物标志物。
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引用次数: 1
Acid-labile chemical bonds-based nanoparticles for endosome escape and intracellular delivery 基于酸不稳定化学键的纳米粒子用于内体逃逸和细胞内递送
Pub Date : 2023-09-01 DOI: 10.1016/j.bmt.2023.01.001
Ruoyu Cheng , Shiqi Wang , Hélder A. Santos

In the last years there has been a booming in the development of biological pharmaceuticals, and various nanoparticle delivery systems have been developed to overcome biological barriers to maximize the therapeutic potentials. Especially, when these drug-loaded nanoparticle systems arrive at the target cells, they must be successfully internalized into the cells, followed by the endosome escape, to release the payload in the cytoplasm. This is crucial so that the payloads are not degraded in the endosome (around pH 6.8–6.0) or lysosome (around pH 4.5). Considering the acid environment of the endosome, several studies have shown the design of different acid-labile nanoparticle delivery systems attempting to achieve endosome escape by, for example, endosomal rupture, membrane destabilization, and membrane fusion. In this mini-review, we summarize current designs in acid-labile chemical bonds for endosome escape of nanosystems. First, we briefly introduce the structural design of acid-labile nanoparticles and their endosomal escape mechanisms. Then, we review recent research work on the topic, highlighting how the nanoparticle designs can be used in endosome escape for different biomedical applications. Finally, we discuss the challenges and future perspectives in this field.

在过去的几年里,生物药物的发展蓬勃发展,各种纳米颗粒递送系统已经被开发出来,以克服生物障碍,最大限度地发挥治疗潜力。特别是,当这些载有药物的纳米颗粒系统到达靶细胞时,它们必须成功地内化到细胞中,然后内体逃逸,以在细胞质中释放有效载荷。这一点至关重要,这样有效载荷就不会在内体(pH 6.8–6.0左右)或溶酶体(pH 4.5左右)中降解。考虑到内体的酸性环境,几项研究表明,设计了不同的酸不稳定纳米颗粒递送系统,试图通过内体破裂、膜不稳定和膜融合等方式实现内体逃逸。在这篇小型综述中,我们总结了目前用于纳米系统内体逃逸的酸不稳定化学键的设计。首先,我们简要介绍了酸不稳定纳米颗粒的结构设计及其内体逃逸机制。然后,我们回顾了最近关于该主题的研究工作,重点介绍了纳米颗粒设计如何用于不同生物医学应用的内体逃逸。最后,我们讨论了这一领域的挑战和未来前景。
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引用次数: 6
Ignored roles of gases in digestive diseases 忽略了气体在消化系统疾病中的作用
Pub Date : 2023-09-01 DOI: 10.1016/j.bmt.2022.11.014
Cheng Zhao , Rui Liu , Yujia Zhou , Ruhua Zheng , Yonghua Shen , Baojie Wen , Bin Zhang , Junyi Che

Complexities of the intestine have brought enormous controversy and discussions to the research on the digestive diseases. The neglected gas environment is crucial in shaping the dynamic intestinal microenvironment. Many gases are involved in the biological activities within the intestinal anaerobic environment, including oxygen, hydrogen, carbon monoxide, ammonia, methane, hydrogen sulfide, carbon dioxide, and nitrogen. These gases participate in the regulation of systemic inflammation and metabolism via different pathways, thereby alleviating or promoting the development of intestinal disease. Meanwhile, the constitution and changes of gases reflect the intestinal environment, which could be utilized to monitor the variation in local metabolism and imply the progress of digestive disorders. However, individual gas has intrinsic functions in maintaining a healthy intestinal microenvironment or causing digestive diseases, and the underlying mechanisms are still unclear. Therefore, exploring the profile of gases in the digestive tract and their extraordinary impact on the intestinal microenvironment will be of great value in understanding the interplay between intestinal health and diseases. By reviewing the research progress of gases in the digestive tract, we anticipate that a better understanding of the roles of gases would promote the research and application transformation in this field as well as the diagnostics and treatment of clinical diseases.

肠道的复杂性给消化系统疾病的研究带来了巨大的争议和讨论。被忽视的气体环境对形成动态肠道微环境至关重要。许多气体参与肠道厌氧环境中的生物活动,包括氧气、氢气、一氧化碳、氨、甲烷、硫化氢、二氧化碳和氮气。这些气体通过不同的途径参与全身炎症和代谢的调节,从而减轻或促进肠道疾病的发展。同时,气体的组成和变化反映了肠道环境,可用于监测局部代谢的变化,提示消化系统疾病的进展。然而,单个气体在维持健康的肠道微环境或引起消化系统疾病方面具有内在功能,其潜在机制尚不清楚。因此,探索消化道中气体的分布及其对肠道微环境的非凡影响,对于理解肠道健康与疾病之间的相互作用具有重要价值。通过回顾消化道中气体的研究进展,我们预计更好地理解气体的作用将促进该领域的研究和应用转型,以及临床疾病的诊断和治疗。
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引用次数: 0
Advance in oral delivery of living material 活体材料口服递送技术的进展
Pub Date : 2023-09-01 DOI: 10.1016/j.bmt.2022.12.003
Hua Liu , Yanmiao Fan , Jie Zhong , Michael Malkoch , Zhengwei Cai , Zhengting Wang

Nowadays, living therapeutics is a promising candidate among various therapies, and oral administration of living therapeutics characterized by universality and safety avail to make the transition from bench to bedside. However, precise delivery and continuous maintenance of cell viability and activity to acquire stable and ideal therapeutic efficacy remain challenging. Living material is the smart integration of the flexibly programmable functionality of biomaterial and the autonomous environmental responsiveness of living elements, heralding a new era of biotherapeutics in addressing human health concerns. Here, our review aims at presenting an overview of the status of the oral delivery of living material from a biological, technical, and practical perspective, describing the clinical significance and potential, the current technological development and dilemma, as well as the prospect.

目前,生活疗法在各种疗法中是一种很有前途的候选者,口服具有普遍性和安全性的生活疗法有助于从台式治疗过渡到床边治疗。然而,精确递送和持续维持细胞活力和活性以获得稳定和理想的治疗效果仍然具有挑战性。生物材料是生物材料灵活可编程功能和生物元素自主环境响应能力的智能集成,预示着生物治疗在解决人类健康问题方面的新时代。在此,我们的综述旨在从生物学、技术和实践的角度概述活体材料口服给药的现状,描述其临床意义和潜力、当前的技术发展和困境以及前景。
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引用次数: 3
Improved efficacy with early tocilizumab in the prophylaxis and treatment of cytokine release syndrome of chimeric antigen receptor T cell (CAR-T) therapy for diffuse large B-cell lymphoma than acute lymphoblastic leukemia 早期使用tocilizumab预防和治疗嵌合抗原受体T细胞(CAR-T)治疗弥漫性大b细胞淋巴瘤的疗效优于急性淋巴细胞白血病
Pub Date : 2023-09-01 DOI: 10.1016/j.bmt.2023.01.002
Chengxin Luan, Haixia Wang, Junjie Zhou, Zhangbiao Long, Xin Chen, Xiaowen Chen, Jing Ni, Zhengqi Huang, Ruixiang Xia, Jian Ge

Background

Tocilizumab is a well-practiced strategy to manage cytokine release syndrome (CRS) after chimeric antigen receptor T cell (CAR-T) therapy. However, varied efficiency in CRS mitigation by tocilizumab has been reported to highlight affecting variables such as tumor types and timing of the administration.

Objective

The objective of this study is to identify different curative effect between diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL) by early use of tocilizumab for prophylaxis and treatment of CRS.

Methods

By retrospectively summarizing our institution's experience with a CAR-T clinical trial targeting CD19, 11 cases were analyzed: 5 DLBCL, and 6 ALL. The two groups were compared with patient characteristics, CRS information and clinical outcomes. 3 patients were pretreated with tocilizumab for prophylaxis and the rest were treated with tocilizumab at CRS diagnosis.

Results

CRS occurred in 81.8% of patients (9/11), grade 3 or higher occurred in 55.6% of the CRS patients (5/9). The two group were similar in patient characteristics, CAR-T and CRS profile. However, tocilizumab produced much better efficacy against CRS in DLBCL group compared with ALL group (80% versus 16.7%, P ​= ​0.08).

Conclusions

Despite the statistical was non-significant, possibly due to small case pool and bias was unavoidable, our analysis suggested that early use of tocilizumab was more effective for DLBCL than ALL in the prophylaxis and treatment of CRS. A treatment algorithm for management of CRS with regard to DLBCL and ALL is proposed, which may extend to other local or systemic malignancies and warrant further investigation.

背景托奇利珠单抗是一种行之有效的治疗嵌合抗原受体T细胞(CAR-T)治疗后细胞因子释放综合征(CRS)的策略。然而,据报道,托西利珠单抗缓解CRS的效率各不相同,突出了肿瘤类型和给药时间等影响因素。目的本研究的目的是通过早期使用托西利珠单抗预防和治疗CRS来确定弥漫性大B细胞淋巴瘤(DLBCL)和急性淋巴细胞白血病(ALL)的不同疗效。方法通过回顾性总结我们机构针对CD19的CAR-T临床试验的经验,分析11例病例:5例DLBCL和6例ALL。比较两组患者的特征、CRS信息和临床结果。3例患者接受托西利珠单抗预处理进行预防,其余患者在CRS诊断时接受托西利珠单抗治疗。结果CRS发生率81.8%(9/11),3级及以上CRS发生率55.6%(5/9)。两组患者的特征、CAR-T和CRS特征相似。然而,与ALL组相比,DLBCL组tocilizumab对CRS的疗效要好得多(80%对16.7%,P​=​0.08)。结论尽管统计数据不显著,可能是由于病例库较小,并且不可避免地存在偏差,但我们的分析表明,在CRS的预防和治疗中,早期使用托西利珠单抗对DLBCL比ALL更有效。提出了一种针对DLBCL和ALL的CRS治疗算法,该算法可以扩展到其他局部或系统性恶性肿瘤,并值得进一步研究。
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引用次数: 0
Bone regeneration and antibacterial properties of calcium-phosphorus coatings induced by gentamicin-loaded polydopamine on magnesium alloys 庆大霉素聚多巴胺诱导镁合金钙磷膜的骨再生及抗菌性能
Pub Date : 2023-07-20 DOI: 10.1016/j.bmt.2023.06.002
Xuecheng Shen , Zhenbao Zhang , Chuxian Cheng , Chang Liu , Nan Ma , Danfang Sun , Dan Li , Chengyue Wang

Improving the corrosion resistance, osteogenic activity, and antimicrobial capacity of the magnesium-based implant is considered the key to promoting their large-scale clinical application. In this study, we reported a novel calcium-phosphorus coating induced by gentamicin (G)-loaded polydopamine for the surface treatment of the magnesium alloy. According to material characterization, immersion tests, and electrochemical analysis, the composite coating has a dense structure and a high crystallinity for greater corrosion resistance. Meanwhile, drug release and antimicrobial experiments demonstrated that the magnesium matrix loaded with gentamicin showed strong inhibition of Escherichia coli and Staphylococcus aureus, and the calcium-phosphorus coating further prolonged the release profile of G, which would contribute to the long-term bactericidal activity of the magnesium implants. In addition, the coating significantly promoted the adhesion, proliferation, and osteogenic differentiation ability of MC3T3-E1. The results of in vivo experiments confirmed that magnesium alloys with composite coatings significantly promoted bone regeneration under infected conditions. This study provides a promising strategy for the development of multifunctional magnesium-based implants with good corrosion resistance, and antibacterial and osteogenic capabilities.

提高镁基植入物的耐腐蚀性、成骨活性和抗菌能力被认为是促进其大规模临床应用的关键。在本研究中,我们报道了一种由庆大霉素(G)负载的聚多巴胺诱导的新型钙磷涂层,用于镁合金的表面处理。根据材料表征、浸渍试验和电化学分析,复合涂层具有致密的结构和高结晶度,具有更大的耐腐蚀性。同时,药物释放和抗菌实验表明,负载庆大霉素的镁基质对大肠杆菌和金黄色葡萄球菌具有较强的抑制作用,钙磷涂层进一步延长了G的释放曲线,这将有助于镁植入物的长期杀菌活性。此外,该涂层显著促进MC3T3-E1的粘附、增殖和成骨分化能力。体内实验结果证实,具有复合涂层的镁合金在感染条件下显著促进骨再生。本研究为开发具有良好耐腐蚀性、抗菌性和成骨能力的多功能镁基植入物提供了一种有前景的策略。
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引用次数: 1
Exploring mitochondrial DNA content as a novel biomarker to improve embryo implantation potential: A review 探索线粒体DNA含量作为一种新的生物标志物,以提高胚胎着床潜力:综述
Pub Date : 2023-07-06 DOI: 10.1016/j.bmt.2023.06.001
Devon Dickson , Tao Tao , Wensheng Qin

According to the society of assisted reproductive technologies (SART), the top fertility clinics in North America have reported overall pregnancy rates of up to 50% in good prognosis patients. Although new techniques in advanced reproductive technologies have begun to emerge in the twenty-first century, including time-lapse monitoring of embryo development, analysis of metabolites in embryo culture media, and the use of artificial intelligence in morphometric embryo grading, currently chromosomal status obtained via pre-implantation genetic testing for aneuploidy (PGT-A) appears to be the most definitive in evaluating embryonic potential. Yet still, in most clinics, approximately 30% of euploid or chromosomally normal embryos fail to achieve a viable pregnancy resulting in stress and anxiety for patients, repeat cycles, and increased cost of treatment. Recent literature suggests that blastocysts with an increased mitochondrial DNA (mtDNA) ratio have greatly reduced implantation potential, however, there exists controversial studies which do not report a relationship. This review summarizes the current literature on utilizing mitochondrial DNA as a possible biomarker for embryo implantation, highlights the reasons for inconsistencies in some studies and suggests possible improvements to the study design of future mtDNA ratio research.

根据辅助生殖技术学会(SART)的数据,北美顶级生育诊所报告称,预后良好的患者的总体妊娠率高达50%。尽管先进生殖技术中的新技术在21世纪开始出现,包括胚胎发育的延时监测、胚胎培养基中代谢物的分析以及人工智能在形态计量胚胎分级中的应用,目前,通过植入前非整倍性基因检测(PGT-A)获得的染色体状态似乎是评估胚胎潜能的最明确的方法。然而,在大多数诊所中,大约30%的整倍体或染色体正常胚胎未能实现可行的妊娠,这给患者带来了压力和焦虑,重复周期,并增加了治疗成本。最近的文献表明,线粒体DNA(mtDNA)比率增加的胚泡极大地降低了植入潜力,然而,也有一些有争议的研究没有报道两者之间的关系。这篇综述总结了目前关于利用线粒体DNA作为胚胎植入的可能生物标志物的文献,强调了一些研究中不一致的原因,并建议对未来线粒体DNA比率研究的研究设计进行可能的改进。
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引用次数: 1
Functional hydrogels for treatment of dental caries 治疗龋齿的功能性水凝胶
Pub Date : 2023-06-15 DOI: 10.1016/j.bmt.2023.05.002
Chuanhui Song , Rui Liu , Bin Kong , Zhuxiao Gu , Guopu Chen

As the most popular teeth problem, dental caries can result in pain, suffering, impaired function, and diminished quality of life among communities, which calls for new strategies to improve the therapeutic effects. With suitable biocompatibility properties, functional hydrogels had developed dramatically in dental caries treatments. In this review, the occurrence and development of dental caries were introduced. Then, the current hydrogels toward dental caries with antibacterial or (and) remineralization properties and hydrogel-related dental pulp tissue engineering were summarized. Finally, the limitation and outlook of the applications of hydrogels on dental caries treatment were prospected. Exploring innovative hydrogel delivery systems will build a solid basis for a brighter future of more friendly, effective and personalized treatment to deal with dental caries.

作为最常见的牙齿问题,龋齿会导致社区的疼痛、痛苦、功能受损和生活质量下降,这就需要采取新的策略来提高治疗效果。由于具有合适的生物相容性,功能性水凝胶在龋齿治疗中得到了显著发展。本文就龋病的发生和发展作一综述。然后,综述了目前具有抗菌或(和)再矿化性能的用于龋齿的水凝胶以及与水凝胶相关的牙髓组织工程。最后,展望了水凝胶在龋病治疗中应用的局限性和前景。探索创新的水凝胶递送系统将为更友好、有效和个性化的龋齿治疗奠定坚实的基础。
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引用次数: 0
Multiscale polymeric fibers for drug delivery and tissue engineering 用于药物输送和组织工程的多尺度聚合物纤维
Pub Date : 2023-06-07 DOI: 10.1016/j.bmt.2023.05.001
Junnan Mu , Danni Luo , Wei Li , Yaping Ding

Owing to their superior capacity for building structures, polymeric fibers with diameters varying from a few nanometers to hundreds of microns have been explored in biomedical applications as drug carriers or tissue engineering scaffolds. Depending on the source materials, fabrication techniques, and post-treatments, both the fiber diameter and surface morphology, as well as mechanical features and the cell-fiber structure interactions can be thoroughly tuned. Although most techniques could produce fibers within a wide range of sizes, each type may have superior advantages in a certain range, which may highly relate to target biomedical fields. Therefore, to properly choose the optimal technique for specific fibers, a comprehensive review of the current fiber-producing techniques is indispensable. In the current review, several main fiber-producing techniques are summarized, compared, and discussed in detail regarding their dominant fiber size ranges, which were classified as nano (<1000 ​nm), micro (1 ​μm−100 μm) and macro (>100 ​μm). The principals, main parameters, and corresponding applications for each technique are reviewed, and the challenges and future perspectives are proposed. We believe this review is highly informative for novice researchers in this field.

由于其卓越的构建结构的能力,直径从几纳米到数百微米不等的聚合物纤维已被探索用于生物医学应用,作为药物载体或组织工程支架。根据源材料、制造技术和后处理,纤维直径和表面形态,以及机械特征和细胞-纤维结构相互作用都可以彻底调整。尽管大多数技术可以生产各种尺寸的纤维,但每种类型的纤维在一定范围内都可能具有优越的优势,这可能与目标生物医学领域高度相关。因此,要正确选择适合特定纤维的最佳工艺,就必须全面回顾当前的纤维生产技术。在目前的综述中,总结、比较和详细讨论了几种主要的纤维生产技术,它们的主要纤维尺寸范围被归类为纳米(<;1000​nm),微米(1​μm−100μm)和宏观(>;100​μm)。综述了每种技术的原理、主要参数和相应的应用,并提出了挑战和未来展望。我们相信这篇综述对该领域的新手研究人员来说是非常有信息的。
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引用次数: 2
Tailoring micro/nano-materials with special wettability for biomedical devices 为生物医学设备定制具有特殊润湿性的微/纳米材料
Pub Date : 2023-06-01 DOI: 10.1016/j.bmt.2022.11.005
Shuangshuang Miao , Xinyue Cao , Minhui Lu , Xiangdong Liu

Wettability, as a fundamental property of interface materials, is becoming increasingly prominent in frontier research areas, such as water harvesting, microfluidics, biomedicine, sensors, decontamination, wearables, and micro-electromechanical systems. Taking advantage of biological paradigm inspirations and manufacturing technology advancements, diverse wettability materials with precisely customized micro/nano-structures have been developed. As a result of these achievements, wettability materials have significant technical ramifications in sectors spanning from academics to industry, agriculture, and biomedical engineering. Practical applications of wettability-customized materials in medical device domains have drawn significant scientific interest in recent decades due to the increased emphasis on healthcare. In this review, recent advances of wettability-customized micro/nano-materials for biomedical devices are presented. After briefly introducing the natural wettable/non-wettable phenomena, the fabrication strategies and novel processing techniques are discussed. The study emphasizes the application progress of biomedical devices with customized wettability. The future challenges and opportunities of wettability-customized micro/nano-materials are also provided.

润湿性作为界面材料的一种基本性质,在集水、微流体、生物医学、传感器、去污、可穿戴设备和微机电系统等前沿研究领域越来越突出。利用生物学范式的灵感和制造技术的进步,开发出了具有精确定制的微/纳米结构的各种润湿性材料。由于这些成就,润湿性材料在从学术到工业、农业和生物医学工程的各个领域都产生了重大的技术影响。近几十年来,由于对医疗保健的日益重视,润湿性定制材料在医疗器械领域的实际应用引起了极大的科学兴趣。本文综述了用于生物医学器件的润湿性定制微/纳米材料的最新进展。在简要介绍了自然可湿/不可湿现象后,讨论了制备策略和新的加工技术。该研究强调了具有定制润湿性的生物医学器件的应用进展。还提供了润湿性定制微/纳米材料未来的挑战和机遇。
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引用次数: 10
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Biomedical Technology
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