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The Role of Gasdermin-D-Mediated Pyroptosis in Organ Injury and Its Therapeutic Implications. Gasdermin-D介导的Pyroposis在器官损伤中的作用及其治疗意义。
IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-31 DOI: 10.1080/15476278.2023.2177484
Joud Mulla, Rohan Katti, Melanie J Scott

Gasdermin-D (GSDMD) belongs to the Gasdermin family (GSDM), which are pore-forming effector proteins that facilitate inflammatory cell death, also known as pyroptosis. This type of programmed cell death is dependent on inflammatory caspase activation, which cleaves gasdermin-D (GSDMD) to form membrane pores and initiates the release of pro-inflammatory cytokines. Pyroptosis plays an important role in achieving immune regulation and homeostasis within various organ systems. The role of GSDMD in pyroptosis has been extensively studied in recent years. In this review, we summarize the role of GSDMD in cellular and organ injury mediated by pyroptosis. We will also provide an outlook on GSDMD therapeutic targets in various organ systems.

Gasdermin-D(GSDMD)属于Gasdermin家族(GSDM),是一种促进炎症细胞死亡的成孔效应蛋白,也称为Pyroposis。这种类型的程序性细胞死亡依赖于炎症性半胱天冬酶的激活,后者切割gasdermin-D(GSDMD)形成膜孔,并启动促炎细胞因子的释放。Pyroptosis在实现各种器官系统内的免疫调节和稳态方面发挥着重要作用。近年来,GSDMD在pyroptosis中的作用已被广泛研究。在这篇综述中,我们总结了GSDMD在pyroptosis介导的细胞和器官损伤中的作用。我们还将展望GSDMD在各种器官系统中的治疗靶点。
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引用次数: 0
Human Hepatocellular response in Cholestatic Liver Diseases. 胆固醇性肝病中的人肝细胞反应。
IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-31 DOI: 10.1080/15476278.2023.2247576
Kimberly Ortiz, Zeliha Cetin, Yiyue Sun, Zhiping Hu, Takeshi Kurihara, Edgar N Tafaleng, Rodrigo M Florentino, Alina Ostrowska, Alejandro Soto-Gutierrez, Lanuza A P Faccioli

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the most common types of cholestatic liver disease (CLD), result in enterohepatic obstruction, bile acid accumulation, and hepatotoxicity. The mechanisms by which hepatocytes respond to and cope with CLD remain largely unexplored. This study includes the characterization of hepatocytes isolated from explanted livers of patients with PBC and PSC. We examined the expression of hepatocyte-specific genes, intracellular bile acid (BA) levels, and oxidative stress in primary-human-hepatocytes (PHHs) isolated from explanted livers of patients with PBC and PSC and compared them with control normal human hepatocytes. Our findings provide valuable initial insights into the hepatocellular response to cholestasis in CLD and help support the use of PHHs as an experimental tool for these diseases.

原发性胆汁性胆管炎(PBC)和原发性硬化性胆管管炎(PSC)是最常见的胆汁淤积性肝病(CLD)类型,可导致肠肝梗阻、胆汁酸积聚和肝毒性。肝细胞对CLD反应和应对CLD的机制在很大程度上尚未探索。本研究包括从PBC和PSC患者的移植肝脏中分离的肝细胞的特征。我们检测了从PBC和PSC患者的移植肝脏中分离的原代人肝细胞(PHH)中肝细胞特异性基因的表达、细胞内胆汁酸(BA)水平和氧化应激,并将其与对照正常人肝细胞进行比较。我们的发现为CLD中肝细胞对胆汁淤积的反应提供了有价值的初步见解,并有助于支持PHHs作为治疗这些疾病的实验工具。
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引用次数: 0
Focusing on Hippo Pathway in Stem Cells of Oral Origin, Enamel Formation and Periodontium Regeneration. 重点研究口腔起源干细胞、牙釉质形成和牙周组织再生中的Hippo通路。
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-12-31 DOI: 10.1080/15476278.2022.2082236
Tianyi Wang, Kehan Li, Hanghang Liu, En Luo

Hippo pathway is a cellular regulatory pathway composed of core molecules such as MST1/2, LATS1/2, SAV1, MOB1A/B and downstream YAP/TAZ. Fully involved in regulating cell proliferation, differentiation, migration and apoptosis, the Hippo pathway is critical in regulating stem cells of oral origin, for instance, DPSCs and PDLSCs, enamel formation and periodontium regeneration. Here, we summarized the Hippo pathway involved in these progresses and concluded crosstalks of the Hippo pathway with BCL-2, ERK1/2, ROCK, TGF-β/BMP and Wnt/β-catenin pathways, hoping to provide foundation for further clinical therapy.

Hippo通路是由MST1/2、LATS1/2、SAV1、MOB1A/B及下游的YAP/TAZ等核心分子组成的细胞调控通路。Hippo通路全面参与细胞增殖、分化、迁移和凋亡的调控,在口腔来源的干细胞(如DPSCs和PDLSCs)、牙釉质形成和牙周组织再生中起着关键作用。在此,我们总结了参与这些进展的Hippo通路,并总结了Hippo通路与BCL-2、ERK1/2、ROCK、TGF-β/BMP和Wnt/β-catenin通路的串串,以期为进一步的临床治疗提供依据。
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引用次数: 1
Applications of Transcriptomics in the Research of Antibody-Mediated Rejection in Kidney Transplantation: Progress and Perspectives. 转录组学在肾移植抗体介导排斥反应研究中的应用:进展与展望。
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-12-31 DOI: 10.1080/15476278.2022.2131357
Hsuan Yeh

Antibody-mediated rejection (ABMR) is the major cause of chronic allograft dysfunction and loss in kidney transplantation. The immunological mechanisms of ABMR that have been featured in the latest studies indicate a highly complex interplay between various immune and nonimmune cell types. Clinical diagnostic standards have long been criticized for being arbitrary and the lack of accuracy. Transcriptomic approaches, including microarray and RNA sequencing of allograft biopsies, enable the identification of differential gene expression and the continuous improvement of diagnostics. Given that conventional bulk transcriptomic approaches only reflect the average gene expression but not the status at the single-cell level, thereby ignoring the heterogeneity of the transcriptome across individual cells, single-cell RNA sequencing is rising as a powerful tool to provide a high-resolution transcriptome map of immune cells, which allows the elucidation of the pathogenesis and may facilitate the development of novel strategies for clinical treatment of ABMR.

抗体介导的排斥反应(ABMR)是肾移植中慢性同种异体移植物功能障碍和丧失的主要原因。最新研究表明,ABMR的免疫学机制在各种免疫和非免疫细胞类型之间具有高度复杂的相互作用。长期以来,临床诊断标准一直被批评为武断和缺乏准确性。转录组学方法,包括异体移植物活检的微阵列和RNA测序,使鉴别差异基因表达和不断改进诊断成为可能。鉴于传统的大量转录组方法只反映了平均基因表达,而不是单细胞水平的状态,从而忽略了单个细胞转录组的异质性,单细胞RNA测序作为提供免疫细胞高分辨率转录组图的有力工具正在崛起,这使得阐明发病机制成为可能,并可能促进ABMR临床治疗新策略的发展。
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引用次数: 0
A Systematic Approach of the Intrauterine Morphogenesis of the Human Palpebral Apparatus. 人眼睑器官宫内形态发生的系统研究。
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-12-31 DOI: 10.1080/15476278.2022.2066453
Octavian Munteanu, Florin-Mihail Filipoiu, Monica Mihaela Cirstoiu, Roxana Elena Bohiltea, Tiberiu Augustin Georgescu, Adrian Dumitru, Andra-Ioana Băloiu, Mihai-Alin Publik, Ioan-Andrei Petrescu

The human eyelid embodies a vast diversity of functions. Acting as a protective shield for the ocular apparatus and as a light regulator in the sight process, eyelids stand a fascinating - yet omitted - role in facial aesthetics, serving as a racial trait by which humankind succeeded to manifest heterogeneity as a species. These assumptions are precisely forecasted right from in-utero life through intricate processes of growth and cell differentiation. In the Department of Anatomy of "Carol Davila" University of Medicine and Pharmacy, we performed morphological assessments on 41 embryos and fetuses with gestational ages ranging from 6 to 29 weeks. This study aims to illustrate the morphogenesis of eyelids in human embryos and fetuses and highlight macroscopic features which could potentially have significant clinical implications in ophthalmic pathology.

人类的眼睑具有多种多样的功能。作为眼部器官的保护罩和视觉过程中的光调节器,眼睑在面部美学中扮演着一个迷人的——但被忽略的——角色,作为一种种族特征,人类成功地表现出作为一个物种的异质性。这些假设是通过复杂的生长和细胞分化过程在子宫内精确预测出来的。在“Carol Davila”医药大学解剖学系,我们对41例胎龄6 ~ 29周的胚胎和胎儿进行了形态学评估。本研究旨在阐明人类胚胎和胎儿眼睑的形态发生,并强调可能在眼科病理学中具有重要临床意义的宏观特征。
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引用次数: 0
Hepatocyte Differentiation from iPSCs or MSCs in Decellularized Liver Scaffold: Cell–ECM Adhesion, Spatial Distribution, and Hepatocyte Maturation Profile 去细胞化肝支架中多能干细胞或间充质干细胞的肝细胞分化:细胞- ecm粘附、空间分布和肝细胞成熟谱
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-04-17 DOI: 10.1080/15476278.2022.2061263
R. Antarianto, Adrian Pragiwaksana, Wahyunia Likhayati Septiana, N. F. Mazfufah, A. Mahmood
ABSTRACT Mesenchymal stem cells (MSC) and induced pluripotent stem cells (iPSC) have been reported to be able to differentiate to hepatocyte in vitro with varying degree of hepatocyte maturation. A simple method to decellularize liver scaffold has been established by the Department of Histology, Faculty of Medicine, Universitas Indonesia, in SCTE IMERI lab.15 This study aims to evaluate hepatocyte differentiation from iPSCs compared to MSCs derived in our decellularized liver scaffold. The research stages started with iPSC culture, decellularization, seeding cell culture into the scaffold, and differentiation into hepatocytes for 21 days. Hepatocyte differentiation from iPSCs and MSCs in the scaffolds was characterized using hematoxylin–eosin, Masson Trichrome, and immunohistochemistry staining to determine the fraction of the differentiation area. RNA samples were isolated on days 7 and 21. Expression of albumin, CYP450, and CK-19 genes were analyzed using the qRT-PCR method. Electron microscopy images were obtained by SEM. Immunofluorescence examination was done using HNF4-α and CEBPA markers. The results of this study in hepatocyte-differentiated iPSCs compared with hepatocyte-differentiated MSCs in decellularized liver scaffold showed lower adhesion capacity, single-cell-formation and adhered less abundant, decreased trends of albumin, and lower CYP450 expression. Several factors contribute to this result: lower initial seeding number, which causes only a few iPSCs to attach to certain parts of decellularized liver scaffold, and manual syringe injection for recellularization, which abruptly and unevenly creates pattern of single-cell-formation by hepatocyte-differentiated iPSC in the scaffold. Hepatocyte-differentiated MSCs have the advantage of higher adhesion capacity to collagen fiber decellularized liver scaffold. This leads to positive result: increase trends of albumin and higher CYP450 expression. Hepatocyte maturation is shown by diminishing CK-19, which is more prominent in hepatocyte-differentiated iPSCs in decellularized liver scaffold. Confirmation of mature hepatocyte-differentiated iPSCs in decellularized liver scaffold maturation is positive for HNF4-a and CEBPA. The conclusion of this study is hepatocyte-differentiated iPSCs in decellularized liver scaffold is mature with lower cell–ECM adhesion, spatial cell distribution, albumin, and CYP450 expression than hepatocyte-differentiated MSCs in decellularized liver scaffold.
摘要间充质干细胞(MSC)和诱导多能干细胞(iPSC)已被报道能够在不同程度的肝细胞成熟的情况下在体外分化为肝细胞。印度尼西亚大学医学院组织学系在SCTE IMERI实验室建立了一种简单的肝支架脱细胞方法。15本研究旨在评估iPSC与脱细胞肝支架中衍生的MSC的肝细胞分化。研究阶段从iPSC培养、脱细胞、将细胞培养物植入支架并分化为肝细胞开始,持续21天。使用苏木精-伊红、Masson三色染色和免疫组织化学染色来表征支架中iPSC和MSCs的肝细胞分化,以确定分化区域的比例。在第7天和第21天分离RNA样品。使用qRT-PCR方法分析白蛋白、CYP450和CK-19基因的表达。用扫描电镜获得电镜图像,用HNF4-α和CEBPA标记进行免疫荧光检测。与脱细胞肝支架中的肝细胞分化的MSCs相比,本研究在肝细胞分化型iPSC中的结果显示出较低的粘附能力、单细胞形成和粘附量较低、白蛋白趋势降低以及CYP450表达较低。有几个因素促成了这一结果:较低的初始接种数量,这导致只有少数iPSC附着在脱细胞肝支架的某些部分,以及手动注射器注射用于再细胞化,这突然而不均匀地在支架中由肝细胞分化的iPSC形成单细胞模式。肝细胞分化的MSCs对胶原纤维脱细胞肝支架具有较高的粘附能力。这导致了积极的结果:白蛋白的增加趋势和CYP450的更高表达。肝细胞成熟表现为CK-19减少,这在脱细胞肝支架中肝细胞分化的iPSC中更为突出。HNF4-a和CEBPA证实在脱细胞肝支架成熟中成熟的肝细胞分化的iPSC是阳性的。本研究的结论是,与脱细胞肝支架中的肝细胞分化的MSCs相比,脱细胞肝框架中的肝细胞核分化的iPSC是成熟的,具有更低的细胞-ECM粘附力、空间细胞分布、白蛋白和CYP450表达。
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引用次数: 8
Variations in Aspects of Neural Precursor Cell Neurogenesis in a Human Model of HSV-1 Infection 1型单纯疱疹病毒感染人模型中神经前体细胞神经发生方面的变化
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-04-06 DOI: 10.1080/15476278.2022.2055354
Wenxiao Zheng, Emily M. Benner, D. Bloom, Vaishali Muralidaran, Jill K. Caldwell, Anuya Prabhudesai, P. Piazza, J. Wood, P. Kinchington, V. Nimgaonkar, L. D’Aiuto
ABSTRACT Encephalitis, the most significant of the central nervous system (CNS) diseases caused by Herpes simplex virus 1 (HSV-1), may have long-term sequelae in survivors treated with acyclovir, the cause of which is unclear. HSV-1 exhibits a tropism toward neurogenic niches in CNS enriched with neural precursor cells (NPCs), which play a pivotal role in neurogenesis. NPCs are susceptible to HSV-1. There is a paucity of information regarding the influence of HSV-1 on neurogenesis in humans. We investigated HSV-1 infection of NPCs from two individuals. Our results show (i) HSV-1 impairs, to different extents, the proliferation, self-renewing, and, to an even greater extent, migration of NPCs from these two subjects; (ii) The protective effect of the gold-standard antiherpetic drug acyclovir (ACV) varies with viral dose and is incomplete. It is also subject to differences in terms of efficacy of the NPCs derived from these two individuals. These results suggest that the effects of HSV-1 may have on aspects of NPC neurogenesis may vary among individuals, even in the presence of acyclovir, and this may contribute to the heterogeneity of cognitive sequelae across encephalitis survivors. Further analysis of NPC cell lines from a larger number of individuals is warranted.
脑炎是由单纯疱疹病毒1型(HSV-1)引起的最重要的中枢神经系统(CNS)疾病,在接受阿昔洛韦治疗的幸存者中可能有长期后遗症,其原因尚不清楚。HSV-1在神经发生中起关键作用的神经前体细胞(neural precursor cells, npc)富集的中枢神经系统中表现出向神经发生龛的倾向。npc易感染HSV-1。关于1型单纯疱疹病毒对人类神经发生的影响的信息缺乏。我们调查了2例npc的HSV-1感染情况。结果表明:(1)HSV-1在不同程度上抑制了这两种个体的npc的增殖、自我更新,并在更大程度上抑制了它们的迁移;(二)金标准抗疱疹药物阿昔洛韦(ACV)的保护作用因病毒剂量而异,而且是不完全的。这也取决于这两个个体衍生的npc的功效差异。这些结果表明,即使在无环鸟苷存在的情况下,HSV-1对NPC神经发生的影响可能在个体之间有所不同,这可能导致脑炎幸存者认知后遗症的异质性。进一步分析来自更多个体的鼻咽癌细胞系是有必要的。
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引用次数: 2
Connection of ES Cell-derived Collecting Ducts and Ureter-like Structures to Host Kidneys in Culture. 胚胎干细胞衍生的收集管和输尿管样结构与宿主肾脏的连接。
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-10-02 Epub Date: 2021-09-27 DOI: 10.1080/15476278.2021.1936785
May Sallam, Jamie Davies

Work toward renal generation generally aims either to introduce suspensions of stem cells into kidneys in the hope that they will rebuild damaged tissue, or to construct complete new kidneys from stem cells with the aim of transplanting the engineered organs. In principle, there might be a third approach; to engineer renal tissue 'modules' in vitro and to use them to replace sections of damaged host kidney. This approach would require the urine collecting system or ureter of the new tissues to connect to those of the host. In this report, we demonstrate a method that allows collecting duct trees or ureters, engineered from ES cells, to connect to the collecting duct system or ureter, respectively, of fetal kidneys in culture.

肾脏生成的研究通常旨在将干细胞悬浮液引入肾脏,希望它们能重建受损组织,或者用干细胞构建完整的新肾脏,目的是移植工程器官。原则上,可能存在第三种方法;在体外设计肾脏组织“模块”,并用它们来替代受损的宿主肾脏。这种方法需要新组织的尿液收集系统或输尿管与宿主的尿液收集系统或输尿管相连。在本报告中,我们展示了一种方法,可以将胚胎干细胞工程的收集管树或输尿管分别连接到培养的胎儿肾脏的收集管系统或输尿管。
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引用次数: 1
Human Hepatocytes Isolated from Explanted Livers: A Powerful Tool to Understand End-stage Liver Disease and Drug Screening. 从外植肝脏中分离的人肝细胞:了解终末期肝病和药物筛选的有力工具。
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-10-02 DOI: 10.1080/15476278.2021.1992216
Lanuza A P Faccioli, Zehra N Kocas-Kilicarslan, Ricardo Diaz-Aragon, Takashi Motomura, Sriram Amirneni, Michelle R Malizio, Michael C Coard, Carla Frau, Nils Haep, Rodrigo M Florentino, Alina Ostrowska

The use of primary human hepatocytes has been hampered by limited availability of adequate numbers of fresh and viable cells due to the ongoing shortage of liver donors. Thus, there is no surplus of healthy organs from which freshly isolated cells can be prepared when needed. However, primary hepatocytes can be successfully isolated from explanted liver specimens obtained from patients receiving orthotopic liver transplantation for decompensated liver cirrhosis or for metabolic liver disease without end-stage liver disease and are a valuable resource for the pharmaceutical industry research. This review focuses on the isolation, characterization and cryopreservation of hepatocytes derived from therapeutically resected livers with various hepatic diseases.

由于肝脏供体持续短缺,新鲜和活细胞数量有限,阻碍了原代人肝细胞的使用。因此,没有多余的健康器官可以在需要时从中制备新鲜分离的细胞。然而,原代肝细胞可以成功地从接受原位肝移植的失代偿肝硬化或代谢性肝病无终末期肝病患者的外植肝标本中分离出来,是制药行业研究的宝贵资源。本文综述了各种肝脏疾病治疗性切除肝脏中肝细胞的分离、表征和冷冻保存。
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引用次数: 1
Potential of Autologous Progenitor Cells and Decellularized Porcine Artery Matrix in Construction of Tissue-engineered Vascular Grafts. 自体祖细胞和脱细胞猪动脉基质在构建组织工程血管移植物中的潜力
IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-10-02 Epub Date: 2021-08-18 DOI: 10.1080/15476278.2021.1963603
Jieh-Neng Wang, Chung-Dann Kan, Shao-Hsien Lin, Ko-Chi Chang, Stephanie Tsao, Tak-Wah Wong

To develop a tissue-engineered vascular graft, we used pericardial effusion-derived progenitor cells (PEPCs) collected from drained fluid after open-heart surgery in children with congenital heart diseases to repopulate a decellularized porcine pulmonary artery. The PEPCs were compared with human fibroblasts (HS68) and human umbilical vein endothelial cells (HUVECs) in cell growth and migration. They were cultured with the matrices via an inner approach (intima), lateral approach (media), and outer approach (adventitia). PEPCs grew and migrated better than the other two cells 14 days after seeding in the decellularized vessel. In immunofluorescence assays, PEPCs expressed CD90 and CD105 indicating a vascular differentiation. PEPCs grew in a decellularized porcine pulmonary artery matrix may have the potential for producing tissue-engineered vascular grafts.

为了开发一种组织工程血管移植物,我们利用从先天性心脏病患儿开胸手术后排出的液体中收集的心包积液衍生祖细胞(PEPCs)重新填充脱细胞猪肺动脉。在细胞生长和迁移方面,PEPCs 与人成纤维细胞(HS68)和人脐静脉内皮细胞(HUVECs)进行了比较。它们通过内侧(内膜)、外侧(中膜)和外侧(外膜)与基质一起培养。在脱细胞血管中播种 14 天后,PEPCs 的生长和迁移优于其他两种细胞。在免疫荧光检测中,PEPCs 表达了 CD90 和 CD105,表明其已向血管分化。在脱细胞猪肺动脉基质中生长的 PEPCs 可能具有制造组织工程血管移植物的潜力。
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引用次数: 0
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Organogenesis
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