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Extracellular vesicles from 3D cultured dermal papilla cells improve wound healing via Krüppel-like factor 4/vascular endothelial growth factor A -driven angiogenesis. 来自3D培养的真皮乳头细胞的细胞外小泡通过Krüppel样因子4/血管内皮生长因子A驱动的血管生成改善伤口愈合。
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-10-30 eCollection Date: 2023-01-01 DOI: 10.1093/burnst/tkad034
Yunwei Wang, Kuo Shen, Yulin Sun, Peng Cao, Jia Zhang, Wanfu Zhang, Yang Liu, Hao Zhang, Yang Chen, Shaohui Li, Chaolei Xu, Chao Han, Yating Qiao, Qingyi Zhang, Bin Wang, Liang Luo, Yunshu Yang, Hao Guan

Background: Non-healing wounds are an intractable problem of major clinical relevance. Evidence has shown that dermal papilla cells (DPCs) may regulate the wound-healing process by secreting extracellular vesicles (EVs). However, low isolation efficiency and restricted cell viability hinder the applications of DPC-EVs in wound healing. In this study, we aimed to develop novel 3D-DPC spheroids (tdDPCs) based on self-feeder 3D culture and to evaluate the roles of tdDPC-EVs in stimulating angiogenesis and skin wound healing.

Methods: To address the current limitations of DPC-EVs, we previously developed a self-feeder 3D culture method to construct tdDPCs. DPCs and tdDPCs were identified using immunofluorescence staining and flow cytometry. Subsequently, we extracted EVs from the cells and compared the effects of DPC-EVs and tdDPC-EVs on human umbilical vein endothelial cells (HUVECs) in vitro using immunofluorescence staining, a scratch-wound assay and a Transwell assay. We simultaneously established a murine model of full-thickness skin injury and evaluated the effects of DPC-EVs and tdDPC-EVs on wound-healing efficiency in vivo using laser Doppler, as well as hematoxylin and eosin, Masson, CD31 and α-SMA staining. To elucidate the underlying mechanism, we conducted RNA sequencing (RNA-seq) of tdDPC-EV- and phosphate-buffered saline-treated HUVECs. To validate the RNA-seq data, we constructed knockdown and overexpression vectors of Krüppel-like factor 4 (KLF4). Western blotting, a scratch-wound assay, a Transwell assay and a tubule-formation test were performed to detect the protein expression, cell migration and lumen-formation ability of KLF4 and vascular endothelial growth factor A (VEGFA) in HUVECs incubated with tdDPC-EVs after KLF4 knockdown or overexpression. Dual-luciferase reporter gene assays were conducted to verify the activation effect of KLF4 on VEGFA.

Results: We successfully cultured tdDPCs and extracted EVs from DPCs and tdDPCs. The tdDPC-EVs significantly promoted the proliferation, lumen formation and migration of HUVECs. Unlike DPC-EVs, tdDPC-EVs exhibited significant advantages in terms of promoting angiogenesis, accelerating wound healing and enhancing wound-healing efficiency both in vitro and in vivo. Bioinformatics analysis and further functional experiments verified that the tdDPC-EV-regulated KLF4/VEGFA axis is pivotal in accelerating wound healing.

Conclusions: 3D cultivation can be utilized as an innovative optimization strategy to effectively develop DPC-derived EVs for the treatment of skin wounds. tdDPC-EVs significantly enhance wound healing via KLF4/VEGFA-driven angiogenesis.

背景:不愈合的伤口是一个棘手的问题,具有重要的临床意义。有证据表明,毛乳头细胞(DPCs)可能通过分泌细胞外小泡(EVs)来调节伤口愈合过程。然而,低的分离效率和有限的细胞活力阻碍了DPC-EVs在伤口愈合中的应用。在本研究中,我们旨在开发基于自饲养3D培养的新型3D-DPC球体(tdDPCs),并评估tdDPC-EVs在刺激血管生成和皮肤伤口愈合中的作用。方法:为了解决目前DPC-EVs的局限性,我们之前开发了一种自饲养三维培养方法来构建TDDPC。用免疫荧光染色和流式细胞术鉴定DPCs和tdDPCs。随后,我们从细胞中提取EVs,并使用免疫荧光染色、划痕试验和Transwell试验在体外比较DPC-EVs和tdDPC-EVs对人脐静脉内皮细胞(HUVECs)的影响。我们同时建立了全层皮肤损伤的小鼠模型,并使用激光多普勒以及苏木精和伊红、Masson、CD31和α-SMA染色评估了DPC-EVs和tdDPC-EVs对体内伤口愈合效率的影响。为了阐明潜在的机制,我们对tdDPC EV和磷酸盐缓冲盐水处理的HUVECs进行了RNA测序(RNA-seq)。为了验证RNA-seq数据,我们构建了Krüppel样因子4(KLF4)的敲除和过表达载体。进行蛋白质印迹、划痕试验、Transwell试验和小管形成试验,以检测KLF4和血管内皮生长因子a(VEGFA)在敲低或过表达后与tdDPC-EVs孵育的HUVECs中的蛋白质表达、细胞迁移和管腔形成能力。进行双荧光素酶报告基因测定以验证KLF4对VEGFA的激活作用。结果:我们成功地培养了tdDPCs,并从DPCs和tdDPCs中提取了EVs。tdDPC-EVs显著促进HUVECs的增殖、管腔形成和迁移。与DPC-EVs不同,tdDPC-EVs在体外和体内都表现出促进血管生成、加速伤口愈合和提高伤口愈合效率的显著优势。生物信息学分析和进一步的功能实验证实,tdDPC-EV调节的KLF4/VEGFA轴在加速伤口愈合方面至关重要。结论:3D培养可作为一种创新的优化策略,有效开发用于治疗皮肤伤口的DPC衍生EVs。tdDPC-EVs通过KLF4/VEGFA驱动的血管生成显著增强伤口愈合。
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引用次数: 0
In vitro comparison of human plasma-based and self-assembled tissue-engineered skin substitutes: two different manufacturing processes for the treatment of deep and difficult to heal injuries. 基于人血浆和自组装组织工程皮肤替代品的体外比较:两种不同的制造工艺,用于治疗深度和难以愈合的损伤。
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-10-30 eCollection Date: 2023-01-01 DOI: 10.1093/burnst/tkad043
Álvaro Sierra-Sánchez, Brice Magne, Etienne Savard, Christian Martel, Karel Ferland, Martin A Barbier, Anabelle Demers, Danielle Larouche, Salvador Arias-Santiago, Lucie Germain

Background: The aim of this in vitro study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes (hbTESSs) designed for the treatment of severely burned patients. These are the scaffold-free self-assembled skin substitute (SASS) and the human plasma-based skin substitute (HPSS).

Methods: Fibroblasts and keratinocytes from three humans were extracted from skin biopsies (N = 3) and cells from the same donor were used to produce both hbTESS models. For SASS manufacture, keratinocytes were seeded over three self-assembled dermal sheets comprising fibroblasts and the extracellular matrix they produced (n = 12), while for HPSS production, keratinocytes were cultured over hydrogels composed of fibroblasts embedded in either plasma as unique biomaterial (Fibrin), plasma combined with hyaluronic acid (Fibrin-HA) or plasma combined with collagen (Fibrin-Col) (n/biomaterial = 9). The production time was 46-55 days for SASSs and 32-39 days for HPSSs. Substitutes were characterized by histology, mechanical testing, PrestoBlue™-assay, immunofluorescence (Ki67, Keratin (K) 10, K15, K19, Loricrin, type IV collagen) and Western blot (type I and IV collagens).

Results: The SASSs were more resistant to tensile forces (p-value < 0.01) but less elastic (p-value < 0.001) compared to HPSSs. A higher number of proliferative Ki67+ cells were found in SASSs although their metabolic activity was lower. After epidermal differentiation, no significant difference was observed in the expression of K10, K15, K19 and Loricrin. Overall, the production of type I and type IV collagens and the adhesive strength of the dermal-epidermal junction was higher in SASSs.

Conclusions: This study demonstrates, for the first time, that both hbTESS models present similar in vitro biological characteristics. However, mechanical properties differ and future in vivo experiments will aim to compare their wound healing potential.

背景:这项体外研究的目的是比较用于治疗严重烧伤患者的两种并排的人类双层组织工程皮肤替代品(hbTESS)模型。这些是无支架的自组装皮肤替代品(SASS)和基于人血浆的皮肤替代物(HPSS) = 3) 并且使用来自同一供体的细胞来产生两种hbTESS模型。对于SASS的制造,将角质形成细胞接种在包括成纤维细胞和它们产生的细胞外基质(n = 12) ,而对于HPSS的生产,角质形成细胞是在水凝胶上培养的,水凝胶由成纤维细胞组成,成纤维细胞包埋在血浆中作为独特的生物材料(纤维蛋白),血浆与透明质酸结合(纤维蛋白HA)或血浆与胶原结合(纤维素Col)(n/生物材料 = 9) 。SASS的生产时间为46-55天,HPSS的生产时间则为32-39天。通过组织学、机械测试、PrestoBlue对替代品进行了表征™-免疫荧光(Ki67,Keratin(K)10,K15,K19,Loricrin,IV型胶原)和Western印迹(I型和IV型胶原蛋白) p值 + 在SASS中发现了细胞,尽管它们的代谢活性较低。表皮分化后,K10、K15、K19和Loricrin的表达没有显著差异。总的来说,SASS中I型和IV型胶原的产生以及真皮-表皮连接处的粘附强度更高。结论:本研究首次证明,两种hbTESS模型都具有相似的体外生物学特性。然而,机械性能各不相同,未来的体内实验将旨在比较它们的伤口愈合潜力。
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引用次数: 0
Tailored biomedical materials for wound healing. 为伤口愈合量身定制的生物医学材料。
IF 6.3 1区 医学 Q1 DERMATOLOGY Pub Date : 2023-10-26 eCollection Date: 2023-01-01 DOI: 10.1093/burnst/tkad040
Wenhui Liu, Lihua Zu, Shanzheng Wang, Jingyao Li, Xiaoyuan Fei, Meng Geng, Chunlei Zhu, Hui Shi

Wound healing is a long-term, multi-stage biological process that mainly includes haemostatic, inflammatory, proliferative and tissue remodelling phases. Controlling infection and inflammation and promoting tissue regeneration can contribute well to wound healing. Smart biomaterials offer significant advantages in wound healing because of their ability to control wound healing in time and space. Understanding how biomaterials are designed for different stages of wound healing will facilitate future personalized material tailoring for different wounds, making them beneficial for wound therapy. This review summarizes the design approaches of biomaterials in the field of anti-inflammatory, antimicrobial and tissue regeneration, highlights the advanced precise control achieved by biomaterials in different stages of wound healing and outlines the clinical and practical applications of biomaterials in wound healing.

伤口愈合是一个长期、多阶段的生物学过程,主要包括止血、炎症、增殖和组织重塑阶段。控制感染和炎症以及促进组织再生可以很好地促进伤口愈合。智能生物材料在伤口愈合方面具有显著优势,因为它们能够在时间和空间上控制伤口愈合。了解生物材料是如何为伤口愈合的不同阶段设计的,将有助于未来为不同伤口定制个性化材料,使其对伤口治疗有益。本文综述了生物材料在抗炎、抗菌和组织再生领域的设计方法,重点介绍了生物材料对伤口愈合不同阶段实现的先进精确控制,并概述了生物材料的临床和实际应用。
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引用次数: 0
P-MSC-derived extracellular vesicles facilitate diabetic wound healing via miR-145-5p/ CDKN1A-mediated functional improvements of high glucose-induced senescent fibroblasts. P-MSC衍生的细胞外小泡通过miR-145-5p/CDKN1A介导的高糖诱导的衰老成纤维细胞的功能改善促进糖尿病伤口愈合。
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-10-18 eCollection Date: 2023-01-01 DOI: 10.1093/burnst/tkad010
Jianlong Su, Qian Wei, Kui Ma, Yaxi Wang, Wenzhi Hu, Hao Meng, Qiankun Li, Yuehou Zhang, Wenhua Zhang, Haihong Li, Xiaobing Fu, Cuiping Zhang

Background: Persistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts (HDFs), partially leading to delayed skin wound healing. Extracellular vesicles (EVs) containing multiple pro-healing microRNAs (miRNAs) have been shown to exert therapeutic effects on diabetic wound healing. The present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells (P-MSC-EVs) on diabetic wound healing and high glucose (HG)-induced senescent fibroblasts and to explore the underlying mechanisms.

Methods: P-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice, to observe the beneficial effects on wound healing in vivo by measuring wound closure rates and histological analysis. Next, a series of assays were conducted to evaluate the effects of low (2.28 x 1010 particles/ml) and high (4.56 x 1010 particles/ml) concentrations of P-MSC-EVs on the senescence, proliferation, migration, and apoptosis of HG-induced senescent HDFs in vitro. Then, miRNA microarrays and real-time quantitative PCR (RT-qPCR) were carried out to detect the differentially expressed miRNAs in HDFs after EVs treatment. Specific RNA inhibitors, miRNA mimics, and small interfering RNA (siRNA) were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent HDFs.

Results: Local injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths, with better-organized collagen deposition and decreased p16INK4a expression. In vitro, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent fibroblasts. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)/protein kinase B (Akt) signaling pathway. Furthermore, local application of miR-145-5p agomir mimicked the effects of P-MSC-EVs on wound healing.

Conclusions: These results suggest that P-MSC-EVs accelerate diabetic wound healing by improving the function of senescent fibroblasts through the transfer of miR-145-5p, which targets cyclin-dependent kinase inhibitor 1A to activate the Erk/Akt signaling pathway. P-MSC-EVs are promising therapeutic candidates for diabetic wound treatment.

背景:糖尿病患者持续的高血糖会导致人类真皮成纤维细胞(HDFs)功能异常,部分导致皮肤伤口愈合延迟。含有多种促进愈合的微小RNA(miRNA)的细胞外小泡(EVs)已被证明对糖尿病伤口愈合具有治疗作用。本研究旨在观察来自胎盘间充质干细胞(P-MSC-EVs)的EVs对糖尿病伤口愈合和高糖(HG)诱导的衰老成纤维细胞的影响,并探讨其潜在机制。方法:采用差速超速离心法分离P-MSC-EV,并将其局部注射到糖尿病小鼠全层皮肤伤口中,通过测量伤口闭合率和组织学分析,观察其对体内伤口愈合的有益作用。接下来,进行了一系列测定,以评估低(2.28 x 1010颗粒/ml)和高(4.56 x 1010颗粒g/ml)浓度的P-MSC-EVs对体外HG诱导的衰老HDFs的衰老、增殖、迁移和凋亡的影响。然后,进行miRNA微阵列和实时定量PCR(RT-qPCR)来检测EVs治疗后HDFs中差异表达的miRNA。使用特异性RNA抑制剂、miRNA模拟物和小干扰RNA(siRNA)来评估候选miRNA及其靶基因在P-MSC-EV诱导的HG诱导的衰老HDF功能改善中的作用,具有更好组织的胶原沉积和降低的p16INK4a表达。在体外,P-MSC-EVs以剂量依赖的方式增强HG诱导的衰老成纤维细胞的抗衰老、增殖、迁移和抗凋亡能力。发现MiR-145-5p在P-MSC-EV中高度富集。MiR-145-5p抑制剂有效地减弱了P-MSC-EV诱导的衰老成纤维细胞的功能改善。MiR-145-5p模拟物通过抑制细胞周期蛋白依赖性激酶抑制剂1A的表达和激活细胞外信号调节激酶(Erk)/蛋白激酶B(Akt)信号通路,模拟P-MSC-EVs对成纤维细胞功能改善的影响。此外,miR-145-5p agomir的局部应用模拟了P-MSC-EVs对伤口愈合的影响。结论:这些结果表明,P-MSC-EVs通过转移miR-145-5p改善衰老成纤维细胞的功能,从而加速糖尿病伤口愈合,miR-145-5p靶向细胞周期蛋白依赖性激酶抑制剂1A,激活Erk/Akt信号通路。P-MSC-EV是糖尿病伤口治疗的有前景的候选治疗药物。
{"title":"P-MSC-derived extracellular vesicles facilitate diabetic wound healing via miR-145-5p/ CDKN1A-mediated functional improvements of high glucose-induced senescent fibroblasts.","authors":"Jianlong Su,&nbsp;Qian Wei,&nbsp;Kui Ma,&nbsp;Yaxi Wang,&nbsp;Wenzhi Hu,&nbsp;Hao Meng,&nbsp;Qiankun Li,&nbsp;Yuehou Zhang,&nbsp;Wenhua Zhang,&nbsp;Haihong Li,&nbsp;Xiaobing Fu,&nbsp;Cuiping Zhang","doi":"10.1093/burnst/tkad010","DOIUrl":"https://doi.org/10.1093/burnst/tkad010","url":null,"abstract":"<p><strong>Background: </strong>Persistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts (HDFs), partially leading to delayed skin wound healing. Extracellular vesicles (EVs) containing multiple pro-healing microRNAs (miRNAs) have been shown to exert therapeutic effects on diabetic wound healing. The present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells (P-MSC-EVs) on diabetic wound healing and high glucose (HG)-induced senescent fibroblasts and to explore the underlying mechanisms.</p><p><strong>Methods: </strong>P-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice, to observe the beneficial effects on wound healing <i>in vivo</i> by measuring wound closure rates and histological analysis. Next, a series of assays were conducted to evaluate the effects of low (2.28 x 10<sup>10</sup> particles/ml) and high (4.56 x 10<sup>10</sup> particles/ml) concentrations of P-MSC-EVs on the senescence, proliferation, migration, and apoptosis of HG-induced senescent HDFs <i>in vitro</i>. Then, miRNA microarrays and real-time quantitative PCR (RT-qPCR) were carried out to detect the differentially expressed miRNAs in HDFs after EVs treatment. Specific RNA inhibitors, miRNA mimics, and small interfering RNA (siRNA) were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent HDFs.</p><p><strong>Results: </strong>Local injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths, with better-organized collagen deposition and decreased p16INK4a expression. <i>In vitro</i>, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent fibroblasts. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)/protein kinase B (Akt) signaling pathway. Furthermore, local application of miR-145-5p agomir mimicked the effects of P-MSC-EVs on wound healing.</p><p><strong>Conclusions: </strong>These results suggest that P-MSC-EVs accelerate diabetic wound healing by improving the function of senescent fibroblasts through the transfer of miR-145-5p, which targets cyclin-dependent kinase inhibitor 1A to activate the Erk/Akt signaling pathway. P-MSC-EVs are promising therapeutic candidates for diabetic wound treatment.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Actin polymerization inhibition by targeting ARPC2 affects intestinal stem cell homeostasis. 通过靶向ARPC2抑制肌动蛋白聚合影响肠道干细胞稳态。
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-10-16 eCollection Date: 2023-01-01 DOI: 10.1093/burnst/tkad038
Ruzhen Zhang, Sheng Chen, Zhifan Yang, Ning Zhang, Kenan Guo, Keyi Lv, Zimo Zhou, Meijiao Gao, Xiancheng Hu, Yongping Su, Jianming He, Fengchao Wang

Background: The rapid turnover of the intestinal epithelium is driven by the proliferation and differentiation of intestinal stem cells (ISCs). The dynamics of the F-actin cytoskeleton are critical for maintaining intercellular force and the signal transduction network. However, it remains unclear how direct interference with actin polymerization impacts ISC homeostasis. This study aims to reveal the regulatory effects of the F-actin cytoskeleton on the homeostasis of intestinal epithelium, as well as the potential risks of benproperine (BPP) as an anti-tumor drug.

Methods: Phalloidin fluorescence staining was utilized to test F-actin polymerization. Flow cytometry and IHC staining were employed to discriminate different types of intestinal epithelial cells. Cell proliferation was assessed through bromo-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. The proliferation and differentiation of intestinal stem cells were replicated in vitro through organoid culture. Epithelial migration was evaluated through BrdU pulse labeling and chasing in mice.

Results: The F-actin content was observed to significantly increase as crypt cells migrated into the villus region. Additionally, actin polymerization in secretory cells, especially in Paneth cells (PCs), was much higher than that in neighboring ISCs. Treatment with the newly identified actin-related protein 2/3 complex subunit 2 (ARPC2) inhibitor BPP led to a dose-dependent increase or inhibition of intestinal organoid growth in vitro and crypt cell proliferation in vivo. Compared with the vehicle group, BPP treatment decreased the expression of Lgr5 ISC feature genes in vivo and in organoid culture. Meanwhile, PC differentiation derived from ISCs and progenitors was decreased by inhibition of F-actin polymerization. Mechanistically, BPP-induced actin polymerization inhibition may activate the Yes1-associated transcriptional regulator pathway, which affects ISC proliferation and differentiation. Accordingly, BPP treatment affected intestinal epithelial cell migration in a dose-dependent manner.

Conclusion: Our findings indicate that the regulation of cytoskeleton reorganization can affect ISC homeostasis. In addition, inhibiting ARPC2 with the Food and Drug Administration-approved drug BPP represents a novel approach to influencing the turnover of intestinal epithelial cells.

背景:肠上皮的快速周转是由肠干细胞(ISCs)的增殖和分化驱动的。F-肌动蛋白细胞骨架的动力学对于维持细胞间作用力和信号转导网络至关重要。然而,目前尚不清楚肌动蛋白聚合的直接干扰如何影响ISC稳态。本研究旨在揭示F-肌动蛋白细胞骨架对肠上皮稳态的调节作用,以及苯丙胺(BPP)作为抗肿瘤药物的潜在风险。方法:用Phalloidin荧光染色法检测F-肌动蛋白的聚合作用。采用流式细胞术和IHC染色对不同类型的肠上皮细胞进行鉴别。通过溴脱氧尿苷(BrdU)和5-乙炔基-2'-脱氧尿苷掺入测定来评估细胞增殖。通过类器官培养在体外复制肠道干细胞的增殖和分化。通过BrdU脉冲标记和小鼠追逐来评估上皮迁移。结果:随着隐窝细胞向绒毛区迁移,F-肌动蛋白含量显著增加。此外,分泌细胞中的肌动蛋白聚合,特别是Paneth细胞(PC),远高于邻近ISC。用新鉴定的肌动蛋白相关蛋白2/3复合物亚基2(ARPC2)抑制剂BPP治疗导致体外肠道类器官生长和体内隐窝细胞增殖的剂量依赖性增加或抑制。与载体组相比,BPP处理降低了Lgr5-ISC特征基因在体内和类器官培养中的表达。同时,来自ISCs和祖细胞的PC分化通过抑制F-肌动蛋白聚合而降低。从机制上讲,BPP诱导的肌动蛋白聚合抑制可能激活Yes1相关的转录调节通路,从而影响ISC的增殖和分化。因此,BPP治疗以剂量依赖的方式影响肠上皮细胞的迁移。结论:细胞骨架重组的调控可以影响ISC的稳态。此外,用美国食品药品监督管理局批准的药物BPP抑制ARPC2代表了一种影响肠上皮细胞更新的新方法。
{"title":"Actin polymerization inhibition by targeting ARPC2 affects intestinal stem cell homeostasis.","authors":"Ruzhen Zhang,&nbsp;Sheng Chen,&nbsp;Zhifan Yang,&nbsp;Ning Zhang,&nbsp;Kenan Guo,&nbsp;Keyi Lv,&nbsp;Zimo Zhou,&nbsp;Meijiao Gao,&nbsp;Xiancheng Hu,&nbsp;Yongping Su,&nbsp;Jianming He,&nbsp;Fengchao Wang","doi":"10.1093/burnst/tkad038","DOIUrl":"10.1093/burnst/tkad038","url":null,"abstract":"<p><strong>Background: </strong>The rapid turnover of the intestinal epithelium is driven by the proliferation and differentiation of intestinal stem cells (ISCs). The dynamics of the F-actin cytoskeleton are critical for maintaining intercellular force and the signal transduction network. However, it remains unclear how direct interference with actin polymerization impacts ISC homeostasis. This study aims to reveal the regulatory effects of the F-actin cytoskeleton on the homeostasis of intestinal epithelium, as well as the potential risks of benproperine (BPP) as an anti-tumor drug.</p><p><strong>Methods: </strong>Phalloidin fluorescence staining was utilized to test F-actin polymerization. Flow cytometry and IHC staining were employed to discriminate different types of intestinal epithelial cells. Cell proliferation was assessed through bromo-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. The proliferation and differentiation of intestinal stem cells were replicated <i>in vitro</i> through organoid culture. Epithelial migration was evaluated through BrdU pulse labeling and chasing in mice.</p><p><strong>Results: </strong>The F-actin content was observed to significantly increase as crypt cells migrated into the villus region. Additionally, actin polymerization in secretory cells, especially in Paneth cells (PCs), was much higher than that in neighboring ISCs. Treatment with the newly identified actin-related protein 2/3 complex subunit 2 (ARPC2) inhibitor BPP led to a dose-dependent increase or inhibition of intestinal organoid growth <i>in vitro</i> and crypt cell proliferation <i>in vivo</i>. Compared with the vehicle group, BPP treatment decreased the expression of Lgr5 ISC feature genes <i>in vivo</i> and in organoid culture. Meanwhile, PC differentiation derived from ISCs and progenitors was decreased by inhibition of F-actin polymerization. Mechanistically, BPP-induced actin polymerization inhibition may activate the Yes1-associated transcriptional regulator pathway, which affects ISC proliferation and differentiation. Accordingly, BPP treatment affected intestinal epithelial cell migration in a dose-dependent manner.</p><p><strong>Conclusion: </strong>Our findings indicate that the regulation of cytoskeleton reorganization can affect ISC homeostasis. In addition, inhibiting ARPC2 with the Food and Drug Administration-approved drug BPP represents a novel approach to influencing the turnover of intestinal epithelial cells.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms. 一种可光活化的苯基硼酸功能化纳米组件,用于对抗多重耐药革兰氏阴性菌及其生物膜。
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-10-16 eCollection Date: 2023-01-01 DOI: 10.1093/burnst/tkad041
Xiaoqing Zhou, Lanlan Dong, Baohua Zhao, Guangyun Hu, Can Huang, Tengfei Liu, Yifei Lu, Mengxue Zheng, Yanlan Yu, Zengjun Yang, Shaowen Cheng, Yan Xiong, Gaoxing Luo, Wei Qian, Rui Yin

Background: Multidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover, the formation of biofilms makes these bacteria difficult to control. Therefore, developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N, N'-di-sec-butyl-N, N'- dinitroso-1,4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.

Methods: The characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay, plate counting method and live/dead staining in vitro. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo. A cell counting kit-8 assay, Calcein/PI cytotoxicity assay, hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo.

Results: Herein, we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT), photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser, IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation, which further reacted with ROS to generate ONOO-, leading to the enhancement of bactericidal efficacy. Furthermore, NO and ONOO- could disrupt the cell membrane, which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study, IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections, relief of inflammation, promotion of re-epithelization and collagen deposition, and regulation of angiogenesis during wound healing. Moreover, IRNB exhibited excellent biocompatibility, both in vitro and in vivo.

Conclusions: The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.

背景:多重耐药(MDR)革兰氏阴性菌相关传染病已导致公共卫生负担和死亡率的增加。此外,生物膜的形成使这些细菌难以控制。因此,迫切需要开发新的干预措施来对抗耐多药革兰氏阴性菌及其生物膜相关感染。本研究的目的是开发一种基于IR-780和N,N'-二-叔丁基-N,N'--二硝基-1,4-苯二胺(BNN6)的多功能纳米组装体(IRNB),对革兰氏阴性菌引起的感染伤口和皮下脓肿具有协同作用。方法:研究IRNB的特性及其对细菌的靶向性。通过结晶紫染色法、平板计数法和体外活/死染色法证明了IRNB对革兰氏阴性菌及其生物膜的杀菌效果。在体内皮下脓肿和皮肤感染伤口模型上检测IRNB的抗菌效果。采用细胞计数试剂盒-8法、Calcein/PI细胞毒性法、溶血法和静脉注射法检测IRNB的体内外生物相容性。结果:在此,我们成功开发了一种基于IR-780和BNN6的多功能纳米组件IRNB,用于808nm激光触发的协同光热治疗(PTT)、光动力治疗(PDT)和一氧化氮(NO)效应。这种纳米组装体可以通过共价偶联效应在耐多药革兰氏阴性菌及其生物膜的感染部位特异性积累。在用808nm激光照射时,IRNB被激活并产生活性氧(ROS)和高温。局部高温可诱导NO生成,NO与ROS进一步反应生成ONOO-,从而增强杀菌效果。此外,NO和ONOO-可以破坏细胞膜,将细菌转化为极其敏感的状态,并进一步增强光热效应。在这项研究中,IRNB对革兰氏阴性菌引起的感染伤口和皮下脓肿显示出优越的光热光动力化学(NO)协同治疗效果。这导致了对相关感染的有效控制、炎症的缓解、再上皮化和胶原沉积的促进以及伤口愈合过程中血管生成的调节。此外,IRNB在体外和体内均表现出良好的生物相容性。结论:目前的研究表明,IRNB可以被认为是治疗耐多药革兰氏阴性菌及其生物膜引起的感染的一种有前途的替代方案。
{"title":"A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms.","authors":"Xiaoqing Zhou,&nbsp;Lanlan Dong,&nbsp;Baohua Zhao,&nbsp;Guangyun Hu,&nbsp;Can Huang,&nbsp;Tengfei Liu,&nbsp;Yifei Lu,&nbsp;Mengxue Zheng,&nbsp;Yanlan Yu,&nbsp;Zengjun Yang,&nbsp;Shaowen Cheng,&nbsp;Yan Xiong,&nbsp;Gaoxing Luo,&nbsp;Wei Qian,&nbsp;Rui Yin","doi":"10.1093/burnst/tkad041","DOIUrl":"10.1093/burnst/tkad041","url":null,"abstract":"<p><strong>Background: </strong>Multidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover, the formation of biofilms makes these bacteria difficult to control. Therefore, developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N, N'-di-sec-butyl-N, N'- dinitroso-1,4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.</p><p><strong>Methods: </strong>The characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay, plate counting method and live/dead staining <i>in vitro</i>. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model <i>in vivo</i>. A cell counting kit-8 assay, Calcein/PI cytotoxicity assay, hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Results: </strong>Herein, we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT), photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser, IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation, which further reacted with ROS to generate ONOO<sup>-</sup>, leading to the enhancement of bactericidal efficacy. Furthermore, NO and ONOO<sup>-</sup> could disrupt the cell membrane, which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study, IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections, relief of inflammation, promotion of re-epithelization and collagen deposition, and regulation of angiogenesis during wound healing. Moreover, IRNB exhibited excellent biocompatibility, both <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Conclusions: </strong>The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/7f/tkad041.PMC10578387.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mathematical modeling of variants of thoracolumbar junction transpedicular fixation after resection of Th12 vertebra under compressive load 压缩载荷下Th12椎体切除后胸腰椎节段经椎弓根固定变异体的数学建模
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-09-04 DOI: 10.22141/1608-1706.2.24.2023.940
O. Nekhlopochyn, V. Verbov, I. Cheshuk, M. Karpinsky, O. Yaresko
Background. The area of the thoracolumbar junction is characterized by a significant load that dictates increased requirements to stabilization, which should not only provide a reliable and rigid fixation, but also ensure the maximum uniform distribution of the load on all elements of both the metal structure and the bone tissue to exclude the failure of fixation in the long run. Purpose of the study is to investigate the influence of the transpedicular screw length and the presence of crosslinks on the load distribution during surgical resection of one vertebra from the thoracolumbar junction under the influence of axial compressive load. Materials and methods. We analyzed mathematical finite-element model of the part of thoracolumbar spine (Th9-L5), where the Th12 vertebra was removed and replaced by an interbody implant with additional fixation by a transpedicular system. Four variants of transpedicular fixation were modeled using short and long screws, as well as with and without two crosslinks. The stress-strain state of the models was studied under the influence of a vertical compressive distributed load of 350 N. Results. When using short screws and in the absence of crosslinks, the maximum stresses in the Th10, Th11, L1, and L2 vertebrae are 7.2, 5.3, 4.2, and 14.3 MPa, respectively, when using long screws without crosslinks — 6.5, 4.6, 3.8 and 13.5 MPa. The model with short screws and crosslinks shows 7.1, 4.4, 3.9 and 14.0 MPa, while the application of long screws with crosslinks is 6.3, 4.5, 3.5 and 13.2 MPa, respectively. Conclusions. With a compressive load, the use of long screws allows to reduce the level of stress in the bone elements of the models, the use of crosslinks provides greater rigidity to the posterior support of the transpedicular structure, which leads to an increase in stress on the fixing screws but allows to reduce the level of stress in the bone tissue.
背景。胸腰椎连接处的特点是负荷较大,对稳定的要求增加,这不仅要提供可靠和刚性的固定,而且要确保金属结构和骨组织的所有元素上负荷的最大均匀分布,以排除长期固定失败。本研究的目的是探讨在轴向压缩载荷的影响下,椎弓根螺钉长度和交联的存在对手术切除胸腰椎交界处一节椎体的载荷分布的影响。材料和方法。我们分析了部分胸腰椎(Th9-L5)的数学有限元模型,其中Th12椎体被切除并用椎间植入物取代,并通过椎弓根系统进行额外固定。采用短螺钉和长螺钉,以及带和不带两个交联,模拟了四种不同的经椎弓根固定。研究了在350 n垂直分布压荷载作用下模型的应力-应变状态。当使用短螺钉和无交联时,Th10、Th11、L1和L2椎体的最大应力分别为7.2、5.3、4.2和14.3 MPa,而使用无交联的长螺钉时为6.5、4.6、3.8和13.5 MPa。短螺杆和交联的模型分别为7.1、4.4、3.9和14.0 MPa,长螺杆和交联的模型分别为6.3、4.5、3.5和13.2 MPa。结论。在压缩载荷下,使用长螺钉可以降低模型骨单元的应力水平,使用交联可以为经椎弓根结构的后部支持提供更大的刚度,这导致固定螺钉上的应力增加,但可以降低骨组织中的应力水平。
{"title":"Mathematical modeling of variants of thoracolumbar junction transpedicular fixation after resection of Th12 vertebra under compressive load","authors":"O. Nekhlopochyn, V. Verbov, I. Cheshuk, M. Karpinsky, O. Yaresko","doi":"10.22141/1608-1706.2.24.2023.940","DOIUrl":"https://doi.org/10.22141/1608-1706.2.24.2023.940","url":null,"abstract":"Background. The area of the thoracolumbar junction is characterized by a significant load that dictates increased requirements to stabilization, which should not only provide a reliable and rigid fixation, but also ensure the maximum uniform distribution of the load on all elements of both the metal structure and the bone tissue to exclude the failure of fixation in the long run. Purpose of the study is to investigate the influence of the transpedicular screw length and the presence of crosslinks on the load distribution during surgical resection of one vertebra from the thoracolumbar junction under the influence of axial compressive load. Materials and methods. We analyzed mathematical finite-element model of the part of thoracolumbar spine (Th9-L5), where the Th12 vertebra was removed and replaced by an interbody implant with additional fixation by a transpedicular system. Four variants of transpedicular fixation were modeled using short and long screws, as well as with and without two crosslinks. The stress-strain state of the models was studied under the influence of a vertical compressive distributed load of 350 N. Results. When using short screws and in the absence of crosslinks, the maximum stresses in the Th10, Th11, L1, and L2 vertebrae are 7.2, 5.3, 4.2, and 14.3 MPa, respectively, when using long screws without crosslinks — 6.5, 4.6, 3.8 and 13.5 MPa. The model with short screws and crosslinks shows 7.1, 4.4, 3.9 and 14.0 MPa, while the application of long screws with crosslinks is 6.3, 4.5, 3.5 and 13.2 MPa, respectively. Conclusions. With a compressive load, the use of long screws allows to reduce the level of stress in the bone elements of the models, the use of crosslinks provides greater rigidity to the posterior support of the transpedicular structure, which leads to an increase in stress on the fixing screws but allows to reduce the level of stress in the bone tissue.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73433131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Study of load in the sacroiliac joint during dynamic simulation of movements in the lumbar spine on skeletal muscle models after posterior bisegmental fusion 后半节段融合后骨骼肌模型动态模拟腰椎运动时骶髂关节负荷的研究
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-09-04 DOI: 10.22141/1608-1706.2.24.2023.944
O. Barkov, R.V. Malyk, O. Karpinska
Background. Complications are the main concern of patients and surgeons when considering spine surgery. One of the risk factors for complications in the thoracic and lumbar spinal segments, as well as segments adjacent to those with fusion, is changes in sagittal spinal-pelvic balance. Objective: to determine the effect of muscle changes that occur during surgical access for posterior bisegmental LIV-SI fusion on the load of the iliac crest surface in the sacroiliac joint. Materials and methods. Dynamic motion simulation modeling was performed using OpenSim software with the use of additional programs to calculate loading forces. The complete model of the human musculoskeletal system was taken as a basis. To compare the load force, four models were created: 1 — basic, all spinal motion segments are fully functional, 2 — fixation without changing the anatomical curves of the spine, 3 — fixation in the position of hyperlordosis; 4 — fixation with reproduction of hyperlordosis. For models 2–4, changes in the muscles were made that correspond to the effects of surgical posterior access to the lumbar spine for posterior instrumented fusion LIV-SI. The load on the area of interest was measured as the value of the projection of the force vector depending on the angle of torso inclination as a percentage of body weight. Results. Muscle strength and function were the same for all types of instrumental spinal fusion, and trauma during access was not taken into account. In model 1 (normal) with the upright position, the projection of the load force falls on the center of gravity of the vertebra. When tilted, the load force in the sagittal direction acts exclusively on the anterior ilium with a slight shift of 10 % forward. In normosthenic and hyperlordotic fixation, there is a shift in the projection of the load force on the posterior iliac crest in the upright position and its displacement to the center with the tilt. The displacement of the load center with the upright position in normosthenic fixation is associated with the exclusion of some extensor muscles from the calculation of fibers, which reduces their total strength and leads to sagittal imbalance with an increase in lordosis. Hypolordotic fixation (model 4) slightly shifts the projection of the load force in the upright position (by 3 %) and approaches the normal values of model 1 when tilted. Regarding vertical loads, for all models with muscle integrity impairment (models 2, 3, 4), the load in the upright position is greatly increased — on average by 60 % compared to the norm, with a decrease in body weight by 40–45 % when tilted. Conclusions. It has been proved that the load force on the surface of the iliac crest in the sacroiliac joint depends on the angle of instrumental fusion performed. The greatest changes are observed with the displacement of the load center during upright standing in the sagittal direction. In normosthenic and hyperlordotic fixation with decreased back muscle strength
背景。在考虑脊柱手术时,并发症是患者和外科医生主要关心的问题。胸腰椎节段以及融合后相邻节段并发症的危险因素之一是矢状面脊柱-骨盆平衡的改变。目的:探讨后半节段LIV-SI融合手术入路中发生的肌肉变化对骶髂关节髂嵴面负荷的影响。材料和方法。采用OpenSim软件进行动态运动仿真建模,并利用附加程序计算加载力。以完整的人体肌肉骨骼系统模型为基础。为了比较载荷力,我们建立了四种模型:1 -基本模型,所有脊柱运动节段功能齐全,2 -固定不改变脊柱解剖曲线,3 -固定在脊柱前凸部位;4 .固定伴前凸过度再生产。对于模型2-4,肌肉的变化与手术后路进入腰椎进行后路内固定LIV-SI融合的效果相对应。在感兴趣的区域上的负载被测量为力向量的投影值,这取决于躯干倾斜的角度占体重的百分比。结果。所有类型的器械脊柱融合术的肌肉力量和功能是相同的,并且不考虑入路过程中的创伤。在模型1(法向)中,竖直位置,载荷力的投影落在椎体的重心上。当倾斜时,矢状方向的载荷力仅作用于前髂骨,向前轻微移动10%。在正常张力和前凸过度固定中,直立位置时髂后嵴上的负荷力投射发生变化,并随着倾斜向中心移位。在正张力固定中,负荷中心与直立位置的位移与一些伸肌在纤维计算中被排除有关,这降低了它们的总强度,导致矢状面不平衡,并增加了前凸。低倾角固定(模型4)使直立位置的载荷力投射略微偏移(偏移3%),倾斜位置时接近模型1的正常值。关于垂直负荷,对于所有肌肉完整性受损的模型(模型2、3、4),直立位置的负荷大大增加——与正常位置相比平均增加60%,倾斜位置时体重减少40 - 45%。结论。经证实,骶髂关节内髂骨表面的载荷与器械融合术的角度有关。在矢状方向直立站立时,载荷中心的位移变化最大。在背肌力下降的正常张力和高前凸固定中,有一个负荷转移到髂嵴后部。在低椎弓背固定中,载荷中心保持靠近中心位置。负荷在垂直方向上的分布主要受背部肌肉力量减少的影响,背部肌肉力量的减少使负荷增加了60%。
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引用次数: 0
Diagnosis, treatment and monitoring of patients with primary malignant tumors of the bones of the pelvis and lower extremities: promising technologies 骨盆和下肢原发性恶性肿瘤患者的诊断、治疗和监测:有前途的技术
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-09-04 DOI: 10.22141/1608-1706.2.24.2023.945
O. Drobotun
Background. Diagnosis and treatment of patients with malignant bone tumors requires continuous improvement of existing methods of diagnosis and treatment. Purpose: to improve the treatment results in patients with tumors of the femur and pelvis through the application of medical imaging technologies, 3D modeling and 3D printing of personalized models of bones and tumors, arthroplasty and bioactive ceramics. Materials and methods. Examination, treatment and monitoring of 28 patients with malignant tumors of the bones of the pelvis, lower extremities and examination of 16 apparently healthy people were performed. Computed tomography (CT) and magnetic resonance imaging (MRI), 3D modeling, biochemical markers of bone metabolism, arthroplasty, biomine were applied. Results. The technology of creating a 3D model of bones affected by malignant tumors has been developed based on the results of MRI, CT and 3D printing. Preoperative planning and training on 3D models reliably reduced intraoperative blood loss, duration of surgery, time of complete recovery of the extremity function, the risk of postoperative complications and, accordingly, increased the duration of the first recurrence-free period. The use of bone resorption and osteosynthesis markers allows to control the osseointegration of endoprosthesis and biomine, to diagnose recurrence/metastasis timely. Conclusions. The application of CT + MRI + 3D modeling + training on 3D models + tumor removal + arthroplasty + biomine algorithm provided functional results after 12 months: excellent — in 57.35 %, good — in 29.41 % of cases. Postoperative complications were observed only in 12.2 % of patients, local recurrences — in 7.3 %.
背景。恶性骨肿瘤患者的诊治需要不断改进现有的诊疗方法。目的:通过医学影像技术、骨肿瘤个性化模型的3D建模和3D打印、关节成形术和生物活性陶瓷的应用,提高股骨、骨盆肿瘤患者的治疗效果。材料和方法。对28例骨盆、下肢骨恶性肿瘤患者进行了检查、治疗和监测,并对16例表面健康的人进行了检查。应用计算机断层扫描(CT)和磁共振成像(MRI)、三维建模、骨代谢生化标志物、关节成形术、生物胺。结果。基于MRI、CT和3D打印的结果,已经开发出了创建受恶性肿瘤影响的骨骼3D模型的技术。术前规划和3D模型训练可靠地减少了术中出血量、手术时间、四肢功能完全恢复时间和术后并发症的风险,从而增加了第一次无复发期的时间。使用骨吸收和骨合成标志物可以控制假体和生物胺的骨整合,及时诊断复发/转移。结论。应用CT + MRI + 3D建模+ 3D模型训练+肿瘤切除+关节置换术+生物胺算法12个月后功能效果:优57.35%,良29.41%。术后并发症发生率仅为12.2%,局部复发发生率为7.3%。
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引用次数: 0
Study of changes in the balance of the pelvic girdle muscles in patients with dysplastic coxarthrosis after arthroplasty 关节成形术后发育不良髋关节患者骨盆带肌平衡变化的研究
IF 5.3 1区 医学 Q1 Medicine Pub Date : 2023-09-04 DOI: 10.22141/1608-1706.2.24.2023.943
O. D. Karpinskaya, M.Y. Karpinsky, O. Tyazhelov, V. Klymovytskyy, L.D. Goncharova, D. Yurchenko
Background. Dysplastic coxarthrosis is a special medical and social problem in the treatment of adult patients, often leading to disability, limiting the human’s ability to self-care. Arthroplasty for dysplastic coxarthrosis is only a certain stage in the restoration of the patient’s musculoskeletal function. Considering the large number of unsatisfactory results of arthroplasty in dysplastic coxarthrosis, a very important factor is the construction of a rehabilitation prognosis — the estimated probability of achieving the intended goals of rehabilitation or realization of rehabilitation potential, taking into account disease features and the patient’s capabilities. Objective: to determine the significant parameters of the dysplastic hip joint whose change affects the deficit of lower limb muscle strength after arthroplasty and the prospects for rehabilitation potential. Materials and methods. An X-ray examination of 23 dysplastic hip joints was performed. The following radiometric parameters were measured: acetabular depth; floor thickness; acetabular depth index; abductor moment arm; gravity moment arm; height and lateralization of the center of rotation of the femoral head relative to the center of the acetabulum rotation. To objectify the balance of muscle forces required to maintain pelvic balance when standing on one leg, a mathematical model was used created by the authors, which reflects the pelvis with the femur and the action vectors of the muscles of two groups: abductors and adductors of the hip. Results. Using the model of horizontal balance of the pelvis, the level of muscle strength deficit was calculated in patients before and after arthroplasty. It was found that in some of them the muscle strength deficit remained. With a linear regression model, an equation was created to determine the muscle strength deficit. According to the statistical analysis, no difference was found between the results of the regression equation and the mathematical model (p >> 0.05). The regression analysis has shown that the most significant factors for the result are the neck shaft angle, floor thickness, and head height. To determine the limits of radiometric parameters that affect the outcome of arthroplasty, patients were divided into 4 groups according to the level of calculated muscle strength deficit: group I — deficit of more than 20 %, group II — deficit of less than 20 %, group III — surplus of 20 % and group IV — surplus of more than 20 %. In general, patients improve their muscle strength, but the initial deficit greatly affects the outcome after arthroplasty. For patients in group I, pre- and postoperative rehabilitation is necessary to achieve a positive result. In group II, the main direction of rehabilitation is to increase muscle strength. For patients of groups III and IV, general rehabilitation measures can be used. Conclusions. The most important parameter that affects muscle strength after arthroplasty is the patient’s muscle streng
背景。关节发育不良是成人患者治疗中一个特殊的医学和社会问题,往往导致残疾,限制了人的自我照顾能力。关节成形术治疗发育不良的肩关节只是恢复患者肌肉骨骼功能的一个阶段。考虑到关节发育不良患者大量的关节成形术不理想的结果,一个非常重要的因素是康复预后的构建——在考虑疾病特点和患者能力的情况下,估计达到预期康复目标或实现康复潜力的概率。目的:确定发育不良髋关节的重要参数,其改变对髋关节置换术后下肢肌力缺损的影响及康复潜力的前景。材料和方法。对23例发育不良髋关节进行x线检查。测量以下放射学参数:髋臼深度;地板厚度;髋臼深度指数;外展力臂;重力力臂;股骨头旋转中心相对于髋臼旋转中心的高度和偏侧。为了客观化单腿站立时维持骨盆平衡所需的肌肉力量平衡,作者创建了一个数学模型,该模型反映了骨盆与股骨的关系以及髋关节外展肌和内收肌两组肌肉的作用向量。结果。采用骨盆水平平衡模型,计算关节置换术前后患者的肌力缺损水平。结果发现,其中一些人仍然存在肌肉力量不足。通过线性回归模型,建立了确定肌肉力量不足的方程。经统计分析,回归方程结果与数学模型结果无差异(p >> 0.05)。回归分析表明,影响结果最显著的因素是颈轴角、地板厚度和头高。为了确定影响关节置换术结果的放射学参数的限度,根据计算肌力缺损程度将患者分为4组:ⅰ组缺损大于20%,ⅱ组缺损小于20%,ⅲ组剩余20%,ⅳ组剩余20%以上。一般情况下,患者的肌力会得到改善,但关节置换术后的初始缺陷会对结果产生很大影响。对于第一组患者,术前和术后的康复是必要的,以达到积极的结果。第二组以增强肌力为主要康复方向。对于第三组和第四组患者,可采用一般康复措施。结论。影响关节置换术后肌力的最重要参数是患者术前肌力和体重。另一个重要的指标是髋臼底的厚度。体重减轻是任何关节置换术后患者治疗成功的主要标准。
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Burns & Trauma
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