The effects of dynamic compressive loading on human mesenchymal stem cell osteogenesis in the stiff layer of a bilayer hydrogel

Bilayer hydrogels with a soft cartilage‐like layer and a stiff bone‐like layer embedded with human mesenchymal stem cells (hMSCs) are promising for osteochondral tissue engineering. The goals of this work were to evaluate the effects of dynamic compressive loading (2.5% applied strain, 1 Hz) on osteogenesis in the stiff layer and spatially map local mechanical responses (strain, stress, hydrostatic pressure, and fluid velocity). A bilayer hydrogel was fabricated from soft (24 kPa) and stiff (124 kPa) poly (ethylene glycol) hydrogels. With hMSCs embedded in the stiff layer, osteogenesis was delayed under loading evident by lower OSX and OPN expressions, alkaline phosphatase activity, and collagen content. At Day 28, mineral deposits were present throughout the stiff layer without loading but localized centrally and near the interface under loading. Local strains mapped by particle tracking showed substantial equivalent strain (~1.5%) transferring to the stiff layer. When hMSCs were cultured in stiff single‐layer hydrogels subjected to similar strains, mineralization was inhibited. Finite element analysis revealed that hydrostatic pressures ≥~600 Pa correlated to regions lacking mineralization in both hydrogels. Fluid velocities were low (~1–10 nm/s) in the hydrogels with no apparent correlation to mineralization. Mineralization was recovered by inhibiting ERK1/2, indicating cell‐mediated inhibition. These findings suggest that high strains (~1.5%) combined with higher hydrostatic pressures negatively impact osteogenesis, but in a manner that depends on the magnitude of each mechanical response. This work highlights the importance of local mechanical responses in mediating osteogenesis of hMSCs in bilayer hydrogels being studied for osteochondral tissue engineering.     

胸腺上皮肿瘤中程序性死亡蛋白1及其配体的临床研究进展

近年来，随着免疫治疗及肿瘤微环境概念的广泛普及，许多肿瘤靶向位点被人们关注并投以大量的实验研究。程序性死亡蛋白1及其配体（PD-1/PD-L1）作为目前最热门的一个免疫靶点通路，其抑制剂已经应用于多种恶性肿瘤的治疗当中。胸腺上皮肿瘤（TETs）是一种较为少见的肿瘤，目前已有证据表明PD-L1在TETs中存在高表达水平并且其与疾病的预后相关，因此本文针对PD-1/PD-L1在TETs中的临床研究进展作一综述。     

高迁移率族蛋白A2与肿瘤关系的研究进展

高迁移率族蛋白A2(HMGA2)是一种非组蛋白,本身不具有转录活性,但它可通过与染色质结合改变其结构,继而调节其他基因的转录,从而促进肿瘤的侵袭和转移。相关RNA基因能够调控HMGA2在肿瘤中的作用,同时肿瘤的侵袭性与上皮间质转化密切相关,可以通过靶向HMGA2基因治疗相关肿瘤。文章主要介绍HMGA2与肿瘤之间关系的研究进展。     

PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition

Protein phosphatase 4 regulatory subunit 1 (PP4R1) has been shown to play a role in the regulation of centrosome maturation, apoptosis, DNA repair, and tumor necrosis factor signaling. However, the function of PP4R1 in non-small-cell lung cancer remains unclear. In this study, we identify PP4R1 as an oncogene through Oncomine database mining and immunohistochemical staining, and we showed that PP4R1 is upregulated in lung cancer tissues as compared with that in normal lung tissues and correlated with a poor prognosis in lung cancer patients. Furthermore, in vitro study by wound-healing and Transwell assay showed that PP4R1 could promote migration and invasion of lung cancer cells. Mechanistic investigations revealed that PP4R1 could cooperate with high mobility group AT-hook 2 and thereby promotes epithelial-mesenchymal transition via MAPK/extracellular receptor kinase activation. Taken together, our study provides a rich resource for understanding PP4R1 in lung cancer and indicates that PP4R1 may serve as a potential biomarker in lung cancer therapies.     

优化全程护理在准分子激光上皮瓣下磨镶术中的应用效果

目的探讨优化全程护理在准分子激光上皮瓣下磨镶术中的应用效果。方法选取2017年7月至2019年7月本院收治的200例准分子激光上皮瓣下磨镶术患者作为研究对象,按照随机数字表法将其分为研究组与对照组,各100例。研究组实施优化全程护理,对照组实施常规护理。比较两组的护理效果。结果护理后,两组的SAS、SDS评分均低于护理前,且研究组低于对照组(P<0.05)。研究组的并发症总发生率低于对照组(P<0.05)。术后1、3个月,两组的视力水平均高于护理前,且研究组高于对照组(P<0.05)。研究组的护理满意度明显高于对照组(P<0.05)。结论优化全程护理应用于准分子激光上皮瓣下磨镶术中可调节患者心理状态,减少术后并发症的发生,促进视力恢复,提升护理满意度,值得临床推广应用。     

Melatonin-stimulated exosomes enhance the regenerative potential of chronic kidney disease-derived mesenchymal stem/stromal cells via cellular prion proteins

Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease-induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)-based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin-treated healthy MSCs (MT exosomes) and assessed the biological functions of MT exosome–treated MSCs isolated from patients with CKD (CKD-MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrP^C) in exosomes isolated from MSCs through the upregulation of miR-4516. Treatment with MT exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD-MSCs. MT exosomes significantly increased the level of angiogenesis-associated proteins in CKD-MSCs. In a murine hindlimb ischemia model with CKD, MT exosome–treated CKD-MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT exosome–treated CKD-MSCs via the miR-4516-PrP^C signaling axis. This study suggests that the treatment of CKD-MSCs with MT exosomes might be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD. Furthermore, miR-4516 and PrP^C could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.     

Preparing Adult Gerontology Acute Care Nurse Practitioner Students for Role Transition Through Hospital Immersion

The study explored adult gerontology acute care nurse practitioner (AGACNP) student’s self-perception of confidence and competence in essential domains of nurse practitioner (NP) skills. A preclinical hospital immersion experience was developed to improve transition to the ACACNP role. AGACNP students participated in once-weekly sessions for 3 consecutive weeks, with 14 students completing the experience over a 3-year period. Data showed a 28.7% improvement in student’s self-perception of confidence and competence, with statistically significant improvement in clinical decision-making skills and NP role. AGACNP students requested additional days and appreciated direct faculty feedback, while faculty efficiently supported AGACNP role transition.