Abstract:The onset of inflammatory bowel disease (IBD) involves many factors, including environmental parameters, microorganisms, and the immune system. Although research on IBD continues to expand, the specific pathogenesis mechanism is still unclear. Protein modification refers to chemical modification after protein biosynthesis, also known as post-translational modification (PTM), which causes changes in the properties and functions of proteins. Since proteins can be modified in different ways, such as acetylation, methylation, and phosphorylation, the functions of proteins in different modified states will also be different. Transitions between different states of protein or changes in modification sites can regulate protein properties and functions. Such modifications like neddylation, sumoylation, glycosylation, and acetylation can activate or inhibit various signaling pathways (e.g., nuclear factor-κB (NF-κB), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT)) by changing the intestinal flora, regulating immune cells, modulating the release of cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier. In this review, we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.
Abstract:Polyetheretherketone (PEEK) has been widely applied in orthopedics because of its excellent mechanical properties, radiolucency, and biocompatibility. However, the bioinertness and poor osteointegration of PEEK have greatly limited its further application. Growing evidence proves that physical factors of implants, including their architecture, surface morphology, stiffness, and mechanical stimulation, matter as much as the composition of their surface chemistry. This review focuses on the multiple strategies for the physical modification of PEEK implants through adjusting their architecture, surface morphology, and stiffness. Many research findings show that transforming the architecture and incorporating reinforcing fillers into PEEK can affect both its mechanical strength and cellular responses. Modified PEEK surfaces at the macro scale and micro/nano scale have positive effects on cell–substrate interactions. More investigations are necessary to reach consensus on the optimal design of PEEK implants and to explore the efficiency of various functional implant surfaces. Soft-tissue integration has been ignored, though evidence shows that physical modifications also improve the adhesion of soft tissue. In the future, ideal PEEK implants should have a desirable topological structure with better surface hydrophilicity and optimum surface chemistry.
Abstract:It has been revealed that hypoxia is dynamic in hypertrophic scars; therefore, we considered that it may have different effects on hypoxia-inducible factor-1α (HIF-1α) and p53 expression. Herein, we aimed to confirm the presence of a teeterboard-like conversion between HIF-1α and p53, which is correlated with scar formation and regression. Thus, we obtained samples of normal skin and hypertrophic scars to identify the differences in HIF-1α and autophagy using immunohistochemistry and transmission electron microscopy. In addition, we used moderate hypoxia in vitro to simulate the proliferative scar, and silenced HIF-1α or p53 gene expression or triggered overexpression to investigate the changes of HIF-1α and p53 expression, autophagy, apoptosis, and cell proliferation under this condition. HIF-1α, p53, and autophagy-related proteins were assayed using western blotting and immunofluorescence, whereas apoptosis was detected using flow cytometry analysis, and cell proliferation was detected using cell counting kit-8 (CCK-8) and 5-bromo-2'-deoxyuridine (BrdU) staining. Furthermore, immunoprecipitation was performed to verify the binding of HIF-1α and p53 to transcription cofactor p300. Our results demonstrated that, in scar tissue, HIF-1α expression increased in parallel with autophagosome formation. Under hypoxia, HIF-1α expression and autophagy were upregulated, whereas p53 expression and apoptosis were downregulated in vitro. HIF-1α knockdown downregulated autophagy, proliferation, and p300-bound HIF-1α, and upregulated p53 expression, apoptosis, and p300-bound p53. Meanwhile, p53 knockdown induced the opposite effects and enhanced HIF-1α, whereas p53 overexpression resulted in the same effects and reduced HIF-1α. Our results suggest a teeterboard-like conversion between HIF-1α and p53, which is linked with scar hyperplasia and regression.
Abstract:ObjectiveThe International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system classifies gestational trophoblastic neoplasia (GTN) patients into low- and high-risk groups, so that single- or multi-agent chemotherapy can be administered accordingly. However, a number of FIGO-defined low-risk patients still exhibit resistance to single-agent regimens, and the risk factors currently adopted in the FIGO scoring system possess inequable values for predicting single-agent chemoresistance. The purpose of this study is therefore to evaluate the efficacy of risk factors in predicting single-agent chemoresistance and explore the feasibility of simplifying the FIGO 2000 scoring system for GTN.MethodsThe clinical data of 578 GTN patients who received chemotherapy between January 2000 and December 2018 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were carried out to identify risk factors associated with single-agent chemoresistance in low-risk GTN patients. Then, simplified models were built and compared with the original FIGO 2000 scoring system.ResultsAmong the eight FIGO risk factors, the univariate and multivariate analyses identified that pretreatment serum human chorionic gonadotropin (hCG) level and interval from antecedent pregnancy were consistently independent predictors for both first-line and subsequent single-agent chemoresistance. The simplified model with two independent factors showed a better performance in predicting single-agent chemoresistance than the model with the other four non-independent factors. However, the addition of other co-factors did improve the efficiency. Overall, simplified models can achieve favorable performance, but the original FIGO 2000 prognostic system still features the highest discrimination.ConclusionsPretreatment serum hCG level and interval from antecedent pregnancy were independent predictors for both first-line and subsequent single-agent chemoresistance, and they had greater weight than other non-independent factors in predicting single-agent chemoresistance. The simplified model composed of certain selected factors is a promising alternative to the original FIGO 2000 prognostic system, and it shows comparable performance.
Abstract:目的:头颈鳞癌是常见的恶性肿瘤之一,预后较差。开发新的预后分子标志物对于改善头颈鳞癌患者的预后具有重要意义。因此,本研究通过整合公共癌症数据库中的头颈鳞癌表达谱数据及临床生存信息,开发了头颈鳞癌在线生存分析工具OShnscc(Online consensus Survival tool for Head and Neck Squamous Cell Carcinoma),用于评价基因mRNA表达量与头颈鳞癌患者生存时间的相关性。创新点:本研究开发的OShnscc是目前为止包含头颈鳞癌预后数据集最多、样本量最大的在线生存分析工具。用户不仅可以在多个独立数据集中分析和比较基因的预后价值,还可以利用多种临床因素如肿瘤TNM分期、肿瘤分级、年龄、性别等因素作为筛选条件进行亚组预后分析。方法:OShnscc的开发包括三部分:(1)以样本为人头颈鳞癌临床样本的基因芯片或二代测序数据且数据集样本数大于20个为筛选标准,从公共癌症数据库中收集和筛选有效的头颈鳞癌数据集;(2)使用SQL Server 2008对样本头颈鳞癌表达谱数据与样本生存时间进行回归分析,构建头颈鳞癌预后数据库;(3)采用Java语言开发在线分析系统,使用R语言进行生存分析,应用R sever服务进行Java语言与R语言的连接。结论:OShnscc是一个公开免费的在线生存分析工具(网址:http://bioinfo.henu.edu.cn/HNSC/HNSCList.jsp),为缺少生物信息学背景的医学及相关科研人员提供一个快速分析基因mRNA表达量与头颈鳞癌患者预后关系的平台,有助于推动头颈鳞癌的预后标志物开发。