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Development of a micromodel that recapitulates multiple mechanical properties to mimic the complex mechanical microenvironment is crucial for cell‐based research. Herein, a microsystem combining structure of hydrogel matrix and acoustic streaming (AS) to mimic the cellular microenvironment is proposed, which can realize multiplex cellular mechanical cues, including matrix stiffness, fluid shear stress (FSS) generated by AS, and matrix roughness. The results demonstrate that the cell spreading area enlarges with the increase of matrix stiffness, and cell spreading is encouraged by integrin β1 cluster to polymerize actin when combines the hydrogel matrix with FSS. In addition, FSS has the influence on the roughness of the hydrogel, which further affects the cell morphology and mechanical properties, inducing mesenchymal stem cells (MSCs) differentiation into astrocytes rapidly. Meanwhile, cell migration is also enhanced by FSS stimulation, particularly, undifferentiated cells at 22 kPa hydrogel have the fastest migration speed, and change the movement model from contact inhibition to contact stimulation migration. Especially, matrix roughness and stiffness dominantly control of cell spreading and differentiation, whereas FSS affects cell migration. In conclusion, the microsystem in this work shows superior performance in regulating the spreading, differentiation, and migration of MSCs, which provides a new tool for cell‐microenvironment study. [ABSTRACT FROM AUTHOR]

Zhaoming Deng,1,2 Lerong Yu,1,2 Yishen Kuang,1,2 Ziyao Zhou,1,2 Xiangwei Li1 1Department of Stomatology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai City, 519000, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai City, 519000, People’s Republic of ChinaCorrespondence: Xiangwei Li, The Fifth Affiliated Hospital of Sun Yat-Sen University, East Meihua Road No. 52, Xiangzhou District, Zhuhai City, Guangdong Province, People’s Republic of China, Email lixiangwei@126.comBackground: Titanium (Ti) surface with nanotubes array via anodization has been used in dental implants to enhance bone regeneration but little research was carried out to evaluate whether the presence of highly ordered or disorderly distributed nanotubes array on titanium surface would have an effect on cell behaviors of gingival fibroblasts.Methods: The present study fabricated nanotubes arrays with varied topography under different constant voltage of electrochemical anodization in fluorine-containing electrolyte. Human gingival fibroblasts (HGFs) from extracted third molar were harvested and co-cultured with titanium disks with different nanotubes topography. Then cell behaviors of gingival fibroblasts including cell proliferation, adhesive morphology and cell migration were estimated to investigate the influence of titanium nanotubes on cell biology. Besides, gene and protein expression of adhesion molecule (integrin β 1/β 4/α 6, fibronectin, intracellular adhesion molecule-1 and collagen type I) were detected to evaluate the influence of different surfaces on cell adhesion.Results: Highly ordered arrays of nanotubes with pore diameter of 60 nm and 100 nm were fabricated under 30 and 40 V of anodization (TNT-30 and TNT-40) while disorderedly distributed nanotube arrays formed on the titanium surface under 50 V of anodization (TNT-50). Our results demonstrated that compared with raw titanium surface and disorderly nanotubes, surface with orderly nanotubes array increased cell area and aspect ratio, as well as cell migration ability in the early phase of cell adhesion (p< 0.05). Besides, compared with raw titanium surface, gene and protein expression of adhesion molecules were upregulated in nanotubes groups to different extents, no matter whether in an orderly or disorderly array.Conclusion: Within the limitations of our study, we conclude that compared with raw titanium surface, the presence of nanotubes array on titanium surface could enhance cells adhesion and cell migration in the early phase. And compared with disorderly distributed nanotubes, highly ordered nanotubes array might provide a much more favorable surface for gingival fibroblasts to achieve a tight adhesion on the materials. Keywords: nanotubes, gingival fibroblast, cell behaviors, cell adhesion, gingival sealing

The extracellular microenvironment is a highly dynamic network of biophysical and biochemical elements, which surrounds cells and transmits molecular signals. Extracellular microenvironment controls are of crucial importance for the ability to direct cell behavior and tissue regeneration. In this review, we focus on the different components of the extracellular microenvironment, such as extracellular matrix (ECM), extracellular vesicles (EVs) and growth factors (GFs), and introduce engineering approaches for these components, which can be used to achieve a higher degree of control over cellular activities and behaviors for tissue regeneration. Furthermore, we review the technologies established to engineer native-mimicking artificial components of the extracellular microenvironment for improved regenerative applications. This review presents a thorough analysis of the current research in extracellular microenvironment engineering and monitoring, which will facilitate the development of innovative tissue engineering strategies by utilizing different components of the extracellular microenvironment for regenerative medicine in the future.

Circular RNAs (circRNAs) can play essential roles in tumor development, including glioblastoma (GBM). The current study was performed to explore the function and mechanism of circ_0027446 in GBM progression. Circ_0027446, microRNA-346 (miR-346) and Phosphoglycerate kinase 1 (PGK1) levels were detected using reverse transcription-quantitative polymerase chain reaction assay. Cell behaviors were examined using Cell Counting Kit-8 assay, colony formation assay, EdU assay, flow cytometry, and transwell assay. Glycolytic metabolism was analyzed by commercial kits. The protein level was determined via western blot. The target interaction was analyzed by dual-luciferase reporter assay. Circ_0027446 function in vivo was explored by tumor xenograft assay. Circ_0027446 expression was significantly up-regulated in GBM samples and cells. Circ_0027446 down-regulation suppressed proliferation, invasion, glycolytic metabolism and enhanced apoptosis of GBM cells. MiR-346 was a target of circ_0027446, and circ_0027446 promoted GBM progression by sponging miR-346. PGK1 acted as a target gene of miR-346, and circ_0027446 interacted with miR-346 to regulate PGK1 expression. Overexpression of miR-346 inhibited malignant behaviors of GBM cells through down-regulating PGK1. Circ_0027446 contributed to tumor growth in vivo via miR-346/PGK1 axis. The current evidences demonstrated that circ_0027446 facilitated malignant progression of GBM through binding to miR-346 to up-regulate PGK1. [ABSTRACT FROM AUTHOR]

Using injectable hydrogels loaded with mesenchymal stem cells (MSCs) to repair chondral defects is a new trend of cartilage tissue engineering in recent years. In this study, hyaluronic acid (HA) hydrogels containing the system of sustained-release Kartogenin (KGN) and modified by RGD and HAV peptides were used to facilitate repair of cartilage defect in the knee joint of rabbits. Different groups of implants were injected into osteochondral defects, and samples were taken 4 weeks after operation. Through the qualitative and quantitative analysis of Micro-CT, it can be seen that both FH (unloaded cell group) and R + FH groups (allogeneic cell group) can repair osteochondral defects well, and the amount of bone formation is high, which is close to the intact cartilage groups. Macroscopic observation and histological staining analysis showed that except for the intact cartilage group, FH group obtained the highest score. The morphology of the cartilage tissue in the FH groups was more regular and continuous than that in R + FH and H + FH (xenogeneic cell group) groups, approaching that of native cartilage. Immunohistochemical staining of Collagen II (Col II) showed that the expression and morphology of Col II in FH groups were similar to those in intact cartilage tissue. Interestingly, through in vivo experiments, this functionalized hyaluronic acid hydrogel can effectively promote the rapid repair of rabbit knee cartilage defects within one month. Graphical Abstract [ABSTRACT FROM AUTHOR]

Aquaporins (AQPs), transmembrane water-conducting channels, have earned a great deal of scrutiny for their critical physiological roles in healthy and disease cell states, especially in the biomedical field. Numerous methods have been implemented to elucidate the involvement of AQP-mediated water transport and downstream signaling activation in eliciting whole cell, tissue, and organ functional responses. To modulate these responses, other methods have been employed to investigate AQP druggability. This review discusses standard in vitro , in vivo , and in silico methods for studying AQPs, especially for biomedical and mammalian cell biology applications. We also propose some new techniques and approaches for future AQP research to address current gaps in methodology. [ABSTRACT FROM AUTHOR]

To form fully functional four-chambered structure, mammalian heart development undergoes a transient finger-shaped trabeculae, crucial for efficient contraction and exchange for gas and nutrient. Although its developmental origin and direct relevance to congenital heart disease has been studied extensively, the time-resolved cellular mechanism underlying hypotrabeculation remains elusive. Here, we employed in toto live imaging and reconstructed the holistic cell lineages and cellular behavior landscape of control and hypotrabeculed hearts of mouse embryos from E9.5 for up to 24 h. Compared to control, hypotrabeculation in ErbB2 mutants arose mainly through dual mechanisms: both reduced proliferation of trabecular cardiomyocytes from early cell fate segregation and markedly impaired oriented cell division and migration. Further examination of mosaic mutant hearts confirmed alterations in cellular behaviors in a cell autonomous manner. Thus, our work offers a framework for continuous live imaging and digital cell lineage analysis to better understand subtle pathological alterations in congenital heart disease.

Cell microenvironments in human body are always complex, dynamic, and asymmetric. Light-controlled materials can mimic different physical and chemical environments non-invasively, in site, and dynamically, as a result, is attracting increasing attention in tissue engineering, cancer biology, and regenerating medicine. In this review, we discuss different light-controlled materials regulating cell behaviors. By controlling mechanical or cell adhesion properties, these materials synthesized by functional proteins or light-sensitive chemical groups can mimic microenvironments and regulate cell behaviors like migration and differentiation.

Pluripotent stem cells (PSCs) are important for future regenerative medicine therapies. However, in the production of PSCs and derivatives, the control of culture-induced fluctuations in the outcome of cell quality remains challenging. A detailed mechanistic understanding of how PSC behaviors are altered in response to biomechanical microenvironments within a culture is necessary for rational bioprocessing optimization. In this review, we discuss recent insights into the role of cell behavioral and mechanical homeostasis in modulating the states and functions of PSCs during culture processes. We delineate promising ways to manipulate the culture variability through regulating cell behaviors using currently developed tools. Furthermore, we anticipate their potential implementation for designing a culture strategy based on the concept of Waddington's epigenetic landscape that may provide a feasible solution for tuning the culture quality and stability in the bioprocessing space. [ABSTRACT FROM AUTHOR]

Hydrogels have been extensively used as scaffolds in tissue engineering for cell adhesion, proliferation, migration, and differentiation because of their high-water content and biocompatibility similarity to the extracellular matrix. However, submicron or nanosized pore networks within hydrogels severely limit cell survival and tissue regeneration. In recent years, the application of macroporous hydrogels in tissue engineering has received considerable attention. The macroporous structure not only facilitates nutrient transportation and metabolite discharge but also provides more space for cell behavior and tissue formation. Several strategies for creating and functionalizing macroporous hydrogels have been reported. This review began with an overview of the advantages and challenges of macroporous hydrogels in the regulation of cellular behavior. In addition, advanced methods for the preparation of macroporous hydrogels to modulate cellular behavior were discussed. Finally, future research in related fields was discussed. [ABSTRACT FROM AUTHOR]

Ovarian cancer is often not diagnosed until it is in advanced stages and its cure rate is relatively low. Thus, this investigation is concerned about the pathogenesis of this cancer. Differential expression analysis was undertaken on messenger RNA (mRNA) and microRNA (miRNA) data of ovarian cancer in Gene Expression Profiling Interactive Analysis and Gene Expression Omnibus databases. RAB11A mRNA and miR-193a-5p expression levels were tested by quantitative polymerase chain reaction. The targeting relationship between RAB11A and miR-193a-5p was verified by dual-luciferase assay. Cell behaviors of ovarian cancer were tested by Cell-Counting-Kit-8, colony formation and transwell assays. Expression of RAB11A protein and the proteins associated with Wnt/β-catenin was tested by western blot. RAB11A high expression and miR-193a-5p low expression were found in ovarian cancer cells. RAB11A was targeted by miR-193a-5p. Cellular function experiments proved that RAB11A facilitated Wnt/β-catenin signaling activation and deteriorated ovarian cancer progression. Rescue experiments exhibited two results: miR-193a-5p hindered proliferation, migration and invasion of ovarian cancer cells, and this suppression was counteracted by overexpression of RAB11A and miR-193a-5p. Furthermore, miR-193a-5p repressed RAB11A-mediated Wnt/β-catenin activation. Altogether, miR-193a-5p served as a modulator in ovarian cancer cells via targeting RAB11A. • RAB11A was found for the first time to be highly expressed in ovarian cancer and aggravated the malignant phenotypes of cells. • RAB11A was a novel direct target gene of miR-193a-5p in ovarian cancer cells. • MiR-193a-5p inhibits malignant progression of ovarian cancer by targeting RAB11A. [ABSTRACT FROM AUTHOR]

Nanofibrous biomaterials, because of their structural similarity to the extracellular matrix, can be employed as a scaffold in tissue engineering. The use of biopolymers to nanofibers fabrication attracts a great deal of attention. However, sometimes these nanofibers do not support specific cell behaviors. To address this drawback, surface modification of these structures has been actively investigated. Just a while ago, nanofibrous scaffolds have been modified employing various techniques to provide an appropriate microenvironment for protecting cell functions. Modification of bulk or surfaces of the nanofibrous scaffolds via different methods can promote cell adhesion, growth, proliferation, migration, and differentiation. In this paper, we are going to discuss the different and new approaches to surface modification of polymeric nanofibers that can influence scaffolds characteristics. Surface modification of nanofibrous scaffolds can improve physical & chemical properties especially cellular behaviors. [ABSTRACT FROM AUTHOR]

Cell adhesion is a basic requirement for anchorage-dependent cells to survive on the matrix. It is the first step in a series of cell activities, such as cell diffusion, migration, proliferation, and differentiation. In vivo, cells are surrounded by extracellular matrix (ECM), whose physical and biochemical properties and micromorphology may affect and regulate the function and behavior of cells, causing cell reactions. Cell adhesion is also the basis of communication between cells and the external environment and plays an important role in tissue development. Therefore, the significance of studying cell adhesion in vitro has become increasingly prominent. For instance, in the field of tissue engineering and regenerative medicine, researchers have used artificial surfaces of different materials to simulate the properties of natural ECM, aiming to regulate the behavior of cell adhesion. Understanding the factors that affect cell behavior and how to control cell behavior, including cell adhesion, orientation, migration, and differentiation on artificial surfaces, is essential for materials and life sciences, such as advanced biomedical engineering and tissue engineering. This article reviews various factors affecting cell adhesion as well as the methods and materials often used in investigating cell adhesion.

Abstract It is well known that microRNAs (miRNAs) are crucial regulatory factors in tumorigenesis, as tumor suppressors or cancer‐promoting factors. However, the study of endometrial carcinoma relevance in miR‐522 is rare, indicating an undefined molecular mechanism for its role. Therefore, we performed this study to examine the role of miR‐522 on the biological behaviors of endometrial carcinoma. In this work, we found that miR‐522 was highly expressed in endometrial carcinoma and negatively regulated monoamine oxidase B (MAOB) expression. They also have the opposite effect on prognosis of endometrial carcinoma patients. More importantly, miR‐522 could decreased MAOB expression by binding to MAOB with a putative site, thereby promoting cell proliferation, migration, and invasion through in vitro functional analyses, including MTT assay, wound‐healing and transwell invasion experiments. Upregulation of MAOB rescued the impacts of miR‐522 mimic on cell behaviors. In conclusion, our observations demonstrated that miR‐522 accelerated the progression of endometrial carcinoma by inhibiting MAOB, which might lead to a novel therapeutic therapy for endometrial carcinoma.

Hydrogels have been extensively used as scaffolds in tissue engineering for cell adhesion, proliferation, migration, and differentiation because of their high-water content and biocompatibility similarity to the extracellular matrix. However, submicron or nanosized pore networks within hydrogels severely limit cell survival and tissue regeneration. In recent years, the application of macroporous hydrogels in tissue engineering has received considerable attention. The macroporous structure not only facilitates nutrient transportation and metabolite discharge but also provides more space for cell behavior and tissue formation. Several strategies for creating and functionalizing macroporous hydrogels have been reported. This review began with an overview of the advantages and challenges of macroporous hydrogels in the regulation of cellular behavior. In addition, advanced methods for the preparation of macroporous hydrogels to modulate cellular behavior were discussed. Finally, future research in related fields was discussed.

Background Signaling pathway analysis methods are commonly used to explain biological behaviors of disease cells. Effector genes typically decide functional attributes (associated with biological behaviors of disease cells) by abnormal signals they received. The signals that the effector genes receive can be quite different in normal vs. disease conditions. However, most of current signaling pathway analysis methods do not take these signal variations into consideration. Methods In this study, we developed a novel signaling pathway analysis method called signaling pathway functional attributes analysis (SPFA) method. This method analyzes the signal variations that effector genes received between two conditions (normal and disease) in different signaling pathways. Results We compared the SPFA method to seven other methods across 33 Gene Expression Omnibus datasets using three measurements: the median rank of target pathways, the median p-value of target pathways, and the percentages of significant pathways. The results confirmed that SPFA was the top-ranking method in terms of median rank of target pathways and the fourth best method in terms of median p-value of target pathways. SPFA’s percentage of significant pathways was modest, indicating a good false positive rate and false negative rate. Overall, SPFA was comparable to the other methods. Our results also suggested that the signal variations calculated by SPFA could help identify abnormal functional attributes and parts of pathways. The SPFA R code and functions can be accessed at https://github.com/ZhenshenBao/SPFA.

Phosphoserine phosphatase (PSPH), a key enzyme of the l‐serine synthesis pathway, has been involved in cancer progression and survival. However, limited evidence revealed the PSPH influence on hepatocellular carcinoma (HCC). Herein, we observed that PSPH expression was upregulated in both HCC tissues and cell lines, which was determined by western blotting. TCGA database showed that the PSPH protein levels were significantly upregulated and affected patient survival rates in HCC. Then gain‐ and loss‐of‐function manipulations were performed by transfection with a pcDNA‐PSPH expression vector or a specific short interfering RNA against PSPH in Huh7 cells. Huh7 cell proliferation, stemness, invasion, and apoptosis were assessed by using CCK‐8 test, colony formation assay, Transwell assay, and Flow cytometry analysis, respectively, and levels of autophagy‐related proteins were detected by using western blotting. The results showed that PSPH could induce Huh7 cell autophagy, promote cell proliferation and invasion, and inhibit apoptosis. The knockdown of PSPH could inhibit Huh7 cell proliferation, invasion, and autophagy. Furthermore, PSPH activated Liver kinase B1 (LKB1) and TGF beta‐activated kinase 1 (TAK1), affected the adenosine 5′‐monophosphate‐activated protein kinase (AMPK)/mTOR/ULK1 signaling pathway, but could not activate calcium/calmodulin‐dependent protein kinase kinase (CaMKK) in Huh7 cells. Inhibition of either LKB1, TAK1, or AMPK could eliminate the effect of PSPH overexpression on Huh7 cell behaviors. However, inhibition of CaMKK could not influence the effect of PSPH overexpression on Huh7 cell behaviors. In conclusion, PSPH could induce autophagy, promote proliferation and invasion, and inhibit apoptosis in HCC cells via the AMPK/mTOR/ULK1 signaling pathway. [ABSTRACT FROM AUTHOR]

The objective of this study is to explore the structure–property relationships of TiO2 nanotubes (TNTs) with different crystalline phases that link to protein adsorption and cell responses. Given the formation of intact rutile nanotubular structures by furnace annealing is challenge, a combination of furnace annealing and flame annealing is employed for the preparation of rutile TNTs. TNTs with pure anatase phase and mixed anatase/rutile phases are obtained by simple furnace annealing of amorphous TNTs. Results show that BSA and FBS adsorptions are greatly enhanced on rutile TNTs, whereas no discernable difference on other crystalline phases. Rutile TNTs also present highest adsorption of fibronectin and collagen which are diminished on anatase and dual anatase–rutile phases. Interestingly, however, there is no significant difference in cell proliferation or differentiation on TNTs with different crystallites. Scrutinization of the surface properties involved in protein adsorption and cell activities, a synergistic effect of surface charge, hydroxyl groups, and roughness is found on protein adsorption which further regulates cell behaviors. Those findings provide a better understanding of the structure–property relationships of titanium-based biomaterials. [ABSTRACT FROM AUTHOR]

aim of this study was to investigate the anti-cancer effects of Xiaoai Jiedu Recipe (XJR) on HCC development and its underlying mechanisms. Methods: The expression of microRNA-29a (miR-29a) and signal transducer and activator of transcription 3 (STAT3) in HCC tissues and cells was determined by quantitative real-time polymerase chain reaction. The proliferation, migration, and invasion of HCC cells were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, wound-healing, and transwell assays, respectively. The regulatory relationship between miR-29a and STAT3 in HCC was predicted by TargetScan and analyzed by luciferase reporter and RNA pull-down assays. The protein expression of matrix metalloproteinase (MMP)-2/9 and STAT3 was detected by Western blotting. A xenograft tumor mouse model was established, and tumor weight and volume were measured. Results: The expression of miR-29a was significantly decreased in HCC tissues and cells compared with that in normal tissues and cells. The up-regulation of miR-29a was related with lymph node metastasis and tumor node metastasis stage. XJR treatment significantly increased the expression of miR-29a, decreased cell viability, migration, and invasion, and reduced the protein expression of MMP-2/9 in HCC cells in a concentration-dependent manner. The anti-tumor effect of XJR on HCC cells was reversed by treatment with miR-29a inhibitor. STAT3 was predicted as a target of miR-29a, and its expression was negatively regulated by miR-29a. Moreover, STAT3 knockdown suppressed the malignant behavior of HCC cells, and its anti-tumor function was reversed by treatment with miR-29a inhibitor. Furthermore, XJR treatment inhibited tumor growth in mice through elevating miR-29a expression and inhibiting STAT3 expression. Conclusion: XJR suppressed the development of HCC via regulating miR-29a and STAT3. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptor-like-1 (FGFRL1) is important to cell motility and links with tumorigenic potential in various types of cancers. To investigate the biological function and underlying mechanism of FGFRL1 in rectal adenocarcinoma, we conducted this study. TCGA and Oncomine databases were used to analyze FGFRL1 expression and its association with clinical characteristics or overall survival (OS) in rectal adenocarcinoma patients. siRNA strategy was implemented to knockdown FGFRL1 expression in rectal adenocarcinoma cells. CCK8, colony formation, wound healing, and transwell assays were implemented to measure cell behaviors. qRT-PCR and western blot were utilized to identify mRNA and protein expression levels. FGFRL1 was significantly increased in rectal adenocarcinoma tissue samples, either colon or rectum. High-regulation of FGFRL1 expression induced poorer outcome of rectal adenocarcinoma patients. Downregulation of FGFRL1 inhibited the proliferation, colony formation, migration, and invasion of SW837 cells. The MAPK pathway-related proteins, phosphorylation of MEK and ERK, were also decreased after si-FGFRL1 transfection. These findings demonstrated that FGFRL1, acting as a potential inducator, may promote the progression of rectal adenocarcinoma via activating the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Despite investigations into microRNA (miRNA) expression in esophageal cancer (EC) tissue, miRNAs that participate in EC pathogenesis and their subsequent mechanisms of action remain to be determined. The present study aimed to identify important miRNAs that contribute to EC development, and to assess miRNA biomarkers that could be used in EC diagnosis, prognosis and therapy. Bioinformatics analysis was performed to reanalyze EC tissue miRNA expression microarray dataset GSE113776, which was followed by in vitro verification of miRNA functions using reverse transcription-quantitative PCR, western blot analysis and a dual-luciferase reporter assay. Out of 93 miRNAs extracted, only miR-200a was significantly increased in EC tissues. Transfection of KYSE150 esophageal squamous cell carcinoma (ESCC) cells with miR-200a mimics significantly increased their proliferative, migratory and invasive ability, whereas the opposite cell behaviors were observed in ESCC cells transfected with a miR-200a inhibitor. A total of six miR-200a target genes [catenin β1 (CTNNB1), cadherin-1 (CDH1), PTEN, adenomatous polyposis coli (APC), catenin α1 (CTNNA1) and superoxide dismutase 2 (SOD2)] were selected for further analysis based on Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analysis, protein-protein interaction network map data and protein expression in esophageal tissue. These target genes were downregulated under miR-200a expression and upregulated in the presence of the miR-200a inhibitor. The association between miR-200a and the 3′-untranslated region of target genes in ESCC cells was confirmed using a dual-luciferase reporter assay. In conclusion, the present study demonstrated that miR-200a may participate in the promotion of ESCC cell proliferation, migration and invasion, and provided novel evidence for the direct interaction between miR-200a and CTNNB1, CDH1, PTEN, APC, CTNNA1 and SOD2, which may contribute to the observed altered cell behavior. [ABSTRACT FROM AUTHOR]

Background: A recent study reported a novel long non-coding RNA (lncRNA) E2F-mediated cell proliferation enhancing lncRNA (EPEL, human chromosome 4, intergenic region) plays an oncogenic role in lung cancer.Aims: We aimed to investigate the role of lncRNA EPEL in gastric cancer.Methods: Gene expression was analyzed by RT-qPCR and western blot. Survival analysis was performed by comparing survival curves. Cell proliferation, migration, and invasion were analyzed by CCK-8 and Transwell assays.Results: We found that lncRNA EPEL and Runt-related transcription factor 2 (RUNX2) were both upregulated in gastric cancer. EPEL and RUNX2 were positively correlated in tumor. Patients with high expression level of lncRNA EPEL showed poor survival. LncRNA EPEL and RUNX2 overexpression promoted, while lncRNA EPEL siRNA silencing inhibited the migration, proliferation, and invasion of gastric cancers. In addition, RUNX2 overexpression completely rescued the inhibited cancer cell migration, proliferation, and invasion caused by lncRNA EPEL siRNA silencing. Consistently, EPEL overexpression resulted in upregulated RUNX2 expression, while RUNX2 overexpression did not affect lncRNA EPEL expression.Conclusions: Therefore, lncRNA EPEL may regulate cancer cell behaviors and affect prognosis of gastric cancer by interacting with RUNX2. [ABSTRACT FROM AUTHOR]

Zhaoying Wu,1 Quan Li,2 Yongkang Pan,1 Yuan Yao,1 Songchao Tang,1 Jiacan Su,2 Jung-Woog Shin,3 Jie Wei,1 Jun Zhao4,5 1Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, 2Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Biomedical Engineering, Inje University, Gimhae, Republic of Korea; 4Department of Orthodontics, 5Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China Abstract: Bioactive composite macroporous scaffold containing nanoporosity was prepared by incorporation of nanoporous magnesium silicate (NMS) into poly(butylene succinate) (PBSu) using solvent casting–particulate leaching method. The results showed that the water absorption and in vitro degradability of NMS/PBSu composite (NMPC) scaffold significantly improved compared with magnesium silicate (MS)/PBSu composite (MPC) scaffold. In addition, the NMPC scaffold showed improved apatite mineralization ability, indicating better bioactivity, as the NMPC containing nanoporosity could induce more apatite and homogeneous apatite layer on the surfaces than MPC scaffold. The attachment and proliferation of MC3T3-E1 cells on NMPC scaffold increased significantly compared with MPC scaffold, and the alkaline phosphatase (ALP) activity of the cells on NMPC scaffold was expressed at considerably higher levels compared with MPC scaffold. Moreover, NMPC scaffold with nanoporosity not only had large drug loading (vancomycin) but also exhibited drug sustained release. The results suggested that the incorporation of NMS into PBSu could produce bioactive composite scaffold with nanoporosity, which could enhance water absorption, degradability, apatite mineralization and drug sustained release and promote cell responses. Keywords: nanocomposite, degradability, apatite mineralization, cell behaviors, drug release

Abstract Background Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancer type. This study was aimed to investigate the role of microRNA‐584‐5p (miR‐584‐5p) in regulating HCC progression. Methods The expression of miR‐584‐5p in HCC cell lines was analyzed by quantitative real‐time polymerase chain reaction. Effects of miR‐584‐5p depletion on HCC cell proliferation, migration, and invasion in vitro were analyzed by cell counting kit‐8 assay, wound‐healing assay, and transwell invasion assay. miR‐584‐5p targeting potassium voltage‐gated channel subfamily E regulatory subunit 2 (KCNE2) was identified using bioinformatics algorithm and dual‐luciferase activity reporter assay. Kaplan–Meier Plotter website was used to investigate the effect of miR‐584‐5p or KCNE2 expression on the overall survival of HCC patients. Results In vitro functional assays showed miR‐584‐5p depletion decreased HCC cell proliferation, cell migration, and cell invasion. Moreover, miR‐584‐5p functions by directly targeting KCNE2, and it in turn, mediates the effects of miR‐584‐5p on HCC cell behaviors. Conclusions These results demonstrated that miR‐584‐5p functions as an oncogenic miRNA in HCC.

Background: LINC01614 was abnormally expressed in myocardial infarction and other heart failures. We attempted to detect the effects of LINC01614 in myocardial ischemia--reperfusion (I/R) injury. Methods: H9c2 cardiomyocyte cells were treated with hypoxia/reoxygenation (H/R) to establish myocardial ischemia (MI) model. Results: Clinical data of Gene Expression Omnibus (GEO) database indicated that LINC01614 was highly regulated in first acute myocardial infarction, whereas miR-138-5p was downregulated in unstable angina pectoris. LINC01614 inhibition promoted cell proliferation and repressed the apoptotic property after H/R treatment using Cell Counting Kit-8 and flow cytometry analysis. Downregulation of LINC01614 enhanced the expression of Bcl-2 but attenuated Bax and cleaved caspase 3 expression after H/R treatment. Bioinformatics prediction and dual-luciferase reporter assay determined that LINC01614 directly targeted miR-138-5p and negatively regulated the expression of miR-138-5p. Furthermore, the overexpression of miR-138-5p significantly strengthened the function of si-LINC01614 in H/R groups. Conclusion: Our results illustrated that reduction in LINC01614 attenuated H/R treatment-induced myocardial damage via sponging miR-138-5p. [ABSTRACT FROM AUTHOR]

It is well known that microRNAs (miRNAs) are crucial regulatory factors in tumorigenesis, as tumor suppressors or cancer‐promoting factors. However, the study of endometrial carcinoma relevance in miR‐522 is rare, indicating an undefined molecular mechanism for its role. Therefore, we performed this study to examine the role of miR‐522 on the biological behaviors of endometrial carcinoma. In this work, we found that miR‐522 was highly expressed in endometrial carcinoma and negatively regulated monoamine oxidase B (MAOB) expression. They also have the opposite effect on prognosis of endometrial carcinoma patients. More importantly, miR‐522 could decreased MAOB expression by binding to MAOB with a putative site, thereby promoting cell proliferation, migration, and invasion through in vitro functional analyses, including MTT assay, wound‐healing and transwell invasion experiments. Upregulation of MAOB rescued the impacts of miR‐522 mimic on cell behaviors. In conclusion, our observations demonstrated that miR‐522 accelerated the progression of endometrial carcinoma by inhibiting MAOB, which might lead to a novel therapeutic therapy for endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Tantalum exhibits excellent biocompatibility and good chemical stability, which has been employed in dental and orthopedic applications. The local microenvironment of the surface of implants influence determines the surrounding cell responses. In this work, nano-dimpled structure on the surface of pure tantalum was fabricated by electrochemical anodization. The surface morphology of the nano-dimpled structure was observed, and the dimensions of the nano-dimpled structure were measured by scanning electron microscopy (SEM). The surface roughness of the sample with nano-dimpled structure was measured by atomic force microscopy (AFM). The results show that the diameter of nano-dimpled ranges from 40 to 180 nm, and the higher the applied voltage, the larger the diameter. Moreover, nano-dimpled structure has good hydrophilicity. In vitro results show that nano-dimpled structure can promote the adhesion and proliferation of mouse cranial anterior bone (MC-3T3-E1) cells. The filopodia of MC-3T3-E1 cells can be fully extended on this nano-dimpled structure. On the surface of the nano-dimpled structure with a dimple size of 40 nm, the cells have the longest aspect ratio. The small dimple size of the nano-dimpled structure is beneficial to cell proliferation and osteogenic differentiation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Emerging evidence has indicated that microRNAs (miRNAs) play crucial roles in regulating cancer carcinogenesis; however, its role in oral squamous cell carcinoma (OSCC) remains largely unknown. Our work was aimed to investigate the role of miR- 4513 in regulating OSCC cells behaviors. MATERIALS AND METHODS: MiR-4513 expression in OSCC cells was analyzed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation, migration, invasion, and apoptosis were analyzed by the cell counting kit-8 (CCK-8) assay, wound-healing assay, transwell invasion assay, and flow cytometry, respectively. The connections of miR-4513 and CXC ligand 17 (CXCL17) were analyzed by luciferase reporter assay and Western blot assay. RESULTS: MiR-4513 expression was found elevated in the OSCC cell lines. The downregulation of miR-4513 expression inhibits cell proliferation, migration, invasion and, at the same time, promotes apoptosis. Furthermore, we validated CXCL17 as a direct target of miR-4513. Knocking down the expression of CXCL17, inhibited the effects of miR-4513 on OSCC cell behaviors. CONCLUSIONS: Our results suggested the oncogenic role of miR-4513 in OSCC, and therefore it might be used as a target for the OSCC treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mounting evidence has suggested that microRNAs (miRNAs) play crucial roles in the progression of nasopharyngeal carcinoma (NPC). However, the molecular mechanism remains not fully understood. We aimed to examine the expression and biological function of miR-122-5p in NPC. MATERIALS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction was conducted to examine the expression of miR- 122-5p. Cell Counting Kit-8 assay, colony formation assay, wound healing assay and transwell assay were performed to measure cell proliferation, colony formation, migration and invasion. Luciferase reporter assay and Western blot assay were used to confirm the target gene of miR-122-5p. RESULTS: The results showed that miR-122- 5p was significantly downregulated in NPC cell lines. Additionally, it was demonstrated that special AT-rich sequence-binding protein 1 (SATB1) was targeted by miR-122-5p. Furthermore, our results revealed that miR-122-5p inhibits cell proliferation, colony formation, cell migration and cell invasion by targeting SATB1. CONCLUSIONS: Our data suggested that miR- 122-5p functions as a tumor suppressor and may be a therapeutic target for NPC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Representative applications of CORGs are summarized. • Advantages of DNA hydrogels for CORGs development are elaborated. • The mechanisms of EVs for OA therapy and cartilage regeneration are reviewed. • An innovative strategy of EVs-loaded DNA hydrogels for CORGs engineering is proposed. Articular cartilage lesion such as osteoarthritis (OA) is becoming a serious threat to global human health. In recent years, as a new paradigm in cartilage tissue engineering and regenerative medicine, cartilage organoids (CORGs) have shown great potential in cartilage development, pathological mechanisms research and therapeutic drugs development. Functional biomaterials, especially defined hydrogels have been employed in constructing artificial extracellular matrix by precisely regulating physicochemical properties to form 3D microenvironment conducive to cells self-organization and CORGs formation. DNA hydrogels are hydrophilic polymer network formed by cross-linked DNA chains, which have good biocompatibility, biodegradability, sequence designability and adjustable versatility. Based on these advantages, DNA hydrogels not only can accurately regulate the chemical compositions, mechanical properties, topologies and respond spatiotemporally to external signals to guide cell behaviors, but also bear excellent drugs delivery ability for tissue regeneration. As a result, we believe that DNA hydrogels have great advantages for CORGs development and further application. Extracellular vesicles (EVs) from different sources have been proved to be an advance therapy for OA and significantly promote cartilage regeneration through multiple mechanisms. Engineering strategies such as directly modifying EVs or combining biomaterials have been applied to enhance efficacy of EVs. Thus, EVs as multifunctional bioactive components may play a key role in accelerating CORGs formation. In this review, we proposed an innovative strategy: EVs-loaded DNA hydrogels as promising candidate for CORGs construction and application. It is hoped that this review can provide a new insight for researchers and clinicians engaged in CORGs related research. [ABSTRACT FROM AUTHOR]

Therapeutic benefits of small caliber artificial blood vessels to cure cardio and cerebrovascular diseases are mainly limited by their low patency during long-term transplantation. Bacterial nanocellulose (BNC), as a natural polysaccharide mainly synthesized by a bacterium Komagataeibatacter xylinus , has shown great potential in small-caliber vascular graft applications due to its shape controllability, and furthermore its physical surface structure can be adjusted with different treatments. However, influences of physical surface structure and properties of BNC conduits on behaviors of vascular cells have not been investigated. In this work, mercerized BNC conduits (MBNC) with different surface roughness and stiffness were constructed by controlled alkali (NaOH) treatment. The changes of surface structures and properties significantly affected the behaviors of vascular cells and gene expression; meanwhile, the cell seeding density also affected the cell responses. After mercerization with NaOH concentration > 10 %, it was observed that the increased stiffness of MBNC decreased several functional gene expressions of human vascular endothelial cells, and the pathological transformation of smooth muscle cells was inhibited. This study demonstrates physical surface structure of MBNC conduits will critically regulate functions and behaviors of vascular cells and it also provides important designing parameters to improve the long-term patency of BNC-based conduits. [Display omitted] [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) ranks as the fifth most common malignancy worldwide. The detailed mechanism of signal regulation for HCC progression is still not known, and the high motility of cancer cells is known as a core property for cancer progression maintenance. Annexin A2 (ANXA2), a calcium-dependent phospholipids binding protein is highly expressed in HCC. To study the roles the excessively expressed ANXA2 during the progression of HCC, we inhibited the ANXA2 expression in SMMC-7721 cells using RNAi, followed by the analysis of cell growth, apoptosis and cell motility. To explore the relationship between the cell behaviors and its structures, the microstructure changes were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. Our findings demonstrated that down-regulation of ANXA2 results in decreased the cell proliferation and motility, enhanced apoptosis, suppressed cell pseudopodia/filopodia, inhibited expression of F-actin and β-tubulin, and inhibited or depolymerized Lamin B. The cell contact inhibition was also analyzed in the paper. Take together, our results indicate that ANXA2 plays an important role to enhance the malignant behaviors of HCC cells, and the enhancement is closely based on its remodeling to cell structures. [ABSTRACT FROM AUTHOR]

Min Li,1 Ying Yang2 1Department of Oncology, Changsha Central Hospital, Changsha, People’s Republic of China; 2Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of ChinaTiO2 nanotube arrays with well-ordered nanotubular structures and controllable dimensions have emerged as a favorable substrate for advanced cell culturing with regulable cell behavior and differentiation.1,2 Unfortunately, the biological effects of nanotubes with different surface features on various cell lines are still inconsistent and inconclusive. Therefore, we read with great interest the enlightening work from Tian et al3 published in the International Journal of Nanomedicine on investigating the effects and molecular mechanisms of TiO2 nanotubes with various topographies and structures on the biological behavior of cultured cells.View the original paper by Tian and colleagues.

Biocomposite nanofiber scaffolds of polycaprolactone (PCL) with different graphene oxide (GO) concentrations were prepared using electrospinning technology. The successful incorporation of GO nanosheets into PCL polymer nanofibers improved the thermal and mechanical properties of the nanofibers because of the intrinsic properties developed due to the interactions of GO and PCL. In order to estimate the biocompatibility of PCL/GO composite scaffolds, mouse marrow mesenchymal stem cells (mMSCs) and low-differentiated rat pheochromocytoma (PC12-L) cells were cultured. Initial adhesion and spreading of the mMSCs and PC12-L cells on PCL/GO composite scaffolds with moderate addition of GO (0.3 and 0.5 wt%) were significantly superior to those on pure PCL scaffolds, and the cells exhibited typical fibroblast- and neuron-like morphologies with obvious pseudopods and mature appearance, respectively. A small amount of GO did not restrain the proliferation and viability of the mMSCs and PC12-L cells, which indicated appreciable cell affinity of GO. Moreover, the hybridization of GO nanosheets and PCL polymer dramatically enhanced the differentiation of the mMSCs and PC12-L cells into osteo- and neuro-like cells, respectively. All these results suggest that PCL/GO composite nanofibers could be a promising alternative material as biocompatible scaffolds for tissue engineering. [ABSTRACT FROM AUTHOR]

Dynamic changes of morphologies in human mesenchymal stem cells (hMSCs) were investigated on dendrimer surfaces with different capacities for fibronectin adsorption by changing the polymeric generation numbers of first (G1), third (G3), and fifth (G5) generations. The amount of adsorbed fibronectin on dendrimer surfaces increased with the generation number. Time-lapse observations revealed that cells on the G1 surface maintained their shape with formation of fibronectin fibrils in the bodies, introducing to the stabilization of focal adhesion with enriched stress fibers. Cells on the G3 surface showed partial contraction with degradation of fibril structures in the trailing edge. Cells on the G5 surface changed the shape by active extension and strong contracting without stabilization of focal adhesion through the formation of fibronectin aggregates and immature stress fibers. In addition, the paxillin which is a focal adhesion protein at lamellipodia was phosphorylated, leading to active lamellipodium protrusions. These results indicate that the amount and structure of fibronectin affects dynamic hMSC behaviors through the formation of cytoskeletons and focal adhesions. [ABSTRACT FROM AUTHOR]

The use of poly( N -isopropylacrylamide) (PNIPAM) as building blocks for engineering responsive coatings and their potential use as switchable substrates such as biosensors have attracted great attention in recent years. However, few studies have been conducted regarding the cell behaviors and the related mechanism on thermos-responsive surfaces consisting of PNIPAM microgel particles. In this work, monodisperse PNIPAM microgels were synthesized and used to prepare PINPAM microgel films. Uniform microgel surfaces can be fabricated by drop-coating with the precoating of a polyethylenimine (PEI) layer. Cell experiments indicate that unlike PNIPAM polymer brushes reported with controllable detachment ability, HepG2, which is a human liver carcinoma cell line, remains adherent on the microgel films upon cooling. Surface plasmon resonance (SPR) experiments show an irreversible adsorption of serum proteins on the microgel surface upon cooling, whose adsorption is a prerequisite of cell adhesion during cell culture. This fact may account for the irreversible adhesion of HepG2 cells. [ABSTRACT FROM AUTHOR]

In addition to the topographical features and chemical properties of substrates, the mechanical properties are known as a vital regulator of cellular processes such as adhesion, proliferation, and migration, and have received considerable attention in recent years. In this work, electrochemical redox multilayers made of ferrocene-modified poly(ethylenimine) (PEI-Fc) and deoxyribonucleic acid (DNA) with controlled stiffness were used to investigate the effects of the mechanical properties of multilayers on fibroblast cell (NIH/3T3) behaviors. Redox PEI-Fc plays an essential role in inducing swelling in multilayers under an electrochemical stimulus, resulting in distinct changes in the stiffness of the multilayers. The Young's modulus varied from 2.05 to 1.07 MPa for the (PEI-Fc/DNA) multilayers by changing the oxidation time of the electrochemical treatment. We demonstrated that the adhesion, proliferation, and migration of fibroblast cells depended on the multilayers' stiffness. These results indicate that cell behaviors can be precisely controlled by electrochemical treatment, which provides a new way to prepare thin films with tunable mechanical properties with potential biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract: To investigate different cells behaviors and genotoxicity, which were driven by specific microenvironments, three patterned surfaces (pillars, wide grooves and narrow grooves) and one smooth surface were prepared by template-based technique. Vinculin is a membrane-cytoskeletal protein in focal adhesion plaques and associates with cell–cell and cell–matrix junctions, which can promote cell adhesion and spreading. The immunofluorescence staining of vinculin revealed that the narrow grooves patterned substrate was favorable for L929 cell adhesion. For cell multiplication, the narrow grooves surface was fitted for the proliferation of L929, L02 and MSC cells, the pillars surface was only in favor of L929 cells to proliferate during 7days of cell cultivation. Cell genetic toxicity was evaluated by cellular micronuclei test (MNT). The results indicated that topological surfaces were more suitable for L929 cells to proliferate and maintain the stability of genome. On the contrary, the narrow grooves surface induced higher micronuclei ratio of L02 and MSC cells than other surfaces. With the comprehensive results of cell multiplication and MNT, it was concluded that the wide grooves surface was best fitted for L02 cells to proliferate and have less DNA damages, and the smooth surface was optimum for the research of MSC cells in vitro. [Copyright &y& Elsevier]

Abstract: The cytoskeleton, which is the major mechanical component of cells, supports the cell body and regulates the cellular motility to assist the cell in performing its biological functions. Several cytoskeletal network models have been proposed to investigate the mechanical properties of cells. This review paper summarizes these models with a focus on the prestressed cable network, the semi-flexible chain network, the open-cell foam, the tensegrity, and the granular models. The components, material parameters, types of connection joints, tension conditions, and the advantages and disadvantages of each model are evaluated from a structural and biological point of view. The underlying mechanisms that are associated with the morphological changes of spreading cells are expected to be simulated using a cytoskeletal model; however, it is still paid less attention most likely due to the lack of a suitable cytoskeletal model that can accurately model the spreading process. In this review article, the established cytoskeletal models are hoped to provide useful information for the development of future cytoskeletal models with different degrees of cell attachment for the study of the mechanical mechanisms underlying the cellular behaviors in response to external stimulations. [Copyright &y& Elsevier]