Search

Having made use of the micropipette aspiration technique, we here investigated the viscoelastic properties of hepatocellular carcinoma (HTC) cells from the view of cell cycle. The synchronous G1 and S phase cells were achieved through thymine-2-desoryriboside and colchicine sequential blockage method and double thymine-2-desoryriboside blockage method, respectively. The synchronization results detected with flow cytometer showed that it could meet the requirements of the experiments nicely. Experimental results were analyzed with a standard linear solid viscoelastic model, in which an elastic element, K1, is in parallel with a Maxwell element composed of another elastic element, K2, in series with a viscous element, μ. The results indicated that high K1, K2 values and low μ value was the general characteristics of the cells; G1 phase cells had higher K1 values and low μ value than S phase cells, which endowed G1 phase cells with higher elasticity and faster passive deformability than S phase cells. The results maybe also reflected the difference of cytoskeleton between G1 and S phase cells, and suggested that G1 phase cells were more suitable for surviving and metastasis in blood circulation than S phase cells. [Copyright &y& Elsevier]

Background: Fatty acids synthesis and metabolism (FASM)-driven lipid mobilization is essential for energy production during nutrient shortages. However, the molecular characteristics, physiological function and clinical prognosis value of FASM-associated gene signatures in hepatocellular carcinoma (HCC) remain elusive. Methods: The Gene Expression Omnibus database (GEO), the Cancer Genome Atlas (TCGA), and International Cancer Genome Consortium (ICGC) database were utilized to acquire transcriptome data and clinical information of HCC patients. The ConsensusClusterPlus was employed for unsupervised clustering. Subsequently, immune cell infiltration, stemness index and therapeutic response among distinct clusters were decoded. The tumor immune dysfunction and exclusion (TIDE) algorithm was utilized to anticipate the response of patients towards immunotherapy, and the genomics of drug sensitivity in cancer (GDSC) tool was employed to predict their response to antineoplastic medications. Least absolute shrinkage and selection operator (LASSO) regression analysis and protein–protein interaction (PPI) network were employed to construct prognostic model and identity hub gene. Single cell RNA sequencing (scRNA-seq) and CellChat were used to analyze cellular interactions. The hub gene of FASM effect on promoting tumor progression was confirmed through a series of functional experiments. Results: Twenty-six FASM-related genes showed differential expression in HCC. Based on these FASM-related differential genes, two molecular subtypes were established, including Cluster1 and Cluster2 subtype. Compared with cluster2, Cluster1 subtype exhibited a worse prognosis, higher risk, higher immunosuppressive cells infiltrations, higher immune escape, higher cancer stemness and enhanced treatment-resistant. PPI network identified Acetyl-CoA carboxylase1 (ACACA) as central gene of FASM and predicted a poor prognosis. A strong interaction between cancer stem cells (CSCs) with high expression of ACACA and macrophages through CD74 molecule (CD74) and integrin subunit beta 1 (ITGB1) signaling was identified. Finally, increased ACACA expression was observed in HCC cells and patients, whereas depleted ACACA inhibited the stemness straits and drug resistance of HCC cells. Conclusions: This study provides a resource for understanding FASM heterogeneity in HCC. Evaluating the FASM patterns can help predict the prognosis and provide new insights into treatment response in HCC patients. [ABSTRACT FROM AUTHOR]

Over the past 2 decades, cancer stem cells (CSCs) have been identified as the root cause of cancer occurrence, progression, chemoradioresistance, recurrence, and metastasis. Targeting CSCs is a novel therapeutic strategy for cancer management and treatment. Liver cancer (LC) is a malignant disease that can endanger human health. Studies are increasingly suggesting that changes in the liver mechanical microenvironment are a primary driver triggering the occurrence and development of liver cancer. In this review, we summarize current understanding of the roles of the liver mechano-microenvironment and liver cancer stem cells (LCSCs) in liver cancer progression. We also discuss the relationship between the mechanical heterogeneity of liver cancer tissues and LCSC recruitment and metastasis. Finally, we highlight potential mechanosensitive molecules in LCSCs and mechanotherapy in liver cancer. Understanding the roles and regulatory mechanisms of the mechano-microenvironment and LCSCs may provide fundamental insights into liver cancer progression and aid in further development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Human bone marrow mesenchymal stem cells (hMSCs) are multipotent adult stem cells which are capable of diverse lineages commitment and are considered as a promising cell source for various tissue repair and regeneration. It is well known that mechanical stimuli regulate the biological functions of hMSCs. The purpose of this paper is to investigate the effect of mechanical stretch on cytoskeleton reorganization, gene and protein expressions of differentiation-related markers. Our findings showed that mechanical stretch induced f-actin reorganization, promoted the gene expressions of tendon-related markers including collagen type I (Col I), collagen type III (Col III), tenascin-C (TNC) and scleraxis (SCX), and decreased the gene expressions of collagen type II (Col II) and MSC-protein (MSC-p). Our studies also manifested that the protein expressions of Col I and TNC were increased, and the protein expression of Runx2 was inhibited by mechanical stretch. These results indicate that mechanical stretch may trigger the differentiation of hMSCs into tenocytes. This work provides novel insights into the differentiation of tenogenesis in a strain-induced environment and supports the therapeutic potential of hMSCs. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are a relatively rare subpopulation of tumor cell with self-renewal and tumorigenesis capabilities. CSCs are associated with cancer recurrence, progression, and chemoradiotherapy resistance. Establishing a reliable platform for CSC enrichment and study is a prerequisite for understanding the characteristics of CSCs and discovering CSC-related therapeutic strategies. Certain strategies for CSC enrichment have been used in laboratory, particularly fluorescence-activated cell sorting (FACS) and mammosphere culture. However, these methods fail to recapitulate the in vivo chemical and physical conditions in tumors, thus potentially decreasing the malignancy of CSCs in culture and yielding unreliable research results. Accumulating research suggests the promise of a biomaterial-based three-dimensional (3D) strategy for CSC enrichment and study. This strategy has an advantage over conventional methods in simulating the tumor microenvironment, thus providing a more effective and predictive model for CSC laboratory research. In this review, we first briefly discuss the conventional methods for CSC enrichment and study. We then summarize the latest advances and challenges in biomaterial-based 3D CSC platforms. Design strategies for materials, morphology, and chemical and physical cues are highlighted to provide direction for the future construction of platforms for CSC enrichment and study. [ABSTRACT FROM AUTHOR]

Cross-talk between tumor cells and mechanical stress in the tumor microenvironment has been shown to be involved in carcinogenesis. High mechanical stress in tumors can alter the metabolism and behaviors of cancer cells and cause cancer cells to attain cancer stem-like cell properties, thus driving tumor progression and promoting metastasis. The mechanical signal is converted into a biochemical signal that activates tumorigenic signaling pathways through mechanotransduction. Herein, we describe the physical changes occurring during reprogramming of cancer cell metabolism, which regulate cancer stem cell functions and promote tumor progression and aggression. Furthermore, we highlight emerging therapeutic strategies targeting mechanotransduction signaling pathways. [ABSTRACT FROM AUTHOR]

Stem cells are undifferentiated cells that can give rise to any types of cells in our body. Hence, they have been utilized for various applications, such as drug testing and disease modeling. However, for the successful of those applications, the survival and differentiation of stem cells into specialized lineages should be well controlled. Growth factors and chemical agents are the most common signals to promote the proliferation and differentiation of stem cells. However, those approaches holds several drawbacks such as the negative side effects, degradation or denaturation, and expensive. To address such limitations, nanomaterials have been recently used as a better approach for controlling stem cells behaviors. Graphene oxide is the derivative of graphene, the first two-dimensional (2D) materials in the world. Recently, due to its extraordinary properties and great biological effects on stem cells, many scientists around the world have utilized graphene oxide to enhance the differentiation potential of stem cells. In this mini review, we highlight the key advances about the effects of graphene oxide on controlling stem cell growth and various types of stem cell differentiation. We also discuss the possible molecular mechanisms of graphene oxide in controlling stem cell growth and differentiation. [ABSTRACT FROM AUTHOR]