Modular Microgel-Based Bioassembly Scaffold Induced Chondrogenic and Osteogenic Differentiation of BMSCs.

Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride (MA) and dopamine modified gelatin (GelMA-DA) are loaded with chondroitin sulfate (CS) (the obtained microgel named GC Ms) or bioactive glass (BG) (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms show good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promote chondrogenic differentiation of BMSCs, while GB Ms promote osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms are assembled integrally by bottom-up in situ cross-linking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which show a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments show that GC-GB/HM can simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects.

Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment.

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality. Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic, collectively known as ribosomopathy genes. Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer. Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development. The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established. This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile, to excavate the potential role of these genes, which have not or rarely been reported in cancer, in the disease development across cancers. We plan to establish a theoretical framework between the ribosomopathy gene and cancer development, to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

A Dual Functional Bioinspired Lubricant for Osteoarthritis Treatment and Potential Prevention.

Osteoarthritis (OA), primarily characterized by the deterioration of articular cartilage, is a highly prevalent joint-disabling disease. The pathological onset and progression of OA are closely related to cartilage lubrication dysfunction and synovial inflammation. Synergistic options targeted at restorative lubrication and anti-inflammation are expected to be the most attractive candidates to treat OA and perhaps help prevent it. Herein, a bioinspired lubricant (HA/PA@Lipo) was fabricated by combining anionic hyaluronan-graft-poly(2-acrylamide-2-methylpropanesulfonic acid sodium salt) (HA/PA) with cationic liposomes (Lipo) via electrostatic interaction. HA/PA@Lipo mimicked the lubrication complex located on the outer cartilage surface and was endowed cartilage with excellent cartilage-lubricating performances. After the antioxidant gallic acid (GA) was loaded for dual functionality, HA/PA@Lipo-GA was prepared with added anti-inflammatory properties. HA/PA@Lipo-GA showed favorable biocompatibility with C28/I2 cells, inhibited the production of reactive oxygen, and regulated the expression levels of anabolic genes and proteins. The therapeutic effects of HA/PA@Lipo-GA were evaluated using a sodium iodoacetate-induced OA rat model, and the preventive effects of HA/PA@Lipo-GA were estimated in vivo. The results suggested the robust potential of HA/PA@Lipo-GA with dual functions as a candidate option for OA treatment and prevention.

3D Spheroids Facilitate Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Hepatocyte-Like Cells via p300-Mediated H3K56 Acetylation.

Hepatocyte-like cells (HLCs) that are differentiated from mesenchymal stem cells (MSCs) provide a valuable resource for drug screening and cell-based regeneration therapy. Differentiating HLCs into 3D spheroids enhances their phenotypes and functions. However, the molecular mechanisms underlying MSCs hepatogenic differentiation are not fully understood. In this study, we generated HLCs from human adipose-derived mesenchymal stem cells (hADMSCs) in both 2D and 3D cultures. We performed an acetyl-proteomics assay on the HLCs derived from both 2D and 3D differentiation and identified a differential change in H3K56 acetylation between the 2 differentiated cells. Our findings revealed that 3D differentiation activated ALB gene transcription by increasing the acetylation level of H3K56, thereby enhancing the phenotypes and functions of HLCs and further promoting their maturation. Notably, inhibiting p300 reduced the acetylation level of H3K56 during hepatogenic differentiation, leading to decreased phenotypes and functions of HLCs, whereas activation of p300 promoted hepatogenic differentiation, suggesting that p300 plays a critical role in this process. In summary, our study demonstrates a potential mechanism through which 3D spheroids differentiation facilitates hADMSCs differentiation into HLCs by promoting p300-mediated H3K56 acetylation, which could have significant clinical applications in liver regeneration and disease modeling.

A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications.

The limitations of traditional two-dimensional (2D) cultures and animal testing, when it comes to precisely foreseeing the toxicity and clinical effectiveness of potential drug candidates, have resulted in a notable increase in the rate of failure during the process of drug discovery and development. Three-dimensional (3D) in-vitro models have arisen as substitute platforms with the capacity to accurately depict in-vivo conditions and increasing the predictivity of clinical effects and toxicity of drug candidates. It has been found that 3D models can accurately represent complex tissue structure of human body and can be used for a wide range of disease modeling purposes. Recently, substantial progress in biomedicine, materials and engineering have been made to fabricate various 3D in-vitro models, which have been exhibited better disease progression predictivity and drug effects than convention models, suggesting a promising direction in pharmaceutics. This comprehensive review highlights the recent developments in 3D in-vitro tissue models for preclinical applications including drug screening and disease modeling targeting multiple organs and tissues, like liver, bone, gastrointestinal tract, kidney, heart, brain, and cartilage. We discuss current strategies for fabricating 3D models for specific organs with their strengths and pitfalls. We expand future considerations for establishing a physiologically-relevant microenvironment for growing 3D models and also provide readers with a perspective on intellectual property, industry, and regulatory landscape.

Harpagide inhibits the TNF-α-induced inflammatory response in rat articular chondrocytes by the glycolytic pathways for alleviating osteoarthritis.

Osteoarthritis (OA) causes severe and functional dysfunction due to abnormal inflammation. The objective of this study was to evaluate the effect of Harpagide (HPG) on TNF-α-induced inflammation in vitro and in vivo. The effect of HPG on the proliferation of rat chondrocytes was studied. The anti-inflammatory effect of HPG and its molecular mechanisms were elucidated by qPCR, Western blotting, flow cytometry, metabolome analysis in vitro. In addition, the OA rat model was established, and the effect of HPG on OA was verified in vivo. We revealed 10 µM HPG demonstrated biocompatibility. The results demonstrated that HPG restored the upregulation of MMP-13, COX2, IL-1ß and IL-6 induced by TNF-α. Moreover, HPG reversed TNF-α induced degradation of the extracellular matrix of chondrocytes. TNF-α treatment induced down-regulation of the mRNA/protein levels of proliferative markers Bcl2, CDK1 and Cyclin D1 were also recovered. HPG can inhibit TNF-α-induced inflammatory response through glycolytic metabolic pathways. HPG can restore TNF-α-induced upregulation of GRP78/IRE1α, and downregulation of AMPK proteins. In vivo experiments demonstrated that after HPG treatment, the appearance and physiological structure of articular cartilage were more integrated with highly organized chondrocytes and rich cartilage matrix compared with OA group. Finally, the molecular docking of HPG and selected key factors in glycolysis results showed that HPG had good binding potential with PFKM, PFKP, PFKFB3, PKM, HK2, and PFKL. In conclusion, the results shown HPG protects and activates chondrocytes, inhibits TNF-α-induced inflammatory response by glycolysis pathway in rat articular chondrocytes, and plays a role in the treatment of OA.

Functional nano drug delivery system with dual lubrication and immune escape for treating osteoarthritis.

Local drug delivery via inter-articular injection offers a promising scenario to treat the most common joint disease, osteoarthritis (OA), which is closely associated with the increased friction or cartilage degeneration and the inflammatory syndrome of synovium. Therefore, it is quite necessary to improve the retention of drug delivery system within synovial joint, simultaneously restore the lubrication of degraded cartilage and meanwhile alleviate the inflammation. In this study, we propose a hydrophilic coating modified nano-liposome drug carrier (PMPC-Lipo) to achieve these functions. A modified chain transfer agent was utilized to polymerize 2-methacryloyloxyethyl phosphorylcholine (MPC), the obtained polymer, combined with lecithin and cholesterol, formed a liposome (PMPC-Lipo) where poly (MPC) acted as hydrophilic coating. PMPC-Lipo was found to restore the lubrication of mechanically damage cartilage (mimicking OA conditions) to the level like healthy cartilage due to the hydration lubrication. Additionally, due to the presence of poly (MPC), we also found PMPC-Lipo avoid the recognition of macrophage and thus escape from the phagocytosis to prolong its retention in synovial joint. Furthermore, after encapsulating gallic acid (GA) into PMPC-Lipo, the obtained GA-PMPC-Lipo can effectively scavenge reactive oxygen species and restore the imbalance of matrix secretion in inflammatory chondrocytes. Collectively, the proposed GA-PMPC-Lipo may provide a new idea for osteoarthritis treatment by providing both long-term effective drug action and excellent lubrication properties.

Biomimetic Hyaluronic Acid-Based Brush Polymers Modulate Chondrocyte Homeostasis via ROS/Ca2+/TRPV4.

Bionic mimics using natural cartilage matrix molecules can modulate the corresponding metabolic activity by improving the microenvironment of chondrocytes. A bionic brush polymer, HA/PX, has been found to reverse the loss of cartilage extracellular matrix (ECM) and has promising applications in the clinical treatment of osteoarthritis (OA). However, the unknown bioremediation mechanism of HA/PX severely hinders its clinical translation. In OA, the massive loss of the ECM may be attributed to a decrease in transient receptor potential vanilloid 4 (TRPV4) activity, which affects reactive oxygen species (ROS) clearance and [Ca2+]i signaling, initiating downstream catabolic pathways. In this study, we investigated the bioremediation mechanism of HA/PX in a model of interleukin 1ß (IL-1ß)-induced inflammation. Through TRPV4, HA/PX reduced ROS accumulation in chondrocytes and enhanced [Ca2+]i signaling, reflecting a short-term protection capacity for chondrocytes. In addition, HA/PX balanced the metabolic homeostasis of chondrocytes via TRPV4, including promoting the secretion of type II collagen (Col-II) and aggrecan, the major components of the ECM, and reducing the expression of matrix metal-degrading enzyme (MMP-13), exerting long-term protective effects on chondrocytes. Molecular dynamics (MD) simulations showed that HA/PX could act as a TRPV4 activator. Our results suggest that HA/PX can regulate chondrocyte homeostasis via ROS/Ca2+/TRPV4, thereby improving cartilage regeneration. Because the ECM is a prevalent feature of various cell types, HA/PX holds promising potential for improving regeneration and disease modification for not only cartilage-related healthcare but many other tissues and diseases.

Bioactive Phenylboronic Acid-Functionalized Hyaluronic Acid Hydrogels Induce Chondro-Aggregates and Promote Chondrocyte Phenotype.

Hydrogels are extensively investigated as biomimetic extracellular matrix (ECM) scaffolds in tissue engineering. The physiological properties of ECM affect cellular behaviors, which is an inspiration for cell-based therapies. Photocurable hyaluronic acid (HA) hydrogel (AHAMA-PBA) modified with 3-aminophenylboronic acid, sodium periodate, and methacrylic anhydride simultaneously is constructed in this study. Chondrocytes are then cultured on the surface of the hydrogels to evaluate the effect of the physicochemical properties of the hydrogels on modulating cellular behaviors. Cell viability assays demonstrate that the hydrogel is non-toxic to chondrocytes. The existence of phenylboronic acid (PBA) moieties enhances the interaction of chondrocytes and hydrogel, promoting cell adhesion and aggregation through filopodia. RT-PCR indicates that the gene expression levels of type II collagen, Aggrecan, and Sox9 are significantly up-regulated in chondrocytes cultured on hydrogels. Moreover, the mechanical properties of the hydrogels have a significant effect on the cell phenotype, with soft gels (≈2 kPa) promoting chondrocytes to exhibit a hyaline phenotype. Overall, PBA-functionalized HA hydrogel with low stiffness exhibits the best effect on promoting the chondrocyte phenotype, which is a promising biomaterial for cartilage regeneration.

Identification of hub genes and pathways in lung metastatic colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent types of malignant tumours. Metastasis is the leading cause of cancer-related mortality, with lung metastases accounting for 32.9% of all metastatic CRCs. However, since the biological mechanism of lung metastatic CRC is poorly understood, limited therapeutic targets are available. In the present study, we aimed to identify the key genes and molecular processes involved in CRC lung metastasis. METHODS: The differentially expressed genes (DEGs) between primary and lung metastatic CRC patients were obtained from the Gene Expression Omnibus (GEO) database via the GEO2R tool. The enriched biological processes and pathways modulated by the DEGs were determined with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome Gene Sets analyses. The search tool Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct a protein-protein interaction (PPI) network among DEGs. RESULTS: The DEGs were enriched in surfactant metabolism, cell-cell communication and chemokine signaling pathways. The defined hub genes were included CLU, SFTPD, CCL18, SPP1, APOE, BGN and MMP3. Among them, CLU, SFTPD and CCL18 might be associated with the specific lung tropism metastasis in CRC. In addition, the expression and prognostic values of the hub genes in CRC patients were verified in database of The Cancer Genome Atlas (TCGA) and GEO. Moreover, the protein levels of the hub genes were detected in primary and lung metastatic CRC cells, serum or tissues. Furthermore, SFTPD was confirmed to facilitate cellular proliferation and lung metastasis in CRC. CONCLUSION: This bioinformatics study may provide a better understanding of the candidate therapeutic targets and molecular mechanisms for CRC lung metastasis.

Recent Progress in Hydrogel-Based Synthetic Cartilage: Focus on Lubrication and Load-Bearing Capacities.

Articular cartilage (AC), which covers the ends of bones in joints, particularly the knee joints, provides a robust interface to maintain frictionless movement during daily life due to its remarkable lubricating and load-bearing capacities. However, osteoarthritis (OA), characterized by the progressive degradation of AC, compromises the properties of AC and thus leads to frayed and rough interfaces between the bones, which subsequently accelerates the progression of OA. Hydrogels, composed of highly hydrated and interconnected polymer chains, are potential candidates for AC replacement due to their physical and chemical properties being similar to those of AC. In this review, we summarize the recent progress of hydrogel-based synthetic cartilage, or cartilage-like hydrogels, with a particular focus on their lubrication and load-bearing properties. The different formulations, current limitations, and challenges of such hydrogels are also discussed. Moreover, we discuss the future directions of hydrogel-based synthetic cartilage to repair and even regenerate the damaged AC.

Comparative Study of Two Common In Vitro Models for the Pancreatic Islet with MIN6.

BACKGROUND: Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated ß cells or ß cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in two-dimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet ß cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. METHODS: MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. RESULTS: Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. CONCLUSION: This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.

Pancancer Analysis of the Oncogenic and Prognostic Role of NOL7: A Potential Target for Carcinogenesis and Survival.

Despite growing evidence suggesting the critical function of NOL7 in cancer initiation and development, a systematic pancancer analysis of NOL7 is lacking. Herein, we present a comprehensive study of NOL7 which aimed to explore its potential role and detailed mechanisms across 33 human tumors based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CATPAC) databases. As a result, both gene and protein levels of NOL7 were found to be increased in various tumor tissues, including breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and head and neck squamous cell carcinoma (HNSC) as compared with corresponding normal tissues. Meanwhile, dysregulated NOL7 expression was found to be closely related to pathological stage and prognosis in several cancers, including LIHC, ovarian serous cystadenocarcinoma (OV), and bladder urothelial carcinoma (BLCA). The DNA methylation level of NOL7 was found to be decreased in most cancers and to be negatively associated with NOL7 expression. Furthermore, NOL7 expression was determined to be significantly associated with levels of infiltrating cells and immune checkpoint genes, including HMGB1. Analysis of NOL7-related genes revealed that RNA metabolism pathways, including "ribosome biogenesis", "spliceosome", and "RNA transport", were mainly involved in the functional mechanism of NOL7 in human cancers. In summary, this pancancer study characterized the relationship between NOL7 expression and clinicopathologic features in multiple cancer types and further showed its potential regulatory network in human cancers. It represents a systemic analysis for further functional and therapeutic studies of NOL7 and highlights its predictive value with respect to the carcinogenesis and prognosis of various cancers, especially LIHC.

Construction and Tribological Properties of Biomimetic Cartilage-Lubricating Hydrogels.

Articular cartilage provides ultralow friction to maintain the physiological function of the knee joint, which arises from the hierarchical complex composed of hyaluronic acid, phospholipids, and lubricin, covering the cartilage surface as boundary lubrication layers. Cartilage-lubricating polymers (HA/PA and HA/PM) mimicking this complex have been demonstrated to restore the lubrication of cartilage via hydration lubrication, thus contributing to the treatment of early osteoarthritis (OA) in vivo. Here, biomimetic cartilage-lubricating hydrogels (HPX/PVA) were constructed by blending HA/PA and HA/PM (HPX) with polyvinyl alcohol (PVA) to improve the boundary lubrication and wear properties, so that the obtained hydrogels may offer a solution to the main drawbacks of PVA hydrogels used as cartilage implants. The HPX/PVA hydrogels exhibited good physicochemical and mechanical properties through hydrogen-bonding interactions, and showed lower friction and wear under the boundary lubrication and fluid film lubrication mechanisms, which remained when the hydrogels were rehydrated. Our strategy may provide new insights into exploring cartilage-inspired lubricating hydrogels.

Galactose Enhances Chondrogenic Differentiation of ATDC5 and Cartilage Matrix Formation by Chondrocytes.

Galactose, an important carbohydrate nutrient, is involved in several types of cellular metabolism, participating in physiological activities such as glycosaminoglycan (GAG) synthesis, glycosylation, and intercellular recognition. The regulatory effects of galactose on osteoarthritis have attracted increased attention. In this study, in vitro cell models of ATDC5 and chondrocytes were prepared and cultured with different concentrations of galactose to evaluate its capacity on chondrogenesis and cartilage matrix formation. The cell proliferation assay demonstrated that galactose was nontoxic to both ATDC5 cells and chondrocytes. RT-PCR and immunofluorescence staining indicated that the gene expressions of cartilage matrix type II collagen and aggrecan were significantly upregulated with increasing galactose concentration and the expression and accumulation of the extracellular matrix (ECM) protein. Overall, these results indicated that a galactose concentration below 8 mM exhibited the best effect on promoting chondrogenesis, which entitles galactose as having considerable potential for cartilage repair and regeneration.

Dual-core coaxial bioprinting of double-channel constructs with a potential for perfusion and interaction of cells.

Coaxial bioprinting of hydrogel tubes has tremendous potential in the fabrication of highly complex large-scale vascularized structures, however, constructs with bioinks of simultaneous weak printability and perfusable networks have not been reported. Here, we report a coaxial printing method in which double-channel filaments are three-dimensional (3D) extrusion-bioprinted using a customized dual-core coaxial nozzle. The filament in one channel can perform core/shell role and the other channel can play a role in perfusion. These parallel channels within filaments are separated by an interval wall of alginate, whose thickness (∼50µm) is beneficial to supplement nutrients via perfusion. Different cell-laden hydrogels of weak mechanics were used to test the adaptability and perfusability of our method, and the results showed that dynamic perfusion maintained higher viability and functions than static culture. By combining with a bioprinter, 8-layer perfusable double-channel constructs were fabricated, and the cell viabilities gradually decreased with the reduction in nutrients and oxygen in the downstream medium. Furthermore, the double-channel filaments were tested as a platform to mimic dynamic functions between cells through sequential perfusion by using Mouse insulinoma 6 (Min6) and Hepatocellular carcinoma (HepG2) as the model cells. These results demonstrated the insulin secreted by Min6 upstream simulated and increased the uptake of glucose by the downstream HepG2 cells. In conclusion, our study provided evidence for the probability of all-in-one fabrication of 3D double-channel perfusable constructs with high simplicity, expansibility, and versability. Our strategy has significant potential for building large-scale tissue constructs for applications in tissue engineering, possibly even in drug screening and regenerative medicine.

Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis.

Metastasis is the leading cause of melanoma-related mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. This study aimed to screen the core genes and molecular mechanisms related to melanoma metastasis. A gene expression profile, GSE8401, including 31 primary melanoma and 52 metastatic melanoma clinical samples, was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between melanoma metastases and primary melanoma were screened using GEO2R tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses of DEGs were performed using the Database for Annotation Visualization and Integrated Discovery (DAVID). The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape with Molecular Complex Detection (MCODE) plug-in tools were utilized to detect the protein-protein interaction (PPI) network among DEGs. The top 10 genes with the highest degrees of the PPI network were defined as hub genes. In the results, 425 DEGs, including 60 upregulated genes and 365 downregulated genes, were identified. The upregulated genes were enriched in ECM-receptor interactions and the regulation of actin cytoskeleton, while 365 downregulated genes were enriched in amoebiasis, melanogenesis, and ECM-receptor interactions. The defined hub genes included CDK1, COL17A1, EGFR, DSG1, KRT14, FLG, CDH1, DSP, IVL, and KRT5. In addition, the mRNA and protein levels of the hub genes during melanoma metastasis were verified in the TCGA database and paired post- and premetastatic melanoma cells, respectively. Finally, KRT5-specific siRNAs were utilized to reduce the KRT5 expression in melanoma A375 cells. An MTT assay and a colony formation assay showed that KRT5 knockdown significantly promoted the proliferation of A375 cells. A Transwell assay further suggested that KRT5 knockdown significantly increased the cell migration and cell invasion of A375 cells. This bioinformatics study provided a deeper understanding of the molecular mechanisms of melanoma metastasis. The in vitro experiments showed that KRT5 played the inhibitory effects on melanoma metastasis. Therefore, KRT5 may serve important roles in melanoma metastasis.

Rapid Gelling of Guar Gum Hydrogel Stabilized by Copper Hydroxide Nanoclusters for Efficient Removal of Heavy Metal and Supercapacitors.

In this paper, guar gum (GG) hydrogel has been successfully prepared by adding GG and Cu2+ mixture into an alkaline medium. The formation mechanism of the hydrogel has been investigated through various techniques. Results reveal GG facilitates the formation of ultrafine copper hydroxide clusters with a diameter of ∼3 nm. Moreover, these nanoclusters bring about a rapid gelling of GG within 10 ms. The synthesized hydrogel is applied to the adsorption of heavy metal ions from wastewater. The hydrogel shows excellent removal efficiency in removing various heavy metal ions. Besides, the hydrogel derived porous carbon exhibits high specific capacitance (281 F/g at 1 A/g) and excellent rate capacity. The high contaminant removal efficiency character and excellent electrochemical performance endow GG hydrogel with potential applications in the environmental and energy storage field.

Recent Advances in Understanding the Role of Cartilage Lubrication in Osteoarthritis.

The remarkable lubrication properties of normal articular cartilage play an essential role in daily life, providing almost frictionless movements of joints. Alterations of cartilage surface or degradation of biomacromolecules within synovial fluid increase the wear and tear of the cartilage and hence determining the onset of the most common joint disease, osteoarthritis (OA). The irreversible and progressive degradation of articular cartilage is the hallmark of OA. Considering the absence of effective options to treat OA, the mechanosensitivity of chondrocytes has captured attention. As the only embedded cells in cartilage, the metabolism of chondrocytes is essential in maintaining homeostasis of cartilage, which triggers motivations to understand what is behind the low friction of cartilage and develop biolubrication-based strategies to postpone or even possibly heal OA. This review firstly focuses on the mechanism of cartilage lubrication, particularly on boundary lubrication. Then the mechanotransduction (especially shear stress) of chondrocytes is discussed. The following summarizes the recent development of cartilage-inspired biolubricants to highlight the correlation between cartilage lubrication and OA. One might expect that the restoration of cartilage lubrication at the early stage of OA could potentially promote the regeneration of cartilage and reverse its pathology to cure OA.

Biomimetic cartilage-lubricating polymers regenerate cartilage in rats with early osteoarthritis.

The early stages of progressive degeneration of cartilage in articular joints are a hallmark of osteoarthritis. Healthy cartilage is lubricated by brush-like cartilage-binding nanofibres with a hyaluronan backbone and two key side chains (lubricin and lipid). Here, we show that hyaluronan backbones grafted with lubricin-like sulfonate-rich polymers or with lipid-like phosphocholine-rich polymers together enhance cartilage regeneration in a rat model of early osteoarthritis. These biomimetic brush-like nanofibres show a high affinity for cartilage proteins, form a lubrication layer on the cartilage surface and efficiently lubricate damaged human cartilage, lowering its friction coefficient to the low levels typical of native cartilage. Intra-articular injection of the two types of nanofibre into rats with surgically induced osteoarthritic joints led to cartilage regeneration and to the abrogation of osteoarthritis within 8 weeks. Biocompatible injectable lubricants that facilitate cartilage regeneration may offer a translational strategy for the treatment of early osteoarthritis.