A polyethylene glycol functionalized hyaluronic acid coating for cardiovascular catheter lubrication

Catheterization is a common medical operation for cardiovascular disease diagnosis and treatment, where low friction is attained through hydrophilic lubricious coatings. But these coatings can cause iatrogenic complications when particles become lose and float freely in the blood stream. Here we present an ultra-thin coating based on polyethylene glycol (PEG) functionalized hyaluronic acid (HA). The mussel-inspired biopolymer hyaluronic acid was first conjugated to dopamine (DN) to get HADN and then poly (ethylene glycol) bis (3-amino-propyl) terminated (PBA) was used to functionalize the HADN with PEG. The reciprocating sliding ball-on-flat ex vivo model based on PU ball and porcine aorta was used to evaluate the lubrication performance and the results suggest coating of HADN with best lubrication enhancement. After 40 min friction test, the surface of aorta remained intact for HADN-PBA coated PU as compared to HADN coating and positive control (sliding against bare PU). The amount of glycocalyx, number of endothelial nuclei and intima surface of aorta for coated PU were similar to negative control (without rubbing). Besides lubrication, the high biocompatibility suggests the coating of HADN-PBA is safe and lubrication benefits to the cardiovascular catheter. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

Cartilage lamina splendens inspired nanostructured coating for biomaterial lubrication

Biomaterials that are used in biological systems, such as polycarbonate urethane (PCU) knee joint implants and contact lenses, generally lack lubrication. This limits their integration with the body and impedes their function. Here, we propose a nanostructured film based on hydrophilic polysaccharide hyaluronic acid conjugated with dopamine (HADN) and zwitterionic reduced glutathione (Glu), which forms a composite coating (HADN-Glu) to enhance the lubrication between cartilage and PCU. HADN was synthesized by carbodiimide chemistry between hyaluronic acid and dopamine and deposited on PCU surface under mild oxidative conditions. Then, zwitterionic peptide-reduced glutathione was bioconjugated to HADN, forming a lubrication film. Analysis based on X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and wettability indicated that HADN and Glu had grafted successfully onto the PCU surface. Measurements of the coefficient of friction (COF), friction energy dissipation and cartilage roughness indicated that cartilage was effectively protected by the high lubrication of HADN-Glu. Both at low and high applied loads, this effect was likely due to the enhanced boundary lubrication enabled by HADN-Glu on the PCU surface. Moreover, HADN-Glu is highly biocompatible with chondrocyte cells, suggesting that this film will benefit the design of implants where lubrication is needed

A hyaluronic acid based lubricious coating for cardiovascular catheters

Hydrophilic lubricious coatings on the catheter surface reduce friction against the blood vessel wall but give rise to iatrogenic complication of particle release, embolization and thin blood vessel blockage leading to pulmonary infarction and stroke. Layer by layer deposited PLL (poly-L-lysine) and HA (hyalumnan) coating fills the urgent need of thinner lubricious coating which does not lead to release of large particles. The 8 layered PLL-HA coating was able to maintain low friction and prevent wear of endothelial glycocalyx layer (EGL). Wear and loss of EGL is a gradual process and occurred while sliding the blood vessel against bare catheter surface or 4 layered coating accompanied by epithelial cells damage and decrease in the number of nucleuses

A bioinspired mucoadhesive restores lubrication of degraded cartilage through reestablishment of lamina splendens

Adsorbed lubricious films composed of biomacromolecules are natively present at all articulating interfaces in the human body where they provide ultralow friction and maintain normal physiological function. Biolubrication gets impaired due to diseases such as osteoarthritis, in which cartilage damage results from alterations in synovial fluid and lamina splendens composition. Osteoarthritis is treated with hyaluronic acid (HA) orally or via intra-articular injection, but due to the poor adsorption of HA on the cartilage surface in the absence of adhesive molecules, pain relief is temporary. Here, we describe how natural lubrication on degraded cartilage surface can be restored with the help of a bioinspired mucoadhesive biopolymer chitosan catechol (Chi-C). Quartz crystal microbalance was used to mimic the formation of lamina splendens in vitro, known as synovial fluid conditioning films (SyCF), and colloidal probe atomic force microscopy was used to measure their nanoscale frictional properties. Clear evidence of glycoprotein (PRG4) recruitment by Chi-C increased the softness of SyCF, which also improved nanoscale lubrication in vitro, decreasing the friction coefficient from 0.06 to 0.03. At the macroscale, cartilage damage induced by Chondroitinase ABC increased the coefficient of friction (COF) from 0.07 +/- 0.04 (healthy tissue) to 0.15 +/- 0.03 (after tissue damage) in the presence of synovial fluid after sliding for 50 min. After Chi-C treatment of damaged cartilage, the COF fell to 0.06 +/- 0.03, which is comparable to healthy cartilage. Chi-C did not adversely affect the metabolic activity of human chondrocytes. This study provides new key insight into the potential for restoring biolubrication through the use of muco-adhesive molecules

Dopamine-conjugated hyaluronic acid delivered via intra-articular injection provides articular cartilage lubrication and protection

Due to its high molecular weight and viscosity, hyaluronic acid (HA) is widely used for viscosupplemen-tation to provide joint pain relief in osteoarthritis. However, this benefit is temporary due to poor adhe-sion of HA on articular surfaces. In this study, we therefore conjugated HA with dopamine to form HADN, which made the HA adhesive while retaining its viscosity enhancement capacity. We hypothesized that HADN could enhance cartilage lubrication through adsorption onto the exposed collagen type II network and repair the lamina splendens. HADN was synthesized by carbodiimide chemistry between hyaluronic acid and dopamine. Analysis of Magnetic Resonance (NMR) and Ultraviolet spectrophotometry (Uv-vis) showed that HADN was successfully synthesized. Adsorption of HADN on collagen was demonstrated using Quartz crystal microbalance with dissipation (QCM-D). Ex vivo tribological tests including measure-ment of coefficient of friction (COF), dynamic creep, in stance (40 N) and swing (4 N) phases of gait cycle indicated adequate protection of cartilage by HADN with higher lubrication compared to HA alone. HADN solution at the cartilage-glass sliding interface not only retains the same viscosity as HA and provides fluid film lubrication, but also ensures better boundary lubrication through adsorption. To confirm the cartilage surface protection of HADN, we visualized cartilage wear using optical coherence tomography (OCT) and atomic force microscopy (AFM).(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

Clinicopathological Analysis of 11 Cases of SMARCA4 (BRG1)-deficient Carcinoma

ObjectiveTo investigate the clinicopathological features, immunophenotype, diagnosis and treatment of SMARCA4 (BRG1)-deficient carcinoma. MethodsClinical data of 11 patients with SMARCA4 (BRG1)-deficient cancer were collected. The morphologic and immunohistochemical features of this tumour were summarized, and the relevant literature was reviewed. ResultsAmong the 11 cases of SMARCA4 (BRG1)-deficient carcinoma, eight were male and three were female, with median age of 60. Seven patients underwent radical resection, and four underwent traditional joint targeted chemotherapy and immunotherapy. Microscopically, the tumor cells were epithelioid, rhabdoid or spindle-shaped, with prominent eosinophilic nucleoli and frequent mitoses (>5/10 HPF). Multiple foci of necrosis were found in the tumor tissue, a large number of tumor emboli in the blood vessels and myxoid stromal degeneration. Among these cases, 11 cases showed loss of SMARCA4 (BRG1) expression, whereas the CK and Vim markers were expressed, SMARCB1 (INI1) expression was retained, and p53 mutation was detected. The tumor cells showed high proliferation activity (Ki-67>60%), and synaptophsin was moderately positive. Three cases were mismatch repair deficient and respectively showed the loss of MLH1/PMS2, PMS2 and MSH6 expression. ConclusionThe incidence of SMARCA4 (BRG1) -dificient carcinoma is low. It can be easily confused with other tumors and is difficult to be diagnosed before operation, which requires confirmation by immunohistochemistry

Construction of a prognostic assessment model for colon cancer patients based on immune-related genes and exploration of related immune characteristics

Objectives: To establish a novel risk score model that could predict the survival and immune response of patients with colon cancer.Methods: We used The Cancer Genome Atlas (TCGA) database to get mRNA expression profile data, corresponding clinical information and somatic mutation data of patients with colon cancer. Limma R software package and univariate Cox regression were performed to screen out immune-related prognostic genes. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used for gene function enrichment analysis. The risk scoring model was established by Lasso regression and multivariate Cox regression. CIBERSORT was conducted to estimate 22 types of tumor-infiltrating immune cells and immune cell functions in tumors. Correlation analysis was used to demonstrate the relationship between the risk score and immune escape potential.Results: 679 immune-related genes were selected from 7846 differentially expressed genes (DEGs). GO and KEGG analysis found that immune-related DEGs were mainly enriched in immune response, complement activation, cytokine-cytokine receptor interaction and so on. Finally, we established a 3 immune-related genes risk scoring model, which was the accurate independent predictor of overall survival (OS) in colon cancer. Correlation analysis indicated that there were significant differences in T cell exclusion potential in low-risk and high-risk groups.Conclusion: The immune-related gene risk scoring model could contribute to predicting the clinical outcome of patients with colon cancer

Zinc deficiency activates S100A8 inflammation in the absence of COX-2 and promotes murine oral-esophageal tumor progression

Zinc (Zn)-deficiency (ZD) is implicated in the pathogenesis of human oral-esophageal cancers. Previously, we showed that in ZD mice genetic deletion of cyclooxygenase-2 (Cox-2) enhances N-nitrosomethylbenzylamine-induced forestomach carcinogenesis. By contrast, Cox-2 deletion offers protection in Zn-sufficient (ZS) mice. We hypothesize that ZD activates pathways insensitive to COX-2 inhibition, thereby promoting carcinogenesis. This hypothesis is tested in a Cox-2−/− mouse tongue cancer model that mimics pharmacologic blockade of COX-2 by firstly examining transcriptome profiles of forestomach mucosa from Cox-2−/− and wild-type mice on a ZD vs. ZS diet, and secondly investigating the roles of identified markers in mouse forestomach/tongue preneoplasia and carcinomas. In Cox-2−/− mice exposed to the tongue carcinogen 4-nitroquinoline 1-oxide, dietary ZD elicited tongue/esophagus/forestomach carcinomas that were prevented by ZS. The precancerous ZD:Cox-2−/−vs. ZS:Cox-2−/− forestomach had an inflammatory signature with upregulation of the proinflammation genes S100a8 and S100a9. Bioinformatics analysis revealed overrepresentation of inflammation processes comprising S100a8/a9 and an nuclear factor (NF)-κB network with connectivity to S100A8. Immunohistochemistry revealed co-overexpression of S100A8, its heterodimeric partner S100A9, the receptor for advanced glycation end-products (RAGE), NF-κB p65, and cyclin D1, in ZD:Cox-2−/− forestomach/tongue preneoplasia and carcinomas, evidence for the activation of a RAGE-S100A8/A9 inflammatory pathway. Accumulation of p53 in these carcinomas indicated activation of additional inflammatory pathways. Zn-replenishment in ZD:Cox-2−/−mice reversed the inflammation and inhibited carcinogenesis. Thus, ZD activates alternative inflammation-associated cancer pathways that fuel tumor progression and bypass the antitumor effect of Cox-2 ablation. These findings have important clinical implications, as combination cancer therapy that includes Zn may improve efficacy