Cell Adhesion Properties Research Articles

Toughening Polyamidoamine Hydrogels through Covalent Grafting of Short Silk Fibers.

Linear amphoteric polyamidoamines (PAAs) are usually water-soluble, biodegradable and biocompatible. Crosslinked PAAs form in water hydrogels, retaining most of the favorable properties of their linear counterparts. The hydrogels prepared by the radical post-polymerization of the oligo-α,ω-bisacrylamido-terminated PAA called AGMA1, obtained by the polyaddition of 4-aminobutylguanidine (agmatine) with 2,2-bis(acrylamido)acetic acid, exhibit excellent cell-adhesion properties both in vitro and in vivo. However, due to their low mechanical strength, AGMA1 hydrogels cannot be sewn to biological tissues and need to be reinforced with fibrous materials. In this work, short silk fibers gave excellent results in this sense, proving capable of establishing covalent bonds with the PAA matrix, thanks to their lysine content, which provided amino groups capable of reacting with the terminal acrylamide groups of the AGMA1 precursor in the final crosslinking phase. Morphological analyses demonstrated that the AGMA1 matrix was intimately interconnected and adherent to the silk fibers, with neither visible holes nor empty volumes. The silk/H-AGMA1 composites were still reversibly swellable in water. In the swollen state, they could be sewn and showed no detachment between fibers and matrix and exhibited significantly improved mechanical properties compared with the plain hydrogels, particularly as regards their Young's modulus and elongation at break.

Deformable Nanovesicle-Loaded Gel for Buccal Insulin Delivery.

Deformable nanovesicles (DNVs) have been widely used in oral mucosal delivery studies of biomolecular drugs. However, their development for oral mucosal preparations has been limited by their physical and chemical instability, the need for small oral volumes, and the complexity of the oral microenvironment. This study aimed to develop a more suitable buccal delivery system for DNVs with improved storage stability. Preliminary stability studies investigated different gel types, the effects of different hydrophilic gel matrices, and matrix temperature sensitivity using DNVs loaded with insulin-phospholipid complex (IPC-DNVs). A temperature-sensitive gel encapsulating IPC-DNVs (IPC-DNV-TSG) prepared with 2% w/v gelatin was stable at 4 °C for three months and maintained an excellent hypoglycemic effect. The delivery efficiency of IPC-DNVs and IPC-DNV-TSG was compared using a TR146 cell model, revealing that cell viability remained high. Cellular uptake was slightly lower for IPC-DNV-TSG than for IPC-DNVs, but total transport did not differ significantly between the two groups, which may have been related to the viscosity of IPC-DNV-TSG and the hydrophilicity, cell adhesion properties, and biocompatibility of gelatin. Moreover, neither IPC-DNVs nor IPC-DNV-TSG induced significant mucosal irritation in rabbit tongue tissue sections. The study findings demonstrate a promising method for possible use as oral mucosal delivery of peptide drugs.

Chain-End Functionalization of Poly(ε-caprolactone) for Chemical Binding with Gelatin: Binary Electrospun Scaffolds with Improved Physico-Mechanical Characteristics and Cell Adhesive Properties.

Composite biocompatible scaffolds, obtained using the electrospinning (ES) technique, are highly promising for biomedical application thanks to their high surface area, porosity, adjustable fiber diameter, and permeability. However, the combination of synthetic biodegradable (such as poly(ε-caprolactone) PCL) and natural (such as gelatin Gt) polymers is complicated by the problem of low compatibility of the components. Previously, this problem was solved by PCL grafting and/or Gt cross-linking after ES molding. In the present study, composite fibrous scaffolds consisting of PCL and Gt were fabricated by the electrospinning (ES) method using non-functionalized PCL1 or NHS-functionalized PCL2 and hexafluoroisopropanol as a solvent. To provide covalent binding between PCL2 and Gt macromolecules, NHS-functionalized methyl glutarate was synthesized and studied in model reactions with components of spinning solution. It was found that selective formation of amide bonds, which provide complete covalent bonding of Gt in PCL/Gt composite, requires the presence of weak acid. With the use of the optimized ES method, fibrous mats with different PCL/Gt ratios were prepared. The sample morphology (SEM), hydrolytic resistance (FT-IR), cell adhesion and viability (MTT assay), cell penetration (fluorescent microscopy), and mechanical characteristics of the samples were studied. PCL2-based films with a Gt content of 20 wt% have demonstrated the best set of properties.

Effect of Amino Acid Substitution on Cell Adhesion Properties of Octa-arginine.

Octa-arginine (R8) is a cell-permeable peptide with excellent cell adhesion properties. Surface-immobilized R8 mediates cell attachment via cell surface receptors, such as heparan sulfate proteoglycans and integrin β1, and promotes cell spreading and proliferation. However, it is not clear how these properties are affected by specific peptide composition and if they could be improved. Here, we synthesized XR8 peptides, in which half of the original R8 arginine residues were replaced with another amino acid (X). We then aimed to investigate the effect of the substitution on cell adhesion and proliferation on XR8-conjugated agarose matrices. The XR8-matrix showed slightly better cell attachment when X was a hydrophobic or aromatic amino acid. However, hydrophobic XR8-matrices tended to promote cell proliferation to a less extent. Eventually, YR8-matrix most efficiently promoted cell adhesion, spreading, and proliferation among the XR8-matrices tested. Collectively, these observations indicate that the properties of residue X play a major role in the biological activity of XR8-matrices and shed light on the interaction between small peptides and the cell membrane. Further, YR8 is a promising cell-adhesive peptide for the development of cell culture substrates and biomaterials.

Live imaging of delamination in Drosophila shows epithelial cell motility and invasiveness are independently regulated

Delaminating cells undergo complex, precisely regulated changes in cell–cell adhesion, motility, polarity, invasiveness, and other cellular properties. Delamination occurs during development and in pathogenic conditions such as cancer metastasis. We analyzed the requirements for epithelial delamination in Drosophila ovary border cells, which detach from the structured epithelial layer and begin to migrate collectively. We used live imaging to examine cellular dynamics, particularly epithelial cells’ acquisition of motility and invasiveness, in delamination-defective mutants during the time period in which delamination occurs in the wild-type ovary. We found that border cells in slow border cells (slbo), a delamination-defective mutant, lacked invasive cellular protrusions but acquired basic cellular motility, while JAK/STAT-inhibited border cells lost both invasiveness and motility. Our results indicate that invasiveness and motility, which are cooperatively required for delamination, are regulated independently. Our reconstruction experiments also showed that motility is not a prerequisite for acquiring invasiveness.

Tuning the Cell-Adhesive Properties of Two-Component Hybrid Hydrogels to Modulate Cancer Cell Behavior, Metastasis, and Death Pathways.

This work presents a polysaccharide and protein-based two-component hybrid hydrogel integrating the cell-adhesive gelatin-tyramine (G-Tyr) and nonadhesive hyaluronic acid-tyramine (HA-Tyr) through enzyme-mediated oxidative coupling reaction. The resulting HA-Tyr/G-Tyr hydrogel reflects the precise chemical and mechanical features of the cancer extracellular matrix and is able to tune cancer cell adhesion upon switching the component ratio. The cells form quasi-spheroids on HA-Tyr rich hydrogels, while they tend to form an invasive monolayer culture on G-Tyr rich hydrogels. The metastatic genotype of colorectal adenocarcinoma cells (HT-29) increases on G-Tyr rich hydrogels which is driven by the material’s adhesive property, and additionally confirmed by the suppressed gene expressions of apoptosis and autophagy. On the other hand, HA-Tyr rich hydrogels lead the cells to necrotic death via oxidative stress in quasi-spheroids. This work demonstrates the ideality of HA-Tyr/G-Tyr to modulate cancer cell adhesion, which also has potential in preventing primary metastasis after onco-surgery, biomaterials-based cancer research, and drug testing.

Electrospun Nanofibers for Periodontal Treatment: A Recent Progress.

Periodontitis is a major threat to oral health, prompting scientists to continuously study new treatment techniques. The nanofibrous membrane prepared via electrospinning has a large specific surface area and high porosity. On the one hand, electrospun nanofibers can improve the absorption capacity of proteins and promote the expression of specific genes. On the other hand, they can improve cell adhesion properties and prevent fibroblasts from passing through the barrier membrane. Therefore, electrospinning has unique advantages in periodontal treatment. At present, many oral nanofibrous membranes with antibacterial, anti-inflammatory, and tissue regeneration properties have been prepared for periodontal treatment. First, this paper introduces the electrospinning process. Then, the commonly used polymers of electrospun nanofibrous membranes for treating periodontitis are summarized. Finally, different types of nanofibrous membranes prepared via electrospinning for periodontal treatment are presented, and the future evolution of electrospinning to treat periodontitis is described.

Engineering alginate hydrogel films with poly(3-hydroxybutyrate-co-3-valerate) and graphene nanoplatelets: Enhancement of antiviral activity, cell adhesion and electroactive properties

A new biodegradable semi-interpenetrated polymer network (semi-IPN) of two US Food and Drug Administration approved materials, poly(3-hydroxybutyrate-co-3-valerate) (PHBV) and calcium alginate (CA) was engineered to provide an alternative strategy to enhance the poor adhesion properties of CA. The synthesis procedure allows the additional incorporation of 10 % w/w of graphene nanoplatelets (GNPs), which have no cytotoxic effect on human keratinocytes. This quantity of multilayer graphene provides superior antiviral activity to the novel semi-IPN against a surrogate virus of SARS-CoV-2. Adding GNPs hardly affects the water absorption or electrical conductivity of the pure components of CA and PHBV. However, the semi-IPN's electrical conductivity increases dramatically after adding GNP due to molecular rearrangements of the intertwined polymer chains that continuously distribute the GNP nanosheets, This new hydrophilic composite biomaterial film shows great promise for skin biomedical applications, especially those that require antiviral and/or biodegradable electroconductive materials.

RSPO1-mutated keratinocytes from palmoplantar keratoderma display impaired differentiation, alteration of cell–cell adhesion, EMT-like phenotype and invasiveness properties: implications for squamous cell carcinoma susceptibility in patients with 46XX disorder of sexual development

BackgroundSecreted R-spondin (RSPO) proteins play a key role in reproductive organ development, epithelial stem cell renewal and cancer induction by reinforcing canonical Wnt signaling. We have previously reported that palmoplantar keratoderma (PPK), predisposition to cutaneous squamous cell carcinoma (SCC) development and sex reversal segregate as autosomal recessive trait in patients carrying RSPO1-mutations.Although our previous findings suggested that RSPO1 secreted from fibroblasts regulates keratinocyte growth or differentiation, the role of this protein in the epidermis remains largely unexplored. Our study was aimed at expanding the phenotypic, molecular and functional characterization of RSPO1-mutated skin and keratinocytes.ResultsCultured primary keratinocytes from PPK skin of a RSPO1-mutated XX-sex reversed patient displayed highly impaired differentiation and epithelial-mesenchymal transition (EMT)-like phenotype. Interestingly, RSPO1-mutated PPK skin expressed markers of increased proliferation, dedifferentiation and altered cell–cell adhesion. Furthermore, all these signs were more evident in SCC specimens of the patient. Cultured PPK patient’s keratinocytes exhibited increased expression of cell‒matrix adhesion proteins and extracellular matrix remodeling enzymes. Moreover, they showed invasiveness properties in an organotypic skin model in presence of PPK fibroblasts, which behave like cancer-associated fibroblasts. However, the co-culture with normal fibroblasts or treatment with the recombinant RSPO1 protein did not revert or reduce the EMT-like phenotype and invasion capability of PPK keratinocytes. Notably, RSPO1-mutated PPK fibroblasts induced a hyperproliferative and dedifferentiated phenotype of age-matched normal control plantar keratinocytes. Wnt signaling has a key role in both PPK promotion and SCC development. Accordingly, Wnt mediators were differentially expressed in both PPK keratinocytes and skin specimens of RSPO1-mutated patient compared to control.ConclusionsAltogether our data indicate that the absence of RSPO1 in patients with 46XX disorder of sexual development affects the skin microenvironment and epidermal integrity, thus contributing to the risk of SCC tumorigenesis in palmoplantar regions exposed to major frictional stresses.

Impact of Polypyridyl Ru Complexes on Angiogenesis-Contribution to Their Antimetastatic Activity.

The use of polypyridyl Ru complexes to inhibit metastasis is a novel approach, and recent studies have shown promising results. We have reported recently that Ru (II) complexes gathering two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and the one being 2,2′-bipyridine (bpy) or its derivative with a 4-[3-(2-nitro-1H-imidazol-1-yl)propyl (bpy-NitroIm) or 5-(4-{4′-methyl-[2,2′-bipyridine]-4-yl}but-1-yn-1-yl)pyridine-2-carbaldehyde semicarbazone (bpy-SC) moieties can alter the metastatic cascade, among others, by modulating cell adhesion properties. In this work, we show further studies of this group of complexes by evaluating their effect on HMEC-1 endothelial cells. While all the tested complexes significantly inhibited the endothelial cell migration, Ru-bpy additionally interrupted the pseudovessels formation. Functional changes in endothelial cells might arise from the impact of the studied compounds on cell elasticity and expression of proteins (vinculin and paxillin) involved in focal adhesions. Furthermore, molecular studies showed that complexes modulate the expression of cell adhesion molecules, which has been suggested to be one of the factors that mediate the activation of angiogenesis. Based on the performed studies, we can conclude that the investigated polypyridyl Ru (II) complexes can deregulate the functionality of endothelial cells which may lead to the inhibition of angiogenesis.

Simultaneous Substitution of Fe and Sr in Beta-Tricalcium Phosphate: Synthesis, Structural, Magnetic, Degradation, and Cell Adhesion Properties.

β-tricalcium phosphate is a promising bone graft substitute material with biocompatibility and high osteoinductivity. However, research on the ideal degradation and absorption for better clinical application remains a challenge. Now, we focus on modifying physicochemical properties and improving biological properties through essential ion co-substitution (Fe and Sr) in β-TCPs. Fe- and Sr-substituted and Fe/Sr co-substituted β-TCP were synthesized by aqueous co-precipitation with substitution levels ranging from 0.2 to 1.0 mol%. The β-TCP phase was detected by X-ray diffraction and Fourier transform infrared spectroscopy. Changes in Ca–O and P–O bond lengths of the co-substituted samples were observed through X-ray photoelectron spectroscopy. The results of VSM represent the M-H graph having a combination of diamagnetic and ferromagnetic properties. A TRIS–HCl solution immersion test showed that the degradation and resorption functions act synergistically on the surface of the co-substituted sample. Cell adhesion tests demonstrated that Fe enhances the initial adhesion and proliferation behavior of hDPSCs. The present work suggests that Fe and Sr co-substitution in β-TCP can be a candidate for promising bone graft materials in tissue engineering fields. In addition, the possibility of application of hyperthermia for cancer treatment can be expected.

Nanoencapsulation of Ru(p-cymene) Complex Bearing Ginger-based Natural Product into Liposomal Nanoformulation to Improve Its Cellular Uptake and Antiproliferative Activity.

The organometallic compounds are prospective candidates in the row of developing metallochemotherapeutics with the aim of overcoming the limitations of platinum drugs. In order to explore the anticancer properties of organometallic compounds with the natural medicines, two Ru(II)-p-cymene complexes containing the natural products, viz., 6-gingerol (6G) and benzylated-6-gingerdione (B-6GD) have been synthesized and characterized well. The phenolic group of the Ru(6G) complex facilitates its higher cell-free antioxidant activity than its analogue complex. Also, the same complex shows higher cytotoxicity toward A549 lung and HeLa-S3 cervical cancer cells than the Ru(B-6GD) complex but lower cytotoxicity toward A2058 metastatic melanoma cancer cells. Both complexes are shown to easily accumulate in melanoma cancer cells, and their degree of cytotoxicity in the same cells is found to be positively correlated with cell uptake. The cytotoxicity of complexes arises from their intracellular activity, mainly due to the induction of singlet oxygen production in cancer cells. The subcellular fractionation study shows that mitochondria and ER-Golgi membranes might be their predominant targets. Also, the mechanistic investigation revealed that Ru(B-6GD) induces caspase-dependent non-apoptotic cell death whereas Ru(6G) can induce caspase-independent non-apoptotic cell death. Furthermore, both complexes are found to moderately alter the adhesion properties of cancer cells, which is beneficial for antimetastatic treatment. Despite the potential pharmacological activity, Ru(6G) is encapsulated into polymer-supported liposomes to reduce its toxicity and further improve its anticancer potency. The π-conjugated yne-ene chain of polydiacetylene aids in the development of a stable nanoformulation, which achieved a slow release of the complex. Most importantly, the cancer cell uptake of the liposome-encapsulated Ru(6G) complex is 20 times enhanced and the total ROS formation in cancer cells is significantly increased compared to the non-encapsulated complex. However, the nanoformulation does not alter the antimetastatic potency of the encapsulated complex.

Formulation of Dermal Tissue Matrix Bioink by a Facile Decellularization Method and Process Optimization for 3D Bioprinting toward Translation Research.

Decellularized extracellular matrices (ECMs) are being extensively used for tissue engineering purposes and detergents are predominantly used for this. A facile detergent-free decellularization method is developed for dermal matrix and compared it with the most used detergent-based decellularization methods. An optimized, single-step, cost-effective Hypotonic/Hypertonic (H/H) Sodium Chloride (NaCl) solutions-based method is employed to decellularize goat skin that resulted in much higher yield than other methods. The ECM composition, mechanical property, and cytocompatibility are evaluated and compared with other decellularization methods. Furthermore, this H/H-treated decellularized dermal ECM (ddECM) exhibits a residual DNA content of <50ngmg-1 of dry tissue. Moreover, 85.64±3.01% of glycosaminoglycans and 65.53±2.9% collagen are retained compared to the native tissue, which is higher than the ddECMs prepared by other methods. The cellular response is superior in ddECM (H/H) than other ddECMs prepared by detergent-based methods. Additionally, a bioink is formulated with the ddECM (H/H), showing good shear thinning and shear recovery properties. Process optimization in terms of print speed, flow rate, and viscosity is done to obtain a bioprinting window for ddECM bioink. The printed constructs with optimized parameters have adequate mechanical and cell adhesive properties and excellent isotropic cellular alignment.

Photoreactive polymer and C,H-insertion reaction to tailor the properties of CHA/gelatin-based scaffold

A series of photoreactive polymers containing poly(N,N-dimethylacrylamide) and 2-hydroxy-(4-methacryloyloxybenzophenone), P(DMAA-n%MABP-OH), was explored to modify sheet-formed carbonated hydroxyapatite/gelatin (CHA/gelatin) scaffold. Under UV-light illumination, the benzophenones react with any C–H bonds in their vicinity through a C,H-insertion mechanism, enabling PDMAA-based hydrogel formation that is covalently attached to the gelatin. NMR spectroscopy confirmed the chemical structure of P(DMAA-n%MABP-OH) polymers with aimed n = 1, 5, 10, while GPC determined their molecular masses. The benzophenone reactivity under UV-light illumination for 0–240 min. was demonstrated using UV-Vis spectroscopy at 240–400 nm. After immobilization of P(DMAA-n%MABP-OH) onto the CHA/gelatin scaffold, typical FTIR vibration bands of both compounds could be detected on the spectra of the modified scaffolds. SEM images showed that the scaffold is highly porous with approximately 100 µm thickness. P(DMAA-n%MABP-OH) addition led to 2–3 times increase in thickness and 15–19% mass addition. Furthermore, it was shown that chemical (degradation and Ca2+ release profile), physical (4−7 swelling index), mechanical (0.06−0.17 MPa wet tensile strength and 0.2−0.8 MPa elastic modulus), and biological (cell adhesion) properties of the scaffold could be tailored by varying the photocrosslinker content. Cytotoxicity test showed that all studied CHA/gelatin-based scaffolds were nontoxic (>80% cell viability).

Fabrication of GO/ZnO nanocomposite incorporated patch for enhanced wound healing in streptozotocin (STZ) induced diabetic rats

Wound healing is one of the important processes in healthy individual. Wound healing involves four stages such as hemostasis, inflammation, proliferation and remodelling. Several chronic untreated wound conditions such as burn infections, diabetic etc., are a major problem in the healing process. Infections are the major concern worldwide. Nanomaterial with good antibacterial activity and less toxicity helps to fight infections. In this work, Graphene oxide and Zinc oxide (GO/ZnO) nanocomposite was synthesized using wet impregnation method. The nanocomposite was characterized using XRD, FTIR and TEM. Poly Vinyl alcohol (PVA) and Chitosan (Cs) were used to fabricate the polymeric patch by gel casting method. PVA is a biodegradable polymer. It is mechanically stable, non-toxic, hydrophilic and biocompatible. Cs is biocompatible and easily biodegradable polymer. It has antibacterial property and good cell adhesion property. The antibacterial activity of fabricated nanocomposite incorporated patch was tested against Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Staphylococcus aureus and Enterococcus faecium by well diffusion method. The swelling and degradation analysis were performed. In vitro analysis for PVA/Cs/GO/ZnO patch was carried using NIH 3T3 fibroblast cells. The hemocompatability and blood absorption property of the patch was observed. The fabricated patch was tested in diabetic induced wistar rats. The wound closure rate after the treatment of PVA/Cs/GO/ZnO patch was observed to be 86% on day 9. The histopathological studies confirmed that the patch does not show any toxic effect in organs. This patch can used to treat the diabetic wounds. The result confirms an enhanced wound closure in a shorter duration. The patch with nanocomposite alone up regulates the wound closure rate. It does not cause any toxic effect.

Nano Hydroxyapatite for Biomedical Applications Derived from Chemical and Natural Sources by Simple Precipitation Method.

In the past, bone fractures due to accidents were rectified by surgery and reconstruction of bone structure. In recent times, researchers have been made to find a solution by producing alternate biomaterials. Hydroxyapatite (HAp) is one of the most important bioactive materials used as a substitute for human hard tissue because of its composition being very similar to human bones and teeth. A study has proved that HAp has been used for bone regeneration in clinical trials in the mid-1980. HAp has been used as implant coatings and graft materials and also used as granules, cement, and pastes for bone regenerative applications. HAp coatings on bioimplants improved biocompatibility, bioactivity, and biological fixation. Moreover, some of the deposition methods can be employed to increase the cellular responses of bone regeneration such as sputtering, spraying, electrodeposition, and pulsed layer deposition. The researcher has prepared hydroxyapatite from chemical and natural sources. The surface area and intrinsic properties of the HAp play a vital role in bone-related applications. This can be achieved by synthesizing the HAp from natural sources rather than synthetic materials. The HAp obtained from the chemical source is not fulfilling the requirements of the natural bone. A variety of biowaste materials such as eggshell, crab shell, snail shell, bovine bone, fishbone, and fish scales are available in nature and can be converted to useful calcium source for HAp. The present study is to produce the HAp from biowaste materials like eggshell and chemical sources using the wet precipitation method. The synthesized HAp is coated on the Ti6Al4V alloy using the electrodeposition method, and it is immersed in SBF solution at 37°C for corrosion testing. The coated samples are investigated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), electrochemical study, field emission scanning electron icroscopy (FESEM), energy dispersive X-ray analysis (EDAX), AFM, and antibacterial activity with two different microorganisms. FTIR and XRD confirm the functional groups and crystallinity of the HAp. The good antibacterial activity of the HAp is observed against two bacterial strains. The corrosion studies reveal that the HAp derived from a natural source is eco-friendly and nontoxic and has excellent corrosion resistivity and cell adhesion properties. A strong bond is formed between the naturally derived HAp with bone tissue which is involved in the bio-resorption process and does not pose any side effect to the human body compared to synthetically derived HAp. In addition, the biowaste materials are converted to useful biomaterials and can reduce environmental pollution.

Research Status, Synthesis and Clinical Application of Recently Marketed and Clinical BCR-ABL Inhibitors.

Tyrosine kinases expressed by BCR-ABL fusion genes can cause changes in cell proliferation, adhesion, and survival properties, which are the main causes of chronic myelogenous leukemia (CML). Inhibiting the activity of BCR-ABL tyrosine kinase has become one of the effective methods for the treatment of chronic myelogenous leukemia. Initially, imatinib was the first small molecule of BCR-ABL tyrosine kinases inhibitors (TKIs) for the effective treatment of chronic myelogenous leukemia. Later, due to the emergence of various BCR-ABL mutations, especially T315I mutation, imatinib developed strong resistance. The second-generation kinase inhibitors dasatinib and nilotinib were able to overcome most of the mutation resistance but not T315I mutations. Therefore, in order to further overcome the problem of drug resistance, new types of KTIs such as flumatinib and radotinib have been developed, providing more options for clinical treatment. Some new drugs have entered clinical trials. In this review, two new BCRABL inhibitors (flumatinib and radotinib) and five new BCR-ABL inhibitors have been introduced into the clinical market in recent years. We reviewed their research status, synthesis methods, and clinical applications.

Glucocorticoids Preferentially Influence Expression of Nucleoskeletal Actin Network and Cell Adhesive Proteins in Human Trabecular Meshwork Cells.

Clinical use of glucocorticoids is associated with increased intraocular pressure (IOP), a major risk factor for glaucoma. Glucocorticoids have been reported to induce changes in actin cytoskeletal organization, cell adhesion, extracellular matrix, fibrogenic activity, and mechanical properties of trabecular meshwork (TM) tissue, which plays a crucial role in aqueous humor dynamics and IOP homeostasis. However, we have a limited understanding of the molecular underpinnings regulating these myriad processes in TM cells. To understand how proteins, including cytoskeletal and cell adhesion proteins that are recognized to shuttle between the cytosolic and nuclear regions, influence gene expression and other cellular activities, we used proteomic analysis to characterize the nuclear protein fraction of dexamethasone (Dex) treated human TM cells. Treatment of human TM cells with Dex for 1, 5, or 7 days led to consistent increases (by ≥ two-fold) in the levels of various actin cytoskeletal regulatory, cell adhesive, and vesicle trafficking proteins. Increases (≥two-fold) were also observed in levels of Wnt signaling regulator (glypican-4), actin-binding chromatin modulator (BRG1) and nuclear actin filament depolymerizing protein (MICAL2; microtubule-associated monooxygenase, calponin and LIM domain containing), together with a decrease in tissue plasminogen activator. These changes were independently further confirmed by immunoblotting analysis. Interestingly, deficiency of BRG1 expression blunted the Dex-induced increases in the levels of some of these proteins in TM cells. In summary, these findings indicate that the widely recognized changes in actin cytoskeletal and cell adhesive attributes of TM cells by glucocorticoids involve actin regulated BRG1 chromatin remodeling, nuclear MICAL2, and glypican-4 regulated Wnt signaling upstream of the serum response factor/myocardin controlled transcriptional activity.

Design and characterization of Persian gum/polyvinyl alcohol electrospun nanofibrous scaffolds for cell culture applications

Biocompatible electrospun nanofiber scaffolds were fabricated in this study using Persian gum (PG) and poly (vinyl alcohol) (PVA) to build an artificial extracellular matrix for cell growth. The preparation procedure involves mixing various ratios of PG/PVA to be electrospun and seeded with L929 fibroblasts. Upon addition of PG up to 60% to the solutions, a 30% decrease to around 240 μs·cm−1 is found in electrical conductivity which is in the range of semi-conductive polymers, whereas the surface tension is increased to around 3%. The fabricated scaffolds were characterized by morphological, chemical, thermal and structural analyses including SEM, FTIR spectroscopy, DSC, XRD, and tensile stress. The results showed that incorporation of 50% PG to the polymer solutions causes the formation of nanofibers with the least bead-shaped segments. All ratios of nanofibers containing PG showed significant biocompatibility with the cultured cells, which is presumably due to the radical scavenging feature of PG. The MTT and SEM analyses demonstrated that the scaffolds containing 50% PG possess the optimal cell compatibility, adhesion and proliferation properties. The fabricated PG/PVA cell culture scaffolds are potentially appropriate for wound dressing and cell culture applications in biomedicine.

Chemical structures and compositions of peptide copolymer films affect their functional properties for cell adhesion and cell viability

In this study we synthesized peptide copolymers containing benzyl glutamate (BG) moiety (to enhance cell viability) and lysine derivatives (to improve cell adhesion) for use in tissue engineering. We examined the effects of two lysine derivatives: Nε-t-butyloxycarbonyl lysine (BOCL) and Nε-carbobenzoxy lysine (CBZL). The cell behavior on the copolymer films was influenced by the functional characteristics of the copolymers, governed by their chemical structures and compositions. A BOC unit on the lysine side chain is bulkier than a CBZ unit, resulting in a rougher film surface displaying poorer adhesion. The film's hydrophilicity and cell adhesion properties were improved by increasing the CBZL content in the copolymers, due to the presence of the amide linkages of the CBZ units. The copolymer film prepared with an equal molar ratio of CBZL and BG exhibited the best cell performance, resulting from a balance in the copolymer's functional properties. The cell behavior on this film was further improved by partially hydrolyzing the copolymer to produce net positive charge, thereby increasing the hydrophilicity and cell recognition. These novel copolymers appear suitable for use as films for enhancing cell culturing during tissue engineering.