Protective and curative effects of unconjugated bilirubin on gene expression of LOX-1 and iNOS in the heart of rats receiving high-fat diet and low dose streptozotocin: a histomorphometric approach.

BACKGROUND: Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve as prognostic markers for coronary artery occlusion risk. Given the antioxidant properties of bilirubin and its inverse correlation with atherosclerosis, this study aimed to assess the beneficial effects of bilirubin on atherosclerotic indices and heart structure in high-fat diet-fed diabetic rats with atherosclerosis. METHODS: Atherosclerosis was induced in three out of five groups of adult male Sprague Dawley rats through a 14-week period of high-fat diet (HFD) consumption and a single low dose of streptozotocin (STZ) (35 mg/kg). The atherosclerotic rats were then treated with intraperitoneal administration of 10 mg/kg/day bilirubin for either 6 or 14 weeks (treated and protected groups, respectively), or the vehicle. Two additional groups served as the control and bilirubin-treated rats. Subsequently, the mRNA expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), lectin-like LDL receptor 1 (LOX-1), and the inducible nitric oxide synthase (iNOS) were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Histopathological and stereological analyses were performed to assess changes in the heart structure. RESULTS: Bilirubin significantly decreased the expression of VCAM-1, ICAM-1, LOX-1, and iNOS genes in the treated group. Moreover, bilirubin mitigated pathological damage in the left ventricle of the heart. Stereological analysis revealed a decrease in the left ventricle and myocardium volume, accompanied by an increase in vessel volume in rats treated with bilirubin. CONCLUSION: These findings demonstrate that mild hyperbilirubinemia can protect against the progression of atherosclerosis and heart failure by improving lipid profile, modulating adhesion molecules, LOX-1, and iNOS gene expression levels.

Dynamic regulation of stem cell adhesion and differentiation on degradable piezoelectric poly (L-lactic acid) (PLLA) nanofibers.

Degradable piezoelectric materials possess significant potential for application in the realm of bone tissue regeneration. However, the correlation between cell regulation mechanisms and the dynamic variation caused by material degradation has not been explained, hindering the optimization of material design and its in vivo application. Herein, piezoelectric poly (L-lactic acid) (PLLA) nanofibers with different molecular weights (MW) were fabricated, and the effects of their piezoelectric properties, structural morphology, and material products during degradation on the adhesion and osteogenic differentiation of mesenchymal stem cells (MSCs) were investigated. Our results demonstrated that cell adhesion-mediated piezoelectric stimulation could significantly enhance cell spreading, cell orientation, and upregulate the expression of calmodulin, which further triggers downstream signaling cascade to regulate osteogenic differentiation markers of type I collagen and runt-related transcription factor 2. Additionally, during the degradation of the nanofibers, the piezoelectric properties of PLLA weakened, the fibrous structure gradually diminished, and pH levels in the vicinity decreased, which resulting in reduced osteogenic differentiation capability of MSCs. However, nanofibers with higher MW (280 kDa) have the ability to maintain the fibrous morphology and piezoelectricity for a longer time, which can regulate the osteogenic differentiation of stem cells for more than 4 weeks. These findings have provide a new insight to correlate cell behavior with MW and the biodegradability of piezopolymers, which revealed an active method for cell regulation through material optimization for bone tissue engineering in near future.

Unexpected regulatory functions of cyprinid Viperin on inflammation and metabolism.

BACKGROUND: Viperin, also known as radical S-adenosyl-methionine domain containing protein 2 (RSAD2), is an interferon-inducible protein that is involved in the innate immune response against a wide array of viruses. In mammals, Viperin exerts its antiviral function through enzymatic conversion of cytidine triphosphate (CTP) into its antiviral analog ddhCTP as well as through interactions with host proteins involved in innate immune signaling and in metabolic pathways exploited by viruses during their life cycle. However, how Viperin modulates the antiviral response in fish remains largely unknown. RESULTS: For this purpose, we developed a fathead minnow (Pimephales promelas) clonal cell line in which the unique viperin gene has been knocked out by CRISPR/Cas9 genome-editing. In order to decipher the contribution of fish Viperin to the antiviral response and its regulatory role beyond the scope of the innate immune response, we performed a comparative RNA-seq analysis of viperin-/- and wildtype cell lines upon stimulation with recombinant fathead minnow type I interferon. CONCLUSIONS: Our results revealed that Viperin does not exert positive feedback on the canonical type I IFN but acts as a negative regulator of the inflammatory response by downregulating specific pro-inflammatory genes and upregulating repressors of the NF-κB pathway. It also appeared to play a role in regulating metabolic processes, including one carbon metabolism, bone formation, extracellular matrix organization and cell adhesion.

An evaluation of inflammatory and endothelial dysfunction markers as determinants of peripheral arterial disease in those with diabetes mellitus.

The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P < 0.05) different from each other. Therefore, it was concluded that the change in IL-6, IL-8, ICAM and VCAM can serve as an accurate diagnostic indicator and successful treatment.

Unveiling the synergy: Biocompatible alginate-cellulose hydrogel loaded with silk fibroin and zinc ferrite nanoparticles for enhanced cell adhesion, and anti-biofilm activity.

Combining a biocompatible hydrogel scaffold with the cell-supportive properties of silk fibroin (SF) and the unique functionalities of ZnFe2O4 nanoparticles creates a promising platform for advanced nanobiomaterials. The research is centered on synthesizing a natural hydrogel using cellulose (Cellul) and sodium alginate (SA) combined with SF and zinc ferrite nanoparticles. A range of analytical and biological assays were conducted to determine the biological and physicochemical properties of the nanobiocomposite. The hemolysis and 2,5-diphenyl-2H-tetrazolium bromide (MTT) assays indicated that the SA-Cellul hydrogel/SF/ZnFe2O4 nanobiocomposite was a biocompatible against human dermal fibroblasts (Hu02) and red blood cells (RBC). In addition, aside from demonstrating outstanding anti-biofilm activity, the nanobiocomposite also promotes the Hu02 cells adhesion, showcasing the synergistic effect of incorporating SF and ZnFe2O4 nanoparticle. These promising results show that this nanobiocomposite has potential applications in various biomedical fields.

Surface topography modulates initial platelet adhesion to titanium substrata.

The clinical success of implanted biomaterials such as dental implants is largely determined by the molecular signaling that occurs at the tissue-implant interface. The modification of surface topography is a widely-employed strategy for optimizing tissue integration with dental implants. However, little is known regarding the direct, cellular-level effects of substratum topography on platelet signaling and adhesion, despite these cells being the first to encounter the implant surface during surgical placement. Here we compared platelet adhesion and secretion on four (4) different titanium surfaces, notably, the modifications applied to commercially available dental implants: smooth (S) titanium; acid-etched (AE), sandblasted (SB) and a combined acid-etching/sandblasting procedure (SLA). Platelets were isolated from human blood, washed, and seeded on to the 4 test surfaces; platelet adhesion was quantified by microscopy. In addition, the secretion of critical molecules stored in platelet granules (platelet factor 4, PF4; soluble P-selectin, sCD62P; transforming growth factor-beta1, TGF-ß1; platelet-derived growth factor-AB, PDGF-AB) was measured by enzyme-linked immunosorbent assay (ELISA) analysis of the supernatants. There was greater platelet adhesion to the rougher AE and SB surfaces, however, the concentration of the secreted growth factors was comparable on all surfaces. We conclude that while surface topography can be engineered to modulate initial platelet adhesion, granule secretion is likely regulated as a separate and independent process.

Mechanisms of microbial co-aggregation in mixed anaerobic cultures.

Co-aggregation of anaerobic microorganisms into suspended microbial biofilms (aggregates) serves ecological and biotechnological functions. Tightly packed aggregates of metabolically interdependent bacteria and archaea play key roles in cycling of carbon and nitrogen. Additionally, in biotechnological applications, such as wastewater treatment, microbial aggregates provide a complete metabolic network to convert complex organic material. Currently, experimental data explaining the mechanisms behind microbial co-aggregation in anoxic environments is scarce and scattered across the literature. To what extent does this process resemble co-aggregation in aerobic environments? Does the limited availability of terminal electron acceptors drive mutualistic microbial relationships, contrary to the commensal relationships observed in oxygen-rich environments? And do co-aggregating bacteria and archaea, which depend on each other to harvest the bare minimum Gibbs energy from energy-poor substrates, use similar cellular mechanisms as those used by pathogenic bacteria that form biofilms? Here, we provide an overview of the current understanding of why and how mixed anaerobic microbial communities co-aggregate and discuss potential future scientific advancements that could improve the study of anaerobic suspended aggregates. KEY POINTS: • Metabolic dependency promotes aggregation of anaerobic bacteria and archaea • Flagella, pili, and adhesins play a role in the formation of anaerobic aggregates • Cyclic di-GMP/AMP signaling may trigger the polysaccharides production in anaerobes.

(Homo-)harringtonine prevents endothelial inflammation through IRF-1 dependent downregulation of VCAM1 mRNA expression and inhibition of cell adhesion molecule protein biosynthesis.

The plant alkaloid homoharringtonine (HHT) is a Food and Drug Administration (FDA)-approved drug for the treatment of hematologic malignancies. In addition to its well-established antitumor activity, accumulating evidence attributes anti-inflammatory effects to HHT, which have mainly been studied in leukocytes to date. However, a potential influence of HHT on inflammatory activation processes in endothelial cells, which are a key feature of inflammation and a prerequisite for the leukocyte-endothelial cell interaction and leukocyte extravasation, remains poorly understood. In this study, the anti-inflammatory potential of HHT and its derivative harringtonine (HT) on the TNF-induced leukocyte-endothelial cell interaction was assessed, and the underlying mechanistic basis of these effects was elucidated. HHT affected inflammation in vivo in a murine peritonitis model by reducing leukocyte infiltration and proinflammatory cytokine expression as well as ameliorating abdominal pain behavior. In vitro, HT and HHT impaired the leukocyte-endothelial cell interaction by decreasing the expression of the endothelial cell adhesion molecules intracellular adhesion molecule -1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This effect was mediated by a bipartite mechanism. While HHT did not affect the prominent TNF-induced pro-inflammatory NF-ĸB signaling cascade, the compound downregulated the VCAM1 mRNA expression in an IRF-1-dependent manner and diminished active ICAM1 mRNA translation as determined by polysome profiling. This study highlights HHT as an anti-inflammatory compound that efficiently hampers the leukocyte-endothelial cell interaction by targeting endothelial activation processes.

Improved Cell Adhesion on Self-Assembled Chiral Nematic Cellulose Nanocrystal Films.

Chirality is ubiquitous in nature, and closely related to biological phenomena. Nature-originated nanomaterials such as cellulose nanocrystals (CNCs) are able to self-assemble into hierarchical chiral nematic CNC films and impart handedness to nano and micro scale. However, the effects of the chiral nematic surfaces on cell adhesion are still unknown. Herein, this work presents evidence that the left-handed self-assembled chiral nematic CNC films (L-CNC) significantly improve the adhesion of L929 fibroblasts compared to randomly arranged isotropic CNC films (I-CNC). The fluidic force microscopy-based single-cell force spectroscopy is introduced to assess the cell adhesion forces on the substrates of L-CNC and I-CNC, respectively. With this method, a maximum adhesion force of 133.2 nN is quantified for mature L929 fibroblasts after culturing for 24 h on L-CNC, whereas the L929 fibroblasts exert a maximum adhesion force of 78.4 nN on I-CNC under the same condition. Moreover, the instant SCFS reveals that the integrin pathways are involved in sensing the chirality of substrate surfaces. Overall, this work offers a starting point for the regulation of cell adhesion via the self-assembled nano and micro architecture of chiral nematic CNC films, with potential practical applications in tissue engineering and regenerative medicine.

Dynamic Regulation of Cell Mechanotransduction through Sequentially Controlled Mobile Surfaces.

The physical properties of nanoscale cell-extracellular matrix (ECM) ligands profoundly impact biological processes, such as adhesion, motility, and differentiation. While the mechanoresponse of cells to static ligands is well-studied, the effect of dynamic ligand presentation with "adaptive" properties on cell mechanotransduction remains less understood. Utilizing a controllable diffusible ligand interface, we demonstrated that cells on surfaces with rapid ligand mobility could recruit ligands through activating integrin α5ß1, leading to faster focal adhesion growth and spreading at the early adhesion stage. By leveraging UV-light-sensitive anchor molecules to trigger a "dynamic to static" transformation of ligands, we sequentially activated α5ß1 and αvß3 integrins, significantly promoting osteogenic differentiation of mesenchymal stem cells. This study illustrates how manipulating molecular dynamics can directly influence stem cell fate, suggesting the potential of "sequentially" controlled mobile surfaces as adaptable platforms for engineering smart biomaterial coatings.

Iron Nano Biocomposite-Infused Biopolymeric Films: A Multifunctional Approach for Robust Skin Repair.

Sodium alginate (SA) biopolymeric films have various limitations such as poor mechanical properties, high vapor permeability, lack of antibacterial activity, excessive burst release, and weak cell adhesion. To overcome these limitations, a strategy involving the integration of nanofillers into an SA film matrix is explored. In this context, a cost-effective iron-containing carbon nano biocomposite (FeCNB) nanofiller is developed using a solvent-free technique. This nanocomposite is successfully incorporated into the alginate film matrix at varying concentrations (0.05, 0.1, and 0.15%) aimed at enhancing its physicochemical and biological properties for biomedical applications. Characterization through FESEM and BET analyses confirms the porous nature of the FeCNB. EDX shows the FeCNB's uniform distribution upon its integration into the film matrix, albeit without strong chemical interaction with SA. Instead, hydrogen bonding interactions become apparent in the FTIR spectra. By incorporating the FeCNB, the mechanical attributes of the films are improved and the water vapor permeability approaches the desired range (2000-2500 g/m2day). The film's swelling ratio reduction contributes to a decrease in water permeability. The antibacterial activity and sustained release property of the FeCNB-incorporated film are established using tetracycline hydrochloride (TCl), a model drug. The drug release profile resembled Korsmeyer-Peppas's release pattern. In vitro assessments via the MTT assay and scratch assay on NIH-3T3 cells reveal that FeCNB has no adverse effects on the biocompatibility of alginate films. The cell proliferation and adhesion to the SA film are significantly enhanced after infusion of the FeCNB. The in vivo study performed on the rat model demonstrates improved wound healing by FeCNB-impregnated films. Based on the comprehensive findings, the proposed FeCNB-incorporated alginate films prove to be a promising candidate for robust skin repair.

The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.

PTPRK is a receptor tyrosine phosphatase linked to the regulation of growth factor signalling and tumour suppression. It is stabilized at the plasma membrane by trans homophilic interactions upon cell-cell contact. It regulates cell-cell adhesion, but is also reported to regulate numerous cancer-associated signalling pathways. However, its signalling mechanism remains to be determined. Here, we find that PTPRK regulates cell adhesion signalling, suppresses invasion and promotes collective, directed migration in colorectal cancer cells. In vivo, PTPRK supports recovery from inflammation-induced colitis. In addition, we confirm that PTPRK functions as a tumour suppressor in the mouse colon and in colorectal cancer xenografts. PTPRK regulates growth factor and adhesion signalling, and suppresses epithelial to mesenchymal transition (EMT). Contrary to the prevailing notion that PTPRK directly dephosphorylates EGFR, we find that PTPRK regulation of both EGFR and EMT is independent of its catalytic function. This suggests that additional adaptor and scaffold functions are important features of PTPRK signalling.

Deletion of Talin1 in Myeloid Cells Facilitates Atherosclerosis in Mice.

BACKGROUND: Integrin-regulated monocyte recruitment and cellular responses of monocyte-derived macrophages are critical for the pathogenesis of atherosclerosis. In the canonical model, talin1 controls ligand binding to integrins, a prerequisite for integrins to mediate leukocyte recruitment and induce immune responses. However, the role of talin1 in the development of atherosclerosis has not been studied. Our study investigated how talin1 in myeloid cells regulates the progression of atherosclerosis. METHODS: On an Apoe-/- background, myeloid talin1-deficient mice and the control mice were fed with a high-fat diet for 8 or 12 weeks to induce atherosclerosis. The atherosclerosis development in the aorta and monocyte recruitment into atherosclerotic lesions were analyzed. RESULTS: Myeloid talin1 deletion facilitated the formation of atherosclerotic lesions and macrophage deposition in lesions. Talin1 deletion abolished integrin ß2-mediated adhesion of monocytes but did not impair integrin α4ß1-dependent cell adhesion in a flow adhesion assay. Strikingly, talin1 deletion did not prevent Mn2+- or chemokine-induced activation of integrin α4ß1 to the high-affinity state for ligands. In an in vivo competitive homing assay, monocyte infiltration into inflamed tissues was prohibited by antibodies to integrin α4ß1 but was not affected by talin1 deletion or antibodies to integrin ß2. Furthermore, quantitative polymerase chain reaction and ELISA analysis showed that macrophages produced cytokines to promote inflammation and the proliferation of smooth muscle cells. Ligand binding to integrin ß3 inhibited cytokine generation in macrophages, although talin1 deletion abolished the negative effects of integrin ß3. CONCLUSIONS: Integrin α4ß1 controls monocyte recruitment during atherosclerosis. Talin1 is dispensable for integrin α4ß1 activation to the high-affinity state and integrin α4ß1-mediated monocyte recruitment. Yet, talin1 is required for integrin ß3 to inhibit the production of inflammatory cytokines in macrophages. Thus, intact monocyte recruitment and elevated inflammatory responses cause enhanced atherosclerosis in talin1-deficient mice. Our study provides novel insights into the roles of myeloid talin1 and integrins in the progression of atherosclerosis.

Integration of transcriptomics and spatial biology analyses reveals Galactomyces ferment filtrate promotes epidermal interconnectivity via induction of keratinocyte differentiation, proliferation and cellular bioenergetics.

OBJECTIVE: Human skin is the first line of defence from environmental factors such as solar radiation and is susceptible to premature ageing, including a disruption in epidermal differentiation and homeostasis. We evaluated the impact of a Galactomyces Ferment Filtrate (GFF) on epidermal differentiation and response to oxidative stress. METHODS: We used transcriptomics, both spatial and traditional, to assess the impact of GFF on epidermal biology and homeostasis in keratinocytes (primary or immortalized) and in ex vivo skin explant tissue. The effect of GFF on cell adhesion rates, cellular ATP levels and proliferation rates were quantitated. Oxidative phosphorylation and glycolytic rates were measured under normal and stress-induced conditions. RESULTS: Transcriptomics from keratinocytes and ex vivo skin explants from multiple donors show GFF induces keratinocyte differentiation, skin barrier development and cell adhesion while simultaneously repressing cellular stress and inflammatory related processes. Spatial transcriptomics profiling of ex vivo skin indicated basal keratinocytes at the epidermal-dermal junction and cornifying keratinocytes in the top layer of the epidermis as the primary cell types influenced by GFF treatment. Additionally, GFF significantly increases crosstalk between suprabasal and basal keratinocytes. To support these findings, we show that GFF can significantly increase cell adhesion and proliferation in keratinocytes. GFF also protected overall cellular bioenergetics under metabolic or oxidative stress conditions. CONCLUSION: Our findings provide novel insights into cellular differences and epidermal spatial localization in response to GFF, supporting previous findings that this filtrate has a significant impact on epidermal biology and homeostasis, particularly on spatially defined crosstalk. We propose that GFF can help maintain epidermal health by enhancing keratinocyte crosstalk and differentiation/proliferation balance as well as promoting an enhanced response to stress.

Strontium-doped bioactive glass-functionalized polyetheretherketone enhances osseointegration by facilitating cell adhesion.

In the field of orthopedics, surgeons have long been facing the challenge of loosening of external fixation screws due to inherent material characteristics. Despite Polyetheretherketone (PEEK) being employed as an orthopedic implant material for many years, its bio-inert nature often hinders bone healing due to the limited bioactivity, which restricts its clinical applications. Herein, a new type of orthopedic implant (Sr-SPK) was developed by introducing strontium (Sr)-doped mesoporous bioactive glass (Sr-MBG) onto the surface of PEEK implants through a simple and feasible method. In vitro experiments revealed that Sr-SPK effectively promotes osteogenic differentiation while concurrently suppressing the formation of osteoclasts. The same results were validated in vivo with Sr-SPK significantly improving bone integration. Upon investigation, it was found that Sr-SPK promotes adhesion among bone marrow mesenchymal stem cells (BMSCs) thereby promoting osteogenesis by activating the regulation of actin cytoskeletal and focal adhesion pathways, as identified via transcriptome analysis. In essence, these findings suggest that the newly constructed Sr-doped biofunctionalized PEEK implant developed in this research can promote osteoblast differentiation and suppress osteoclast activity by enhancing cell adhesion processes. These results underline the immense potential of such an implant for wide-ranging clinical applications in orthopedics.

Conditions that promote transcellular neutrophil migration in vivo.

Circulating leukocytes enter tissue either through endothelial junctions (paracellular) or via a pore through the body of endothelial cells (transcellular). We have previously shown that genetically replacing VE-cadherin with a VE-cadherin-α-catenin (VEC-αC) fusion construct-which binds constitutively to actin-obstructs junctions, and blocks leukocyte extravasation in lung, skin and postcapillary venules of cremaster muscle. However, neutrophil recruitment into the inflamed peritoneal cavity was unimpaired. Investigating reasons for this, here, we visualized neutrophil diapedesis by 3D intravital video microscopy in the cremaster muscle and omentum, the major site of neutrophil recruitment into the peritoneal cavity. We found that 80% of neutrophil-extravasation occurred through HEVs in the omentum, which was unimpaired by VEC-αC. In addition, in larger venules (60-85 µm) of both tissues, less than 15% of neutrophils extravasated transcellularly in WT mice. However, in VEC-α-C mice, transcellular diapedesis increased severalfold in the omentum, but not in the cremaster. In line with this, omental venules expressed higher levels of ICAM-1 and atypical chemokine receptor 1. Furthermore, only in the omentum, VEC-αC expression caused reduced elongation of venular endothelium in flow-direction, suggesting different biomechanical properties. Collectively, VEC-αC does not inhibit paracellular transmigration in all types of venules and can modulate the diapedesis route.

NMR Studies of the Interactions between Sialyllactoses and the Polysialytransferase Domain for Polysialylation Inhibition.

It is known that sialyllactose (SL) in mammalians is a major source of sialic acid (Sia), which can further form cytidine monophosphate sialic acid (CMP-Sia), and the final product is polysialic acid (polySia) using polysialyltransferases (polySTs) on the neural cell adhesion molecule (NCAM). This process is called NCAM polysialylation. The overexpression of polysialylation is strongly related to cancer cell migration, invasion, and metastasis. In order to inhibit the overexpression of polysialylation, in this study, SL was selected as an inhibitor to test whether polysialylation could be inhibited. Our results suggest that the interactions between the polysialyltransferase domain (PSTD) in polyST and CMP-Siaand the PSTD and polySia could be inhibited when the 3'-sialyllactose (3'-SL) or 6'-sialyllactose (6'-SL) concentration is about 0.5 mM or 6'-SL and 3 mM, respectively. The results also show that SLs (particularly for 3'-SL) are the ideal inhibitors compared with another two inhibitors, low-molecular-weight heparin (LMWH) and cytidine monophosphate (CMP), because 3'-SL can not only be used to inhibit NCAM polysialylation, but is also one of the best supplements for infant formula and the gut health system.

Osteogenic Differentiation Potential of iMSCs on GelMA-BG-MWCNT Nanocomposite Hydrogels.

The ability of bone biomaterials to promote osteogenic differentiation is crucial for the repair and regeneration of osseous tissue. The development of a temporary bone substitute is of major importance in enhancing the growth and differentiation of human-derived stem cells into an osteogenic lineage. In this study, nanocomposite hydrogels composed of gelatin methacryloyl (GelMA), bioactive glass (BG), and multiwall carbon nanotubes (MWCNT) were developed to create a bone biomaterial that mimics the structural and electrically conductive nature of bone that can promote the differentiation of human-derived stem cells. GelMA-BG-MWCNT nanocomposite hydrogels supported mesenchymal stem cells derived from human induced pluripotent stem cells, hereinafter named iMSCs. Cell adhesion was improved upon coating nanocomposite hydrogels with fibronectin and was further enhanced when seeding pre-differentiated iMSCs. Osteogenic differentiation and mature mineralization were promoted in GelMA-BG-MWCNT nanocomposite hydrogels and were most evidently observed in the 70-30-2 hydrogels, which could be due to the stiff topography characteristic from the addition of MWCNT. Overall, the results of this study showed that GelMA-BG-MWCNT nanocomposite hydrogels coated with fibronectin possessed a favorable environment in which pre-differentiated iMSCs could better attach, proliferate, and further mature into an osteogenic lineage, which was crucial for the repair and regeneration of bone.

Characterization of Novel Cell-Adhesive Peptides for Biomaterial Development.

In previous studies, my group developed cell-adhesive peptide-polysaccharide complexes as biomaterials for tissue engineering. Having a wide variety of cell-adhesive peptides is important as the biological functions of peptide-polysaccharide complexes are highly dependent on the biological activity of peptides. This paper reviews the biological activities of two types of recently characterized cell-adhesive peptides. The first is peptides rich in basic amino acids originating from octaarginine. We analyzed the relationships between the amino acid composition of basic peptides and cell adhesion, elongation, and proliferation and identified the most suitable peptide for cell culture. The second was arginine-glycine-aspartic acid (RGD)-containing peptides that promote the adhesion of induced pluripotent stem cells (iPSCs). We identified the RGD-surrounding sequences necessary for iPSC adhesion, clarified the underlying mechanism, and improved cell adhesion by modifying the structure-activity relationships. The novel cell-adhesive peptides identified in our previous studies may aid in the development of novel peptide-based biomaterials.

Cell adhesion molecule CD44 is dispensable for reactive astrocyte activation during prion disease.

Prion diseases are fatal, infectious, neurodegenerative disorders resulting from accumulation of misfolded cellular prion protein in the brain. Early pathological changes during CNS prion disease also include reactive astrocyte activation with increased CD44 expression, microgliosis, as well as loss of dendritic spines and synapses. CD44 is a multifunctional cell surface adhesion and signalling molecule which is considered to play roles in astrocyte morphology and the maintenance of dendritic spine integrity and synaptic plasticity. However, the role of CD44 in prion disease was unknown. Here we used mice deficient in CD44 to determine the role of CD44 during prion disease. We show that CD44-deficient mice displayed no difference in their response to CNS prion infection when compared to wild type mice. Furthermore, the reactive astrocyte activation and microgliosis that accompanies CNS prion infection was unimpaired in the absence of CD44. Together, our data show that although CD44 expression is upregulated in reactive astrocytes during CNS prion disease, it is dispensable for astrocyte and microglial activation and the development of prion neuropathogenesis.