Remineralization Potential of a Novel Biomimetic Material (Self-assembling Peptide P11-4) on Early Enamel Caries: An In Vitro Study.

AIM: To assess the remineralizing potential of self-assembling peptide P11-4 and compare it to the remineralizing potential of fluoride varnish using DIAGNOdentTM, as well as the amount of mineral gain after application of fluoride varnish and self-assembling peptide P11-4. MATERIALS AND METHODS: This study included 20 premolars extracted during orthodontic therapy with all surfaces intact and free of hypoplastic regions, white spot lesions (WSL) and dental caries. The teeth sample for Curodont RepairTM (self-assembling P11-4) and Bifluorid 10® (fluoride varnish) was equally divided. On each tooth surface, a 2 × 2 mm window was created. The samples were immersed in a demineralizing solution for 96 hours before being subjected to DIAGNOdentTM pen reading, ICDAS-II scoring, and scanning electron microscopy-energy-dispersive X-ray (SEM-EDX) analysis on one half of the sample. The remineralizing agents were applied to the second half of the sample according to the manufacturer's instructions and placed in artificial saliva for 21 days, with the artificial salvia being replaced every 24 hours. After 21 days, the second half of the sample was subjected to DIAGNOdentTM pen reading, ICDAS-II score, and SEM-EDX analysis. RESULTS: Following remineralization, the DIAGNOdentTM pen and ICDAS-II score values differed statistically between the two groups, with the Bifluorid 10® group reporting higher mean values (p > 0.05) using t-test analysis. Energy-dispersive X-ray analysis using the t-test revealed a statistically significant result for remineralization (p < 0.05), with CurodontTM Repair group (55.150.84) reporting better mean values than Bifluorid 10® for phosphorus and calcium, but Bifluorid 10® reporting a higher result in remineralization (p < 0.05) than CurodontTM Repair for fluoride. CONCLUSION: CurodontTM Repair showed better remineralizing potential compared with Bifluorid 10® varnish. In terms of the mineral gain, CurodontTM Repair showed better results for calcium and phosphorus post-remineralization. Whereas Bifluorid 10® showed a higher gain in terms of fluoride. Self-assembling peptide P11-4 can be used as an alternative to fluoride varnish for remineralizing WSL. CLINICAL SIGNIFICANCE: Self-assembling polypeptide P11-4 is a novel remineralizing agent for initial enamel lesions, which is the least-invasive method of enamel remineralization.

A Natural Alternative Treatment for Urinary Tract Infections: Itxasol©, the Importance of the Formulation.

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.

2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy.

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS2 doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2 and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS2 (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2 in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.

Enzyme/Nanocopper Hybrid Nanozymes: Modulating Enzyme-like Activity by the Protein Structure for Biosensing and Tumor Catalytic Therapy.

Artificial enzymes with modulated enzyme-mimicking activities of natural systems represent a challenge in catalytic applications. Here, we show the creation of artificial Cu metalloenzymes based on the generation of Cu nanoparticles in an enzyme matrix. Different enzymes were used, and the structural differences between the enzymes especially influenced the controlled the size of the nanoparticles and the environment that surrounds them. Herein, we demonstrated that the oxidase-like catalytic activity of these copper nanozymes was rationally modulated by enzyme used as a scaffold, with a special role in the nanoparticle size and their environment. In this sense, these nanocopper hybrids have confirmed the ability to mimic a unique enzymatic activity completely different from the natural activity of the enzyme used as a scaffold, such as tyrosinase-like activity or as Fenton catalyst, which has extremely higher stability than natural mushroom tyrosinase. More interestingly, the oxidoreductase-like activity of nanocopper hybrids was cooperatively modulated with the synergistic effect between the enzyme and the nanoparticles improving the catalase activity (no peroxidase activity). Additionally, a novel dual (metallic and enzymatic activity) of the nanozyme made the highly improved catechol-like activity interesting for the design of 3,4-dihydroxy-l-phenylalanine (l-DOPA) biosensor for detection of tyrosinase. These hybrids also showed cytotoxic activity against different tumor cells, interesting in biocatalytic tumor therapy.

3D Cell Printing of Tissue/Organ-Mimicking Constructs for Therapeutic and Drug Testing Applications.

The development of artificial tissue/organs with the functional maturity of their native equivalents is one of the long-awaited panaceas for the medical and pharmaceutical industries. Advanced 3D cell-printing technology and various functional bioinks are promising technologies in the field of tissue engineering that have enabled the fabrication of complex 3D living tissue/organs. Various requirements for these tissues, including a complex and large-volume structure, tissue-specific microenvironments, and functional vasculatures, have been addressed to develop engineered tissue/organs with native relevance. Functional tissue/organ constructs have been developed that satisfy such criteria and may facilitate both in vivo replenishment of damaged tissue and the development of reliable in vitro testing platforms for drug development. This review describes key developments in technologies and materials for engineering 3D cell-printed constructs for therapeutic and drug testing applications.

Cancer Cell Membrane Camouflaged Semi-Yolk@Spiky-Shell Nanomotor for Enhanced Cell Adhesion and Synergistic Therapy.

Cell adhesion of nanosystems is significant for efficient cellular uptake and drug delivery in cancer therapy. Herein, a near-infrared (NIR) light-driven biomimetic nanomotor is reported to achieve the improved cell adhesion and cellular uptake for synergistic photothermal and chemotherapy of breast cancer. The nanomotor is composed of carbon@silica (C@SiO2 ) with semi-yolk@spiky-shell structure, loaded with the anticancer drug doxorubicin (DOX) and camouflaged with MCF-7 breast cancer cell membrane (i.e., mC@SiO2 @DOX). Such biomimetic mC@SiO2 @DOX nanomotors display efficient self-thermophoretic propulsion due to a thermal gradient generated by asymmetrically spatial distribution. Moreover, the MCF-7 cancer cell membrane coating can remarkably reduce the bioadhesion of nanomotors in biological medium and exhibit highly specific self-recognition of the source cell line. The combination of effective propulsion and homologous targeting dramatically improves cell adhesion and the resultant cellular uptake efficiency in vitro from 26.2% to 67.5%. Therefore, the biomimetic mC@SiO2 @DOX displays excellent synergistic photothermal and chemotherapy with over 91% MCF-7 cell growth inhibition rate. Such smart design of the fuel-free, NIR light-powered biomimetic nanomotor may pave the way for the application of self-propelled nanomotors in biomedicine.

Advances in next-generation lipid-polymer hybrid nanocarriers with emphasis on polymer-modified functional liposomes and cell-based-biomimetic nanocarriers for active ingredients and fractions from Chinese medicine delivery.

Recently, functional liposomes modified with versatile polymer and cell-based- biomimetic nanoparticles have emerged as the most advanced lipid-polymer hybrid nanocarriers (LPNs) for drug delivery. This review highlights the advances of these two LPNs in the delivery of active ingredients and fractions from Chinese medicine with promising therapeutic, chemopreventive, or chemosensitive effects. To understand their complete potency, the relationship between the nanoparticle characteristics and their in vitro and in vivo performance characteristics has been discussed. Polymer-modified liposomes and cell-based biomimetic nanoparticles are beneficial for improving absorption, modulating release, targeting and overcoming multidrug resistance, and reducing side effects. The associated challenges, current limitations, and opportunities in this field are also discussed.

Encapsulation of collagen mimetic peptide-tethered vancomycin liposomes in collagen-based scaffolds for infection control in wounds.

Wound infections are a significant clinical problem affecting millions of people worldwide. Topically applied antibacterial formulations with longer residence time and controlled antimicrobial release would offer significant benefits for improved prevention and treatment of infected wounds. In this study, we developed collagen mimetic peptide (CMP) tethered vancomycin (Van)-containing liposomes (Lipo) (CMP-Van-Lipo) hybridized to collagen-based hydrogels ('co-gels,' e.g., collagen/fibrin combination hydrogels) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in vitro and in vivo. Tethering CMP-Van-Lipo nanostructures to co-gels enabled sustained Van release and enhanced in vitro antibacterial effects against MRSA as compared to Van loaded co-gels or Van-Lipo loaded co-gels following multiple fresh bacterial inoculations over a period of 48 h. These results were successfully translated in vivo wherein MRSA infected wounds were effectively treated with CMP-Van-Lipo loaded co-gels for up to 9 days, whereas the activity of Van loaded co-gels and Van-Lipo loaded co-gels were limited to <2 days. Moreover, CMP-Van-Lipo retained in vivo antibacterial activity even after re-inoculation with bacteria; however, Van loaded co-gels and Van-Lipo loaded co-gels allowed significant bacterial growth demonstrating their limited efficacy. Altogether, these results provide proof-of-concept that CMP-Van-Lipo loaded co-gels can be effective topical formulations for preventive treatment of MRSA wound infections. STATEMENT OF SIGNIFICANCE: Current topical antimicrobial formulations (e.g., creams, gels, and ointments) do not control release, leaving antimicrobial concentrations either too high or too low at different time points, and provoking the development of antibacterial resistance and recurrence of wound infections. Here, collagen mimetic peptides (CMPs) were used to stably hybridize vancomycin-containing liposomal nanocarriers (CMP-Van-Lipo) within collagen-fibrin co-gels via triple-helical integration with collagen, enabling control over Van release for prolonged time periods and minimizing the adverse effects of the Lipo formulations on fibroblast cell viability in the wound bed. The CMP-Van-Lipo loaded co-gel's higher antibacterial effects in vitro were successfully translated in vivo for treatment of MRSA-infected mouse wounds, and thus the co-gels can be a potentially translatable treatment for improved clinical wound management.

Chinese sesame stick-inspired nano-fibrous scaffolds for tumor therapy and skin tissue reconstruction.

Surgery is a common treatment to remove the solid skin tumors. It is of great importance to eliminate the remaining tumor cells and achieve the simultaneous tissue reconstruction after surgery for improving life quality of cancer patients. Inspired by the designing strategy and fabrication method of Chinese sesame sticks, a Chinese sesame stick-like scaffold is developed by spin coating of CaCuSi4O10 nanoparticles (NPs) on the surface of electrospun fibers for tumor therapy and skin tissue reconstruction. The CaCuSi4O10 NPs can transform near-infrared light energy into heat energy, showing the photothermal conversion efficiency of 33.8%. After coating of the CaCuSi4O10 NPs on the fibers, the prepared scaffolds exhibit the Chinese sesame stick-like structure and achieve bifunction with both tumor killing and skin tissue reconstruction capacities. The CaCuSi4O10 NPs endow the scaffolds with photothermal ablation potential to rapidly kill the in vitro tumor cells. Furthermore, Chinese sesame stick-like scaffolds effectively inhibit in vivo tumor growth at the early stage and accelerate healing of cancer surgery-caused wounds at the later stage in tumor-bearing mice. Additionally, the composite scaffolds promote chronic wound healing by stimulating in vivo angiogenesis and re-epithelization, harnessing locally release of bioactive Cu2+ and SiO44- ions from the CaCuSi4O10 NPs. Therefore, the Chinese sesame stick-inspired scaffolds may lay a solid foundation for clinical treatment of cancers and cancer surgery-induced tissue damage.

Targeting mitochondrial dysfunction and oxidative stress in heart failure: Challenges and opportunities.

Mitochondrial dysfunction characterized by impaired bioenergetics, oxidative stress and aldehydic load is a hallmark of heart failure. Recently, different research groups have provided evidence that selective activation of mitochondrial detoxifying systems that counteract excessive accumulation of ROS, RNS and reactive aldehydes is sufficient to stop cardiac degeneration upon chronic stress, such as heart failure. Therefore, pharmacological and non-pharmacological approaches targeting mitochondria detoxification may play a critical role in the prevention or treatment of heart failure. In this review we discuss the most recent findings on the central role of mitochondrial dysfunction, oxidative stress and aldehydic load in heart failure, highlighting the most recent preclinical and clinical studies using mitochondria-targeted molecules and exercise training as effective tools against heart failure.

Promising Biomolecules.

The osteochondral defect (OD) comprises the articular cartilage and its subchondral bone. The treatment of these lesions remains as one of the most problematic clinical issues, since these defects include different tissues, requiring distinct healing approaches. Among the growing applications of regenerative medicine, clinical articular cartilage repair has been used for two decades, and it is an effective example of translational medicine; one of the most used cell-based repair strategies includes implantation of autologous cells in degradable scaffolds such as alginate, agarose, collagen, chitosan, chondroitin sulfate, cellulose, silk fibroin, hyaluronic acid, and gelatin, among others. Concerning the repair of osteochondral defects, tissue engineering and regenerative medicine started to design single- or bi-phased scaffold constructs, often containing hydroxyapatite-collagen composites, usually used as a bone substitute. Biomolecules such as natural and synthetic have been explored to recreate the cartilage-bone interface through multilayered biomimetic scaffolds. In this chapter, a succinct description about the most relevant natural and synthetic biomolecules used on cartilage and bone repair, describing the procedures to obtain these biomolecules, their chemical structure, common modifications to improve its characteristics, and also their application in the biomedical fields, is given.

Enhanced photothermal therapy of biomimetic polypyrrole nanoparticles through improving blood flow perfusion.

In this study, we reported a strategy to improve delivery efficiency of a long-circulation biomimetic photothermal nanoagent for enhanced photothermal therapy through selectively dilating tumor vasculature. By using a simply nanocoating technology, a biomimetic layer of natural red blood cell (RBC) membranes was camouflaged on the surface of photothermal polypyrrole nanoparticles (PPy@RBC NPs). The erythrocyte-mimicking PPy NPs inherited the immune evasion ability from natural RBC resulting in superior prolonged blood retention time. Additionally, excellent photothermal and photoacoustic imaging functionalities were all retained attributing to PPy NPs cores. To further improve the photothermal outcome, the endothelin A (ETA) receptor antagonist BQ123 was jointly employed to regulate tumor microenvironment. The BQ123 could induce tumor vascular relaxation and increase blood flow perfusion through modulating an ET-1/ETA transduction pathway and blocking the ETA receptor, whereas the vessel perfusion of normal tissues was not altered. Through our well-designed tactic, the concentration of biomimetic PPy NPs in tumor site was significantly improved when administered systematically. The study documented that the antitumor efficiency of biomimetic PPy NPs combined with specific antagonist BQ123 was particularly prominent and was superior to biomimetic PPy NPs (P < 0.05) and PEGylated PPy NPs with BQ123 (P < 0.01), showing that the greatly enhanced photothermal treatment could be achieved with low-dose administration of photothermal agents. Our findings would provide a promising procedure for other similar enhanced photothermal treatment by blocking ETA receptor to dramatically increase the delivery of biomimetic photothermal nanomaterials.

A bispecific antibody mimicking factor VIII in hemophilia A therapy.

Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. The clinical phase 1 study designed to assess the pharmacokinetics, pharmacodynamics and safety of emicizumab has been initiated. Severe emicizumab-related adverse events were minimal. The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.

Current status and future prospects for biologic treatments of psoriasis.

INTRODUCTION: Biological agents have transformed psoriasis treatment by selectively targeting immune signaling molecules involved in psoriasis pathogenesis. While biologics offer the most effective treatment of moderate to severe psoriasis, they are not without complications. Some patients treated with biologics have poor clinical responses, form anti-drug antibodies, or develop adverse events. Additionally, there is growing need for head-to-head studies comparing biologic treatment regimens, efficacy, and safety. Areas covered: Here we review the literature surrounding biologics already in clinical use and those undergoing development and clinical trials. We also investigate the development and approval of small molecules inhibitors and biosimilars used to treat psoriasis. Expert commentary: As the psoriasis treatment armamentarium continues to expand, it is important to follow the safety profile of these drugs both in clinical trials and in post-marketing registries to ensure their long-term safety. Physicians must be aware of the limitations of existing safety data of a drug and the potential risk for rare adverse events when selecting appropriate treatments and monitoring patient outcomes.

The assessment of the effect of a cosmetic product brightening the skin of people with discolorations of different etiology.

BACKGROUND: Hyperpigmentations are disorders displayed with a change in the color of the skin, its strange shape, the lack of symmetry, and irregular placement. They appear no matter on the age, gender, and often as a congenital defect. Disorder connected with overproduction of melanin by pigmentary cells. The change of color is due to endogenous and exogenous cause. OBJECTIVES: The aim of this thesis was to conduct a research in vivo. This will allow to judge the effectiveness of the cosmetic product which brightens the skin with hyperpigmentation problems. The characteristics of dermocosmetics were tested on people with various etiology of hyperpigmentation. The aim of the research was to assess the effect of the active substances used daily on skin hyperpigmentation. METHODS: The tests were carried out on groups of patients with hyperpigmentations. The application of the pharmaceutical and the use of specific apparatus measurements were taken on every medical checkup. A survey was conducted to assess the changes in the face, neck, and neckline skin. The research was based on the apparatus analysis of the skin condition (MPA® , VISIA® ). RESULTS: Regular application of the pharmaceutical caused brightening of hyperpigmentations (P < 0.05). General improvement in skin condition was also observed - the increase in skin elasticity, smoothness, and the enhancement of hydration levels. CONCLUSIONS: Dermocosmetics for people with hyperpigmentation are an essential part of their medical treatment. In case of epidermal hyperpigmentation, the recipe of individually chosen and tested combination of ingredients enables us to reach satisfactory results.

Dental Pulp Cell Behavior in Biomimetic Environments.

There is emerging recognition of the importance of a physiologically relevant in vitro cell culture environment to promote maintenance of stem cells for tissue engineering and regenerative medicine purposes. In vivo, appropriate cellular cues are provided by local tissue extracellular matrix (ECM), and these are not currently recapitulated well in vitro using traditional cultureware. We therefore hypothesized that better replication of the in vivo environment for cell culture and differentiation could be achieved by culturing dental pulp cells with their associated ECM. Primary dental pulp cells were subsequently seeded onto pulp-derived ECM-coated cultureware. While at up to 24 h they exhibited the same level of adherence as those cells seeded on tissue culture-treated surfaces, by 4 d cell numbers and proliferation rates were significantly decreased in cells grown on pulp ECM compared with controls. Analysis of stem cell and differentiation marker transcripts, as well as Oct 3/4 protein distribution, supported the hypothesis that cells cultured on ECM better maintained a stem cell phenotype compared with those cultured on standard tissue culture-treated surfaces. Subsequent differentiation analysis of cells cultured on ECM demonstrated that they exhibited enhanced mineralization, as determined by alizarin red staining and mineralized marker expression. Supplementation of a 3% alginate hydrogel with pulp ECM components and dental pulp cells followed by differentiation induction in mineralization medium resulted in a time-dependent mineral deposition at the periphery of the construct, as demonstrated histologically and using micro-computed tomography analysis, which was reminiscent of tooth structure. In conclusion, data indicate that culture of pulp cells in the presence of ECM better replicates the in vivo environment, maintaining a stem cell phenotype suitable for downstream tissue engineering applications.

Effects of new biomimetic regenerating agents on corneal wound healing in an experimental model of post-surgical corneal ulcers.

OBJECTIVE: The purpose of this study is to assess the effectiveness of the topical application of cacicol regenerating agent (RGTA) in an experimental model of corneal ulcer after photorefractive keratectomy (PRK) in mice. METHODS: Mice were subjected to PRK surgery with a 2.0mm ablation zone on the central cornea and 45mm of depth on a VISX Star S2 excimer laser. Corneas were treated topically with cacicol drops 1hour and 48hours after injury. Control groups received balanced salt solution (BSS) in the same dosage. Clinical and histopathological events were evaluated at 1, 2, 3 and 7 days after surgery. Sections obtained through the central region of the corneas were used to analyze the histopathological events of injured and healed corneas. αSMA (myofibroblast transformation), E cadherin (assembly of epithelial cells) and neuronal class III ß-tubulin (innervation) were performed. RESULTS: Corneas treated topically with cacicol for 7 days showed a greater degree of transparency compared to controls. cacicol treated corneas showed improved epithelial cytoarchitecture. Analysis of αSMA profiles in the stroma showed that cacicol reduced or delayed the presence of myofibroblasts in the stroma compared to BSS (P<0.001). Finally, a putative neuroregenerative effect of cacicol was found in corneas subjected to an experimental PRK lesion. In some cases some interindividual variability could be observed due to the design of the experimental model. This is a limitation to consider, despite the statistical significance of the data. CONCLUSIONS: In a model of laser induced surgical lesions in the cornea, topical application of an RGTA (i.e. cacicol) could be involved in avoiding myofibroblast scarring formation and promoting nerve regeneration.

A multi-channel biomimetic neuroprosthesis to support treadmill gait training in stroke patients.

This study presents an innovative multi-channel neuroprosthesis that induces a biomimetic activation of the main lower-limb muscles during treadmill gait training to be used in the rehabilitation of stroke patients. The electrostimulation strategy replicates the physiological muscle synergies used by healthy subjects to walk on a treadmill at their self-selected speed. This strategy is mapped to the current gait sub-phases, which are identified in real time by a custom algorithm. This algorithm divides the gait cycle into six sub-phases, based on two inertial sensors placed laterally on the shanks. Therefore, the pre-defined stimulation profiles are expanded or stretched based on the actual gait pattern of each single subject. A preliminary experimental protocol, involving 10 healthy volunteers, was carried out to extract the muscle synergies and validate the gait-detection algorithm, which were afterwards used in the development of the neuroprosthesis. The feasibility of the neuroprosthesis was tested on one healthy subject who simulated different gait patterns, and a chronic stroke patient. The results showed the correct functioning of the system. A pilot study of the neurorehabilitation treatment for stroke patients is currently being carried out.

Recognition of antigen-specific B-cell receptors from chronic lymphocytic leukemia patients by synthetic antigen surrogates.

In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of antigen surrogates.

Effects of 45S5 bioglass on surface properties of dental enamel subjected to 35% hydrogen peroxide.

Tooth bleaching agents may weaken the tooth structure. Therefore, it is important to minimize any risks of tooth hard tissue damage caused by bleaching agents. The aim of this study was to evaluate the effects of applying 45S5 bioglass (BG) before, after, and during 35% hydrogen peroxide (HP) bleaching on whitening efficacy, physicochemical properties and microstructures of bovine enamel. Seventy-two bovine enamel blocks were prepared and randomly divided into six groups: distilled deionized water (DDW), BG, HP, BG before HP, BG after HP and BG during HP. Colorimetric and microhardness tests were performed before and after the treatment procedure. Representative specimens from each group were selected for morphology investigation after the final tests. A significant color change was observed in group HP, BG before HP, BG after HP and BG during HP. The microhardness loss was in the following order: group HP>BG before HP, BG after HP>BG during HP>DDW, BG. The most obvious morphological alteration of was observed on enamel surfaces in group HP, and a slight morphological alteration was also detected in group BG before HP and BG after HP. Our findings suggest that the combination use of BG and HP could not impede the tooth whitening efficacy. Using BG during HP brought better protective effect than pre/post-bleaching use of BG, as it could more effectively reduce the mineral loss as well as retain the surface integrity of enamel. BG may serve as a promising biomimetic adjunct for bleaching therapy to prevent/restore the enamel damage induced by bleaching agents.