Effect of Nanoparticle Curvature on Its Interaction with Serum Proteins.

The size or the curvature of nanoparticles (NPs) plays an important role in regulating the composition of the protein corona. However, the molecular mechanisms of how curvature affects the interaction of NPs with serum proteins still remain elusive. In this study, we employ all-atom molecular dynamics simulations to investigate the interactions between two typical serum proteins and PEGylated Au NPs with three different surface curvatures (0, 0.1, and 0.5 nm-1, respectively). The results show that for proteins with a regular shape, the binding strength between the serum protein and Au NPs decreases with increasing curvature. For irregularly shaped proteins with noticeable grooves, the binding strength between the protein and Au NPs does not change obviously with increasing curvature in the cases of smaller curvature. However, as the curvature continues to increase, Au NPs may act as ligands firmly adsorbed in the protein grooves, significantly enhancing the binding strength. Overall, our findings suggest that the impact of NP curvature on protein adsorption may be nonmonotonic, which may provide useful guidelines for better design of functionalized NPs in biomedical applications.

Protective mechanisms of Taiwanese green propolis toward high glucose-induced inflammation via NLRP3 inflammasome signaling pathway in human gingival fibroblasts.

OBJECTIVE: To investigate protective effects of Taiwanese green propolis (TGP) against high glucose-induced inflammatory responses in human gingival fibroblasts (HGFs) through NLRP3 inflammasome signaling pathway. BACKGROUND: NLRP3 inflammasome has been implicated in the progression of both diabetes mellitus and periodontitis, suggesting a common potential therapeutic target for these diseases. Propolis is renowned for various biological activities, particularly anti-inflammation and antioxidant, representing a promising therapy for many conditions. However, underlying mechanisms remain unclear. METHODS: The cytotoxicity of TGP was evaluated by cell viability assay. The mRNA levels and protein expression or secretion of various inflammatory molecules and NLRP3 inflammasome-related molecules in high glucose-exposed HGFs with or without pretreatment of TGP (5 µg/ml) were determined by real-time PCR and western blot or specific kits, respectively. Intracellular and mitochondrial ROS measurements, NADPH oxidase activity determination, and subcellular fractions were performed to assess ROS generation. The transcriptional activity of NF-κB was measured by luciferase reporter kit. The signaling components were further differentiated using pharmacological inhibitors of ROS and small interfering RNAs of TLR2, TLR4, or NF-κB. RESULTS: High glucose could induce IL-1ß-driven inflammatory responses in HGFs via the activation of NLRP3 inflammasome regulated by TLR2/TLR4 coupled ROS in NF-κB-dependent manner. TGP had no adverse impact on the cell viability of HGFs at concentrations no greater than 10 µg/ml, and could exert inhibitory effects on high glucose-induced inflammatory responses via the interruption of NLRP3 inflammasome signaling pathway. CONCLUSION: Taiwanese green propolis could elicit protective effects against IL-1ß-driven inflammation in high glucose-exposed HGFs through TLR2/TLR4 combined ROS/NF-κB/NLRP3 inflammasome pathway.

Controlling the Interaction of Nanoparticles with Cell Membranes by the Polymeric Tether.

The well control over the cell-nanoparticle interaction can be of great importance and necessity for different biomedical applications. In this work, we propose a new and simple way (i.e., polymeric tether) to tuning the interaction between nanoparticles and cell membranes by dissipative particle dynamics simulations. It is found that the linked nanoparticles (via polymeric tether) can show some cooperation during the cellular uptake and thereby have a higher wrapping degree than the single nanoparticle. The effect of the property of the polymer on the wrapping is also investigated, and it is found that the length, rigidity, and hydrophobicity of the polymer play an important role. More interestingly, the uptake of linked nanoparticles could be adjusted to the firm adhesion via two rigid polymeric tethers. The present study may provide some useful guidelines for novel design of functional nanomaterials in the experiments.

Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer's disease.

Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs-treated cells were found to restore gradually with re-elongation of retracted dendrites. Meanwhile, Cell Counting Kit-8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs-treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α-tubulin and F-actin demonstrated that the hDPSCs-treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD.

Improving corrosion resistance and biocompatibility of AZ31 magnesium alloy by ultrasonic cold forging and micro-arc oxidation.

Corrosion resistant and biocompatible AZ31 magnesium alloy surfaces were successfully prepared by ultrasonic cold forging and subsequent micro-arc oxidation. The properties of these ultrasonic cold forging pretreated (UCFT)AZ31 magnesium alloy surfaces containing Sr-Ca-P micro-arc oxide coating (MAO/UCFT/AZ31) were studied. Results showed that surface grain refinement of AZ31 Mg alloy in the depth of 400 µm owing to the ultrasonic cold forging pretreatment was verified, and which provides more discharge channels for subsequent micro-arc oxidation. Comparing with the AZ31 magnesium alloy (AZ31) and ultrasonic cold forging technology treated AZ31 magnesium alloy samples (UCFT/AZ31), the corrosion resistance of MAO/UCFT/AZ31 significantly improved, which is also supported by the immersion experiments and electrochemical tests in simulated body fluid. Meanwhile, the MAO/UCFT/AZ31 samples also had excellent cytocompatibility as well as MAO/AZ31 samples. These results may beneficial to the developing of biodegradable medical materials in future.

A combined-modification method of carboxymethyl ß-cyclodextrin and lignin for nano-hydroxyapatite to reinforce poly(lactide-co-glycolide) for bone materials.

Lignin is the second most abundant natural biomacromolecule. A new surface-modification for nano-hydroxyapatite (n-HA) by carboxymethyl ß-cyclodextrin (CM-ß-CD) and lignin and its reinforce effect for poly(lactide-co-glycolide) (PLGA) were investigated by Fourier transformation infrared (FTIR), X-ray diffraction pattern (XRD), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), dispersion images, the tensile tests, scanning electron microscope (SEM), differential scanning calorimeter (DSC) and polarized optical microscopy (POM), compared to the singled-modification of CM-ß-CD or lignin. The results showed that the appropriate combined-modified n-HA displayed excellent synergistic effects for increasing the dispersion, yielding good interfacial bonding between n-HA with PLGA matrix. The tensile strength of the composite was still 14.53% higher than that of PLGA, for a n-HA addition amount of 15 wt%, which was significantly better than that for the singled-modified n-HA. Additionally, in vitro degradation behavior was evaluated by soaking in simulated body fluid (SBF), and their cell response was carried out by interaction tests with bone mesenchymal stem cells. The results indicated that the combined-modification method promoted good degradation behavior and apatite deposition, as well as excellent cell biocompatibility. This study may offer an important guidance to obtain PLGA-based composites reinforced by surface-modified n-HA as bone materials.

Hydrothermal liquefaction of cellulose in ammonia/water.

In order to obtain the N-containing organics from cellulose under mild conditions, hydrothermal liquefaction of cellulose in the presence of ammonia was conducted in this study. The results showed that the increasing reaction temperature and prolonging time facilitated the conversion of cellulose in hydrothermal liquefaction (HTL) with NH3·H2O and decreased the amount of solid residue. Reaction temperature showed more influence than reaction time on solid residue formation. The components of bio-oil were significantly affected by reaction temperature and reaction time. Electrospray ionization-Fourier transform-ion cyclotron resonance-mass spectrometry (ESI FT-ICR MS) provided an insight for understanding the distribution of the different kinds of N-heterocycle compounds in the bio-oil. The possible reaction pathway of N-heterocycle compounds formation from cellulose during hydrothermal liquefaction with NH3·H2O was proposed.

Thallium concentrations, sources and ecological risk in the surface sediments of the Yangtze Estuary and its adjacent east China marginal sea: A baseline study.

The distribution characteristics, sources and ecological risk of thallium (Tl) in the surface sediments of Yangtze Estuary and its adjacent sea were studied. Tl concentrations ranged from 0.369 to 1.197 µg g-1 with an average of 0.674 µg g-1, which was slightly higher than the corresponding background values. Tl concentrations were relatively high in sediments of the south bank of Chongming Island and the Hangzhou Bay mouth, and gradually decreased from inner shelf to outer seas. The variation trend of Tl concentrations was controlled by sediment characteristics, hydrodynamic conditions and sources together. The sediment flux of Tl in the study area was 428.6 t/yr. The Yangtze River, the Yellow River and atmospheric inputs of Tl accounted for 52.7%, 10.5%, and 0.15% of the total sediment flux, respectively. The result of potential ecological index indicated that Tl in surface sediments of the study area had no threat to the ecological environment.

Radial Extracorporeal Shock Wave Therapy in an Individual With Primary Trigeminal Neuralgia: A Case Report and Literature Review.

A patient with primary trigeminal neuralgia exhibited pain relief without medication after radial extracorporeal shock wave therapy. The 52-yr-old woman had a 3-yr history of primary trigeminal neuralgia, involving the right maxillary division (V2) and the mandibular division (V3). She became refractory to carbamazepine and exhibited hepatic dysfunction. She hence received 3000 to 6000 impulses of craniofacial radial extracorporeal shock wave therapy to the region centered on the surface projection of the trigeminal ganglion and pain areas at 10 Hz; the intensity ranged from 1.4 to 4.5 bars twice per week for 8 wks. At baseline, and 1, 2, and 5 mos after treatment, the Barrow Neurological Institute scores were IV, IIIa, II, and II, and the visual analog scale scores were 8, 3, 1, and 1, respectively. No complications or adverse effects were observed. The hepatic function returned to normal after the discontinuation of carbamazepine. This case report demonstrates the feasibility of radial extracorporeal shock wave therapy for primary trigeminal neuralgia without complications or adverse effects with careful regulation of the therapy intensity.

Electrospun PCL/gelatin composite nanofiber structures for effective guided bone regeneration membranes.

Guided bone regeneration (GBR) membranes have been proved of great benefit for bone tissue engineering due to the improvement of cell attachment and proliferation. To develop GBR membranes with better biocompatibility and more proper degradation ability, here we fabricated polycaprolactone (PCL, polymer)/gelatin (protein) hybrid nanofibrous GBR membranes via electrospinning, followed by crosslinking with genipin. Acetic acid (HAc) was utilized to resolve the phase separation of PCL and gelatin, therefore homogeneous PCL/gelatin hybrid nanofibers with different ratios were successfully prepared. FTIR, XPS, TGA, DSC results proved that the proportion of PCL and gelatin in the as-spun nanofiber membranes could be simply adjusted by changing the weight ratio of PCL and gelatin in the spinning solution. SEM and AFM images demonstrated that all the nanofibers possessed uniform and smooth structures both in two dimension (2D) and three dimension (3D). The mechanical tests showed that these nanofibers exhibited appropriate tensile and strength properties, which were suitable for bone tissue engineering. CCK-8 and SEM images revealed that all the membranes were biocompatible to MC3T3-e1 cells. In addition, the in vitro osteogenesis characterizations, alizarin red in normal medium and osteogenesis medium, indicated that the nanofibers could promote bone formation. Therefore, all these results could suggest that our design of electrospun polymer/protein nanofiber membranes was effective for guided bone regeneration.

Tribo-biological deposits on the articulating surfaces of metal-on-polyethylene total hip implants retrieved from patients.

Artificial total hip arthroplasty (THA) is one of the most effective orthopaedic surgeries that has been used for decades. However, wear of the articulating surfaces is one of the key failure causes limiting the lifetime of total hip implant. In this paper, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were employed to explore the composition and formation mechanism of the tribo-layer on the articulating surfaces of metal-on-polyethylene (MoPE) implants retrieved from patients. Results showed that, in contrast to conventional understanding, the attached tribo-layer contained not only denatured proteins but also a fraction of polymer particles. The formation of the tribo-layer was believed to relate to lubrication regime, which was supposed to be largely affected by the nature of the ultra-high-molecule-weight-polyethylene (UHMWPE). Wear and formation of tribo-layer could be minimized in elasto-hydrodynamic lubrication (EHL) regime when the UHMWPE was less stiff and have a morphology containing micro-pits; whereas the wear was more severe and tribo-layer formed in boundary lubrication. Our results and analyses suggest that enhancing interface lubrication may be more effective on reducing wear than increasing the hardness of material. This finding may shed light on the design strategy of artificial hip joints.

Bilaterally Primary Cementless Total Hip Arthroplasty for Severe Hip Ankylosis with Ankylosing Spondylitis.

OBJECTIVES: Total hip arthroplasty is a reliable therapeutic intervention in patients with ankylosing spondylitis, in whom the aims of surgery are to reduce pain, restore hip function and improve quality of life. The current study is a retrospective analysis of the clinical and radiographic findings in a consecutive series of patients with hip ankylosis associated with severe ankylosing spondylitis who underwent bilateral primary total hip arthroplasty using non-cemented components. METHODS: From June 2008 to May 2012, total hip arthroplasty was performed on 34 hips in 17 patients with bilateral ankylosis caused by ankylosing spondylitis. The study patients included 13 men and 4 women with a mean age of 24.2 years. The mean duration of disease was 8.3 years and the average duration of hip involvement was 7.6 years. All patients had severe hip pain and dysfunction with bilateral bony ankylosis and no range of motion preoperatively and all underwent bilateral cementless total hip arthroplasty performed by a single surgeon. Joint pain, range of motion (ROM), and Harris hip scores were assessed to evaluate the postoperative results. RESULTS: At a mean follow-up of 31.7 months, all patients had experienced significant clinical improvement in function, ROM, posture and ambulation. At the final follow-up, the mean postoperative flexion ROM was 134.4° compared with 0° preoperatively. Similar improvements were seen in hip abduction, adduction, internal rotation and external rotation. Postoperatively, 23 hips were completely pain-free, six had only occasional discomfort, three mild to moderate pain and two severe pain. The average Harris Hip Score improved from 23.7 preoperatively to 65.8 postoperatively. No stems had loosened at the final follow-up in any patient, nor had any revision surgery been required. CONCLUSIONS: Bilateral severe hip ankylosis in patients with ankylosing spondylitis can be treated with cementless bilateral synchronous total hip arthroplasty, which can greatly improve hip joint function and relieve pain without significant complications. Provided the overall physical condition of a patient and their economic situation make surgery a feasible option and the surgeon is experienced, this treatment is a worthwhile surgical intervention for bilateral hip bony ankylosis. However, the technically demanding nature of the procedure and potential pre- and post-operative problems should not be underestimated.

Reconstruction of beagle hemi-mandibular defects with allogenic mandibular scaffolds and autologous mesenchymal stem cells.

OBJECTIVE: Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs) can increase the integration of massive allografts (hemi-mandible) in a large animal model. METHODS: Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at 4 (n = 4), 12 (n = 4), 24 (n = 4) or 48 weeks (n = 3) postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD) of transplants were used to evaluate defect reconstruction outcomes. RESULTS: Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05), and all micro-architectural parameters were significantly different between groups (p<0.05). Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed. CONCLUSIONS: Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a combination of MSCs and osteoinductive growth factors.

Mesenchymal stem cells in tissue repairing and regeneration: Progress and future.

The presence of mesenchymal progenitor cells within bone marrow has been known since the late nineteenth century. To date, mesenchymal stem cells (MSCs) have been isolated from several different connective tissues, such as adipose tissue, muscle, placenta, umbilical cord matrix, blood, liver, and dental pulp. Bone marrow, however, is still one of the major sources of MSCs for preclinical and clinical research. MSCs were first evaluated for regenerative applications and have since been shown to directly influence the immune system and to promote neovascularization of ischemic tissues. These observations have prompted a new era of MSC transplantation as a treatment for various diseases. In this review, we summarize the important studies that have investigated the use of MSCs as a therapeutic agent for regenerative medicine, immune disorders, cancer, and gene therapy. Furthermore, we discuss the mechanisms involved in MSC-based therapies and clinical-grade MSC manufacturing.

Surface hydrophilic modification of polyethersulfone membranes by surface-initiated ATRP with enhanced blood compatibility.

Surface-initiated atom transfer radical polymerization (SI-ATRP) was used to tailor the functionality of polyethersulfone (PES) membranes. A two-step method including nitration reaction and amination reaction was used to synthesize aminated polyethersulfone (PES-NH2) for the preparation of PES/PES-NH2 membranes. Covalently tethered hydrophilic polymer brushes of poly(N-vinylpyrrolidone) (PVP) were prepared via SI-ATRP at low temperature in an aqueous solvent. Attenuated total reflection-Fourier transform infrared (ATR-FTIR), scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS), and water contact angle were used to characterize the modified membranes surfaces. The PVP-grafted PES membranes showed lower protein adsorption and suppressed platelet adhesion compared with the pristine PES membrane. Moreover, the activated partial thromboplastin time (APTT) for the PVP-grafted PES membranes was increased. These results indicated that the surface hydrophilic modification by grafting PVP brushes provided practical application for the PES membranes with good blood compatibility.

The role of systemically delivered bone marrow-derived mesenchymal stem cells in the regeneration of periodontal tissues.

PURPOSE: Recent studies have shown that periodontal ligament stem cells (PDLSCs) play a key role in periodontal regeneration. However, the origin of these cells remains unclear. Meanwhile, bone marrow is thought to be the most common source of adult stem cells in many tissues and organs. Thus, the present investigation sought to determine whether systemically delivered bone marrow-derived mesenchymal stem cells (BM-MSCs) could participate in periodontal regeneration and differentiate into periodontal-specific cells and to explore the origin of PDLSCs. METHODS: Enhanced green fluorescent protein (EGFP)-labeled BMMSCs were delivered into lethally irradiated rats by intra-bone marrow (IBM) transplantation. Four weeks after transplantation, periodontal defects with and without infection of anaerobic cultured Porphyromonas gingivalis were established. The animals were killed 1, 2, 4, or 6 weeks after periodontal defect surgery. Histomorphologic analysis, direct observation with the fluorescence microscope, and immunohistochemical staining were performed to evaluate the localization and differentiation of BM-MSCs. RESULTS: EGFP-positive BM-MSCs could be observed as early as 1 week after surgery, and the number of EGFP-positive cells reached a maximum at 2 weeks. Meanwhile, EGFP-positive cells were observed in the newly formed bone, PDL, and cementum 4 weeks after surgery. Immunohistochemical staining verified that EGFP-positive BM-MSCs could differentiate into osteoblasts. CONCLUSIONS: These findings provide direct evidence that BM-MSCs can participate in and modulate periodontal regeneration.

Why to synthesize vaterite polymorph of calcium carbonate on the cellulose matrix via sonochemistry process?

Vaterite is an important biomedical material due to its features such as high specific surface area, high solubility, high dispersion, and small specific gravity. The purposes of this article were to explore the growth mechanism of vaterite on the cellulose matrix via sonochmistry process. In the work reported herein, the influences of experimental parameters on the polymorph of calcium carbonate were investigated in detail. The calcium carbonate crystals on the cellulose matrix were characterized by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Experimental results revealed that all the reactants, solvent, and synthesis method played an important role in the polymorph of calcium carbonate. The pure phase of vaterite polymorph was obtained using Na2CO3 as reactant in ethylene glycol on the cellulose matrix via sonochmistry process. Based on the experimental results, one can conclude that the synthesis of vaterite polymorph is a system process.

Application of induced pluripotent stem cells in generation of a tissue-engineered tooth-like structure.

Stem cells, such as adult stem cells or embryonic stem cells, are the most important seed cells employed in tooth tissue engineering. Even though dental-derived stem cells are a good source of seed cells for such procedures, they are not often used in clinical applications because of the limited supply. Induced pluripotent stem (iPS) cells, with their high proliferation and differentiation ability, are now considered a promising alternative. The objectives of this study were to assess the role of iPS cells in tooth tissue engineering. We used real-time polymerase chain reaction to confirm that mouse iPS (miPS) cells can be induced to express both odontogenic and osteogenic gene profiles. We then established a tooth germ model and transplanted the recombinant tooth germ into a mouse subrenal capsule for 4 weeks to reproduce early-tooth organogenesis. After 4 weeks, hematoxylin and eosin staining results showed newly formed bone-like and dental pulp-like areas. Further immunohistochemical staining confirmed that osteopontin was present in the apical part of the tooth-like structure. These results demonstrate that miPS cells have the potential to differentiate into odontogenic cells, confirming that they could be a new source of seed cells for use in tooth tissue engineering.

Growth stimulating effect on queen bee larvae of histone deacetylase inhibitors.

Royal jelly (RJ) is a widely used natural food. It is also a major source of nutrition for queen bees and plays a key role in their development. RJ is secreted from the hypopharyngeal and mandibular glands of young adult worker bees. The regulation of gene expression in these two glands may influence the development of queen bees by affecting the content of RJ. This study investigated the epigenetic effects in these two glands in young adult worker bees treated with histone deacetylase inhibitors (HDACis), a U.S. Food and Drug Administration-approved drug, suberoylanilide hydroxamic acid (SAHA), and NBM-HD-1, a novel compound synthesized in this laboratory. Western blot analyses indicated that the levels of acetyl-histone 3 and p21 protein expression in MCF-7 cells increased markedly after treatment with NBM-HD-1. The data proved that NBM-HD-1 was a novel and potent HDACi. Furthermore, a method of affecting epigenetic regulation of the mrjp family gene in the hypopharyngeal and mandibular glands of young adult worker bees was developed by feeding young adult worker bees HDACi. Epigenetic regulation produced several important biological effects. A marked change in the protein composition of the RJ secreted from these treated bees was found. Only the ratio of specific major royal jelly protein 3 (MRJP3) was significantly altered in the treated bees versus the untreated controls. Other MRJP family proteins did not change. This alteration in the ratio of royal jelly proteins resulted in a significant increase in the body size of queen bee larvae. The data seem to suggest that HDACis may play an important role in the epigenetic regulation of the hypopharyngeal and mandibular glands of young adult worker bees. They appear to change mrjp3 gene expression and alter the ratio of MRJP3 protein in RJ. This study presents the first evidence that HDACis are capable of regulating the ratio of MRJP3 proteins in RJ, which has the potential to change the body size of queen bees during their development.