Construction of selenium-embedded mesoporous silica with improved antibacterial activity.

In this work, different concentrations of Se-incorporated mesoporous silica nanospheres (MSNs) (5Se/MSNs and 10Se/MSNs) were successfully synthesized via an in-situ one-pot method. Their physicochemical properties were characterized by X-ray diffraction (XRD), transmission electron microscopy, and X-ray photoelectron spectroscopy (XPS). The release behaviors of Se and Si were investigated in a phosphate-buffered saline (pH = 5.5, 7.4) solution (PBS). In vitro antibacterial properties of the prepared samples were evaluated with Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The cytocompatibilities of the samples were then assessed using L929 cells. Se nanoparticles were successfully loaded onto the outer and inner surfaces of hierarchical mesoporous silica. The sizes of the Se/MSNs nanoparticles were approximately 120 nm for 5Se/MSNs and 210 nm for 10Se/MSNs. The XRD and XPS results showed that Se mainly existed in the form of Se0 in the samples. The Se/MSNs exhibited stable and sustained release of both Si and Se in PBS solution. In vitro antibactericidal tests indicated that the Se/MSNs could exhibit better antibacterial activity against S. aureus than pure Se nanoparticles after 6 and 24 h of culturing. The minimal inhibitory concentration (MIC) of 10Se/MSN was 100 µg mL-1. However, the Se/MSNs exhibited no inhibitory effect on E. coli bacteria. Furthermore, all the samples exhibited excellent cell viability. These studies demonstrate initial in vitro antibacterial activity and good cytocompatibility of Se/MSNs and their potential application in antibacterial nanomedicine.

Cytocompatibility and Bone-Formation Potential of Se-Coated 316L Stainless Steel with Nano-Pit Arrays.

316L stainless steel is still widely applied in joint replacement and orthopedic surgery due to its mechanical properties, corrosion resistance and relatively low price. In this study, electrochemical oxidation and nanoscale coating were used to fabricate Se-coated 316L stainless steel with nano-pit arrays to enhance its surface characteristics, biocompatibility and osseointegration ability. The modified 316L stainless steel was tested via field emission scanning microscopy (FESEM), energy-dispersive X-ray spectrometry (EDS), X-ray photoelectron spectroscopy (XPS) and Se release studies. The results of this study showed that the nano-pit arrays were 50 nm in diameter and that the Se coating consisted primarily of elemental Se and exhibited sustained release. The biological response of the samples was evaluated using in vitro rat bone marrow mesenchymal stem cell (rBMSCs) experiments and in vivo animal experiments. The modified 316L stainless steel displays enhanced abilities of cell adhesion, proliferation and osteogenic activity, as shown by FESEM, CCK-8 assay, immunofluorescence microscopy (IF) and alkaline phosphatase (ALP) activity assay in vitro and additional new bone formation in vivo, indicating its outstanding cytocompatibility and osteogenic differentiation ability. More importantly, the Se coating can upregulate gene expression of OPN, RUNX-2 and ALP, indicating that the nano-Se-coated 316L stainless steel with nano-pit arrays is a promising biomedical material for implants in orthopedic or dental clinic applications.

Enhanced apatite-forming ability and antibacterial activity of porous anodic alumina embedded with CaO-SiO2-Ag2O bioactive materials.

In this study, to provide porous anodic alumina (PAA) with bioactivity and anti-bacterial properties, sol-gel derived bioactive CaO-SiO2-Ag2O materials were loaded onto and into PAA nano-pores (termed CaO-SiO2-Ag2O/PAA) by a sol-dipping method and subsequent calcination of the gel-glasses. The in vitro apatite-forming ability of the CaO-SiO2-Ag2O/PAA specimens was evaluated by soaking them in simulated body fluid (SBF). The surface microstructure and chemical property before and after soaking in SBF were characterized. Release of ions into the SBF was also measured. In addition, the antibacterial properties of the samples were tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results showed that CaO-SiO2-Ag2O bioactive materials were successfully decorated onto and into PAA nano-pores. In vitro SBF experiments revealed that the CaO-SiO2-Ag2O/PAA specimens dramatically enhanced the apatite-forming ability of PAA in SBF and Ca, Si and Ag ions were released from the samples in a sustained and slow manner. Importantly, E. coli and S. aureus were both killed on the CaO-SiO2-Ag2O/PAA (by 100%) samples compared to PAA controls after 3 days of culture. In summary, this study demonstrated that the CaO-SiO2-Ag2O/PAA samples possess good apatite-forming ability and high antibacterial activity causing it to be a promising bioactive coating candidate for implant materials for orthopedic applications.

Bone marrow mesenchymal stem cells protect against bleomycin-induced pulmonary fibrosis in rat by activating Nrf2 signaling.

Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant may play an important role in many of the processes of inflammation and fibrosis. Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress. Mesenchymal stem cells (MSC) are in clinical trials for widespread indications including musculoskeletal, neurological, cardiac and haematological disorders. One emerging concept is that MSCs may have paracrine, rather than a functional, roles in lung injury repair and regeneration. In the present study, we investigated bone marrow mesenchymal stem cells (BMSCs) for the treatment of bleomycin-induced pulmonary fibrosis. Our results showed that BMSCs administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. The gene expression levels of NAD(P)H: quinine oxidoreductase 1 (NQO1), gama-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), attenuated by bleomycin, were increased up to basal levels after BMSCs transplantation. BMSCs significantly increased superoxide dismutase (SOD) activity and inhibited malondialdehyde (MDA) production in the injured lung. The present study provides evidence that BMSCs may be a potential therapeutic reagent for the treatment of lung fibrosis.

Understanding improved osteoblast behavior on select nanoporous anodic alumina.

The aim of this study was to prepare different sized porous anodic alumina (PAA) and examine preosteoblast (MC3T3-E1) attachment and proliferation on such nanoporous surfaces. In this study, PAA with tunable pore sizes (25 nm, 50 nm, and 75 nm) were fabricated by a two-step anodizing procedure in oxalic acid. The surface morphology and elemental composition of PAA were characterized by field emission scanning electron microscopy and X-ray photoelectron spectroscopy analysis. The nanopore arrays on all of the PAA samples were highly regular. X-ray photoelectron spectroscopy analysis suggested that the chemistry of PAA and flat aluminum surfaces were similar. However, contact angles were significantly greater on all of the PAA compared to flat aluminum substrates, which consequently altered protein adsorption profiles. The attachment and proliferation of preosteoblasts were determined for up to 7 days in culture using field emission scanning electron microscopy and a Cell Counting Kit-8. Results showed that nanoporous surfaces did not enhance initial preosteoblast attachment, whereas preosteoblast proliferation dramatically increased when the PAA pore size was either 50 nm or 75 nm compared to all other samples (P<0.05). Thus, this study showed that one can alter surface energy of aluminum by modifying surface nano-roughness alone (and not changing chemistry) through an anodization process to improve osteoblast density, and, thus, should be further studied as a bioactive interface for orthopedic applications.

[The role of JNK in apoptosis of renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose].

OBJECTIVE: To explore the signal transduction mechanisms of apoptosis in renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose. METHODS: Healthy SD rats were randomly divided into 3 groups: normal control group (A), stable high blood glucose group (B) and fluctuant high blood glucose group (C). Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg), and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time point every day. The superoxide dismutase (SOD) activity and the content of malonaldehyde (MDA) in renal tissue homogenate were detected with colorimetry. The protein expression of Nox4 and JNK were examined by immunohistochemistry and Western blot. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). RESULTS: After 12 experimental weeks, significantly increased cell apoptosis, up-regulation of Nox4 and P-JNK expression in renal tubular epithelial cells were observed in B and C groups compared with those in A group. The MDA content increased and SOD activity decreased in renal tissue in B and C groups. Above effects were more obviously shown in C group. CONCLUSION: Fluctuant high blood glucose induced more apoptosis of renal tubular epithelial cell than stable high blood glucose in diabetic kidney, which might be related to the activation of JNK signal transduction pathway.

[Effects of cyclosporine A on pneumocyte apoptosis with lung ischemia/reperfusion injury in rats].

OBJECTIVE: To investigate the effects of cyclosporine A (CsA), a powerful inhibitor of mitochondrial permeability transition pore (MPTP), on pneumocyte apoptosis, the release of cytochrome C and the activity of caspase-3 after lung ischemia/reperfusion, and explore the mechanisms. METHODS: Single lung in situ ischemia/reperfusion animal model was used. 30 SD rats were randomly divided into three groups (n = 10): sham (S) group, ischemia/reperfusion (I/R) group and cyclosporine A (CsA) group. Apoptosis of pneumocyte was assessed by TUNEL method, cytochrome C (CytC) in cytoplasm was detected by immunohistochemistry techniques, and the activity of caspase-3 was measured with spectrophotometer. RESULTS: The content of CytC in cytoplasm, the activity of caspase-3, and the value of apoptosis index (AI) in ischemia/reperfusion group were evidently higher than that in S group (P < 0.01). CsA suppressed apoptosis as well as CytC release and caspase-3 activity (P < 0.01). CONCLUSION: CsA can prevent the release of cytochrome C, block the apoptosis of pneumocyte accordingly maybe by closing the MPTP.

[Effect of ligustrazine and L-arginine on function of mitochondria in myocardium after ischemia/reperfusion injury of myocardium in rabbits].

AIM: To study the effect of ligustrazine (LGT) and L-arginine(L-Arg)on function of mitochondria in myocardium after myocardial ischemia/reperfusion injury (MI/RI). METHODS: 50 rabbits were randomly divided into five groups (n=10): Control group(A), MI/R group(B), MI/R + LGT group (C), MI/R+ L-Arg group (D), MI/R+ LGT + L-Arg group (E). The mitochondrial respiratory function, Ca2+ concentration ([Ca2+]m), malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were deter mined. Meanwhile, the contents of ATP and EC in the myocardial tissue were measured, respectively. RESULTS: It was found that mitochondrial respiratory control rate (RCR), state 3 (ST3), SOD in C, D, E group were higher than those of B group, state 4 (ST4), [Ca2+]m, MDA were lower than those of B group, ATP and EC levels of myocardial tissue were higher than those in B group; and there were not significant differences between E and A group of above. CONCLUSION: LGT and IL-Arg can improve function of mitochondria in myocardium after ischemia/reperfusion injury of myocardium in rabbits by decreasing oxygen free radical level and Ca" overload in the mitochondria.

[Effect of ligustrazine on the expression and activity of heme oxygenase-1 in the pulmonary ischemia/reperfusion injury in rabbits].

AIM: To explore the effect of ligustrazine injection on the expression of heme oxygenase-1 (HO-1) in rabbits with pulmonary ischemia/reperfusion injury after. METHODS: Single lung ischemia/reperfusion injury animal model was used in vivo. Twenty rabbits were randomly divided into two groups( n = 10, in each), pulmonary ischemia/reperfusion injury (I/R) group and I/R + ligustrazine injection (LGT) group. The tissue slides were stained by immunohistochemistry (IHC) and in situ hybridization (ISH) for HO-1 to detect the expression of HO-1 in lung and to analyze the absorbance, wet to dry ratio of lung tissue weight (W/D) and the injured alveoli rate (IAR) were measured at 180 minutes after lung reperfusion. Meanwhile the lung tissue slide was prepared for electron microscopic observation at 180 minutes after reperfusion. RESULTS: HO-1 expression was upregulated in two groups in the pulmonary endothelial cells, part of pulmonary vascular smooth muscle cells, extima of vessels and epithelial cells of airway, the absorbance was 0.168 +/- 0.016 (0.148 +/- 0.013), 0.186 +/- 0.014 (0.158 +/- 0.012) respectively.The LGTI group showed higher absorbance than those of the I/R group (P < 0.01), lower W/D and IAR values than those of the I/R group (P < 0.01) significantly and lighter abnormal changes of the lung tissue in morphology than those of the I/R group. CONCLUSION: Ligustrazine injection possesses notable protective effects on I/R in rabbits by increasing the expression of HO-1 in lung.