Photocatalyst-free visible-light-induced highly selective acylation of purine nucleosides at the C6 position.

A protocol for visible-light-induced C-H acylation selectively at the C6 position of purine nucleosides with aldehydes under photocatalyst-free conditions was established herein. This protocol allows the green, mild, and efficient functionalization of various purine nucleosides with a broad range of alkyl and aryl aldehydes.

Enamel-like tissue regeneration by using biomimetic enamel matrix proteins.

Enamel regeneration currently -is limited by our inability to duplicate artificially its complicated and well-aligned hydroxyapatite structure. The initial formation of enamel occurs in enamel organs where the ameloblasts secret enamel extracellular matrix formed a unique gel-like microenvironment. The enamel extracellular matrix is mainly composed by amelogenin and non-amelogenin. In this study, an innovative strategy was proposed to regenerate enamel-like tissue by constructing a microenvironment using biomimetic enamel matrix proteins (biomimetic EMPs) composed of modified leucine-rich amelogenin peptide (mLRAP) and non-amelogenin analog (NAA). Impressively, the regenerated enamel in this biomimetic EMPs on etched enamel surface produced prismatic structures, and showed similar mechanical properties to natural enamel. The results of X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed that regenerated crystal was hydroxyapatite. Molecular dynamics simulation analysis showed the binding energy between mLRAP and NAA were electrostatic forces and Van der Walls. These results introduced a promising strategy to induce crystal growth of enamel-like hydroxyapatite for biomimetic reproduction of materials with complicated hierarchical microstructures.

Acidic Monetite Complex Paste with Bleaching Property for In-depth Occlusion of Dentinal Tubules.

BACKGROUND: Dentin hypersensitivity (DH) is a common dental clinical condition presented with a short and sharp pain in response to physical and chemical stimuli. Currently no treatment regimen demonstrates long-lasting efficacy in treating DH, and unesthetic yellow tooth color is a concern to many patients with DH. AIM: To develop a bi-functional material which can occlude dentinal tubules in-depth and remineralize dentin for long-lasting protection of the dentin-pulp complex from stimuli and bleach the tooth at the same time. METHODS: A mixture containing CaO, H3PO4, polyethylene glycol and H2O2 at a specific ratio was mechanically ground using a planetary ball. The mineralizing complex paste was characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Dentin was exposed to the synthesized paste for 8 h and 24 h in vitro. The mineralizing property was evaluated using SEM and microhardness tests. Red tea-stained tooth slices were exposed to the synthesized paste for 8 h and 24 h in vitro. The bleaching effect was characterized by a spectrophotometer. RESULTS: The complex paste had very a fine texture, was injectable, and had a gel-like property with 2.6 (mass/volume) % H2O2 concentration. The X-ray diffraction pattern showed that the inorganic phase was mainly monetite (CaHPO4). The mineralizing complex paste induced the growth of inorganic crystals on the dentin surface and in-depth occlusion of dentin tubules by up to 80 µm. The regenerated crystals were integrated into the dentin tissue on the dentin surface and the wall of dentinal tubules with a microhardness of up to 126 MPa (versus 137 Mpa for dentin). The paste also bleached the stained dental slices. CONCLUSION: The mineralizing complex paste is a promising innovative material for efficient DH management by remineralizing dentin and in-depth occlusion of dentin tubules, as well as tooth bleaching.

Rapid regeneration of enamel-like-oriented inorganic crystals by using rotary evaporation.

Enamel, the hardest tissue in the human body, has excellent mechanical properties, mainly due to its highly ordered spatial structure. Fabricating enamel-like structure is still a challenge today. In this work, a simple and highly efficient method was introduced, using the silk fibroin as a template to regulate calcium- and phosphate- supersaturated solution to regenerate enamel-like hydroxyapatite crystals on various substrates (enamel, dentin, titanium, and polyethylene) under rotary evaporation. The enamel-like zinc oxide nanorod array structure was also successfully synthesized using the aforementioned method. This strategy provides a new approach to design and fabricate mineral crystals with particular orientation coatings for materials.

A tooth-binding antimicrobial peptide to prevent the formation of dental biofilm.

Dental caries is primarily caused by pathogenic bacteria infection, and Streptococcus mutans is considered a major cariogenic pathogen. Moreover, antimicrobial peptides have been considered an alternative to traditional antibiotics in treating caries. This study aimed to design a tooth-binding antimicrobial peptide and evaluate its antimicrobial efficacy against S. mutans. An antimicrobial peptide of polyphemusin I (PI) was modified by grafting a tooth-binding domain of diphosphoserine (Ser(p)-Ser(p)-) to create the peptide of Ser(p)-Ser(p)-polyphemusin I (DPS-PI). PI and DPS-PI were synthesized by Fmoc solid-phase peptide synthesis. The minimum inhibitory concentration of PI and DPS-PI against S. mutans were tested. Scanning electron microscopy (SEM) were used to observe the growth of S. mutans on PI and DPS-PI treated enamel surfaces. The growth of S. mutans was evaluated by optical density (OD) at 590 nm. Inhibition of dental plaque biofilm development in vivo were investigated. The cytocompatibility to bone mesenchymal stem cells (BMSCs) was tested. The MIC of PI and DPS-PI were 40 and 80 µg/ml, respectively. SEM images showed that S. mutans were sparsely distributed on the DPS-PI treated enamel surface. OD findings indicated that DPS-PI maintained its inhibition effect on S. mutans growth after 24 h. The incisor surfaces of rabbits treated with DPS-PI developed significantly less dental plaque biofilm than that on PI treated surfaces. The DPS-PI had good biocompatibility with the cells. We successfully constructed a novel tooth-binding antimicrobial peptide against S. mutans in vitro and inhibited dental plaque biofilm development in vivo. DPS-PI may provide a feasible alternative to conventional antibiotics for the prevention and treatment of dental caries. Dental caries is primarily caused by pathogenic bacteria infection, and Streptococcus mutans is considered a major cariogenic pathogen. A tooth-binding antimicrobial peptide was designed by grafted diphosphoserine (-Ser(p)-Ser(p)-) to the structure of polyphemusin I. This novel tooth-binding antimicrobial peptide can inhibit dental plaque biofilm development and thus provide a feasible alternative to conventional antibiotics for the prevention and treatment of dental caries.

MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide.

Although arsenic trioxide (ATO) is a well-known antileukemic drug used for acute promyelocytic leukemia treatment, the development of ATO resistance is still a big challenge. We previously reported that microRNA-204 (miR-204) was involved in the regulation of acute myeloid leukemia (AML) cell apoptosis, but its role in chemoresistance is poorly understood. In the present study, we showed that miR-204 was significantly increased in AML cells after ATO treatment. Interestingly, the increased miR-204 level that was negatively correlated with ATO induced the decrease in cell viability and baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression. Overexpression of miR-204 potentiated ATO-induced AML cell growth inhibition and apoptosis. Furthermore, miR-204 directly targets to the 3'-UTR of BIRC6. Upregulation of miR-204 decreased BIRC6 luciferase activity and expression, which subsequently enhanced the expression of p53. Restoration of BIRC6 markedly reversed the effect of miR-204 on the regulation of AML cell sensitivity to ATO. Taken together, our study demonstrates that miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis. miR-204 represents a novel target of ATO, and upregulation of miR-204 may be a useful strategy to improve the efficacy of ATO in AML treatment.

Mechanism and Effects of Polyphenol Derivatives for Modifying Collagen.

This study is aimed to investigate the relationship of the mechanism and the effect of polyphenol derivatives cross-linking collagen with polyphenol molecular structural complexity and reaction conditions of polyphenols with collagen and to present a reference for cross-linker selection. Three kinds of polyphenols were selected to cross-link collagen under nonoxidized and oxidized conditions in vitro. These polyphenols included tannic acid, which represents the most complex stereo structure and the highest number of phenolic hydroxyl groups; epigallocatechin gallate, which represents a moderately complex structure and contains fewer phenolic hydroxyl groups than tannic acid; and N-2-(3,4-dihydroxylphenyl) ethyl acrylamide, which represents only one hydroxyl phenol group. Particle size analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, attenuated total reflection Fourier transform infrared spectroscopy, and cross-linking degree analysis were conducted. Mechanical properties, thermal stability, swelling properties, hydrophilicity, and antienzymolysis properties were also determined. Results showed that all polyphenol derivatives cross-linked collagen mainly by noncovalent bonding under acidic nonoxidized conditions and by covalent bonding under alkaline-oxidized conditions. In general, the modification effect of polyphenol on collagen was related to its molecular complexity and the number of its phenolic hydroxyls. Several phenolic hydroxyls in the polyphenol derivative caused a good modification effect on collagen, especially under acidic nonoxidized conditions. Under alkaline conditions, each polyphenol was oxidized, resulting in improved cross-linking strength by covalent bonding compared to that under acidic nonoxidized condition via noncovalent bonding. The selection of cross-linkers and cross-linking conditions should be based on the purpose of collagen modification consistent with the effect of cross-linking.

MiR-204 acts as a potential therapeutic target in acute myeloid leukemia by increasing BIRC6-mediated apoptosis.

Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significantly downregulated in AML tissues and cell lines. In addition, overexpression of miR-204 induced growth inhibition and apoptosis in AML cells, including AML5, HL-60, Kasumi-1 and U937 cells. Cell cycle analysis further confirmed an augmentation in theapoptotic subG1 population by miR-204 overexpression. Mechanistically, baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) was identified as a direct target of miR-204. Enforcing miR-204 expression increased the luciferase activity and expression of BIRC6, as well as p53 and Bax expression. Moreover, restoration of BIRC6 reversed the pro-apoptotic effects of miR-204 overexpression in AML cells. Taken together, this study demonstrates that miR-204 causes AML cell apoptosis by targeting BIRC6, suggesting miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease. [BMB Reports 2018; 51(9): 444-449].

Analysis of computed tomography and pathological observations of non-Hodgkin lymphomas with peritoneal, omental and mesenteric involvement.

The aim of the present study was to evaluate the association between computed tomography (CT) images and the pathological observations of non-Hodgkin lymphoma (NHL) patients with peritoneal, omental and mesenteric involvement. In total, 26 patients suffering from an NHL with peritoneal, omental or mesenteric involvement were reviewed retrospectively, and the observed CT scan characteristics were analyzed. In addition, associations among the CT scan characteristics and the NHL subtypes, including diffuse large B-cell, mantle cell, follicular cell and T-cell lymphoma, were evaluated. The CT scan characteristics of the NHLs with peritoneal, omental and mesenteric involvement included peritoneal cord-like thickening, peritoneal omental nodular and swelling thickening, omental cake-like thickening and mesenteric mass. The probability of peritoneal linear, omental nodular and swelling thickening was found to be higher in diffuse large B-cell lymphoma cases compared with cases of other NHL subtypes (P<0.05). However, the probability of omental cake-like thickening and mesenteric mass was not found to be significantly different among the NHL subtypes (P>0.05). Signs of peritoneal, omental and mesenteric involvement were observed in the CT scans of all the NHL subtypes, particularly in diffuse large B-cell lymphoma cases. Therefore, linear, omental nodular and swelling thickening were characteristic of diffuse large B-cell lymphoma, while omental cake-like thickening and mesenteric mass were observed in all NHL subtypes.

Hiwi knockdown inhibits the growth of lung cancer in nude mice.

Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of SSCloAldebr cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell SSCloAldebr cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers.

Effect of RNA interference-related HiWi gene expression on the proliferation and apoptosis of lung cancer stem cells.

The aim of this study was to investigate the effect of HiWi gene silencing on lung cancer tumor stem cell proliferation and apoptosis using gene transfection and RNA interference. Moreover, we examined the feasibility of using the HiWi gene as a molecular target for the inhibition of lung cancer tumor stem cells (TSCs). shRNA eukaryotic expression vectors, pGenesil-2-HiWi1, pGenesil-2-HiWi2263 and pGenesil-2-control, targeting the HiWi gene were constructed. PBS served as the control group. The expression vector of the target HiWi gene shRNA was transfected into lung cancer TSCs with PEI as the medium. The conditions of lung cancer TSC proliferation and apoptosis in each group were examined using an MTT assay, fluorescence-activated cell sorting and Annexin V staining. The results showed that 24 h after transfection, the proliferation inhibition rates in the pGenesil-2-HiWi2263 (81.62%) and pGenesil-2-HiWi1 (73.16%) groups were higher as compared to the proliferation inhibition rate in the pGenesil-2-control group (8.54%). The apoptotic ratios in the pGenesil-2-HiWi1 and pGenesil-2-HiWi2263 groups were 26.16±1.21 and 28.06±1.78%, respectively, were higher as compared to those in the pGenesil-2-control group 2.86±0.09% (P<0.01). Our results suggest that HiWi gene silencing decreases proliferation and promotes apoptosis of lung cancer TSCs. Therefore, the HiWi gene could be used as a molecular target for the inhibition of the growth of lung cancer TSCs, which has potential value for the treatment of lung cancer.