Visible-Light-Induced Diselenide-Crosslinked Polymeric Micelles for ROS-Triggered Drug Delivery.

To synthesize an effective and versatile nano-platform serving as a promising carrier for controlled drug delivery, visible-light-induced diselenide-crosslinked polyurethane micelles were designed and prepared for ROS-triggered on-demand doxorubicin (DOX) release. A rationally designed amphiphilic block copolymer, poly(ethylene glycol)-b-poly(diselenolane diol-co-isophorone diisocyanate)-b-poly(ethylene glycol) (PEG-b-PUSe-b-PEG), which incorporates dangling diselenolane groups within the hydrophobic PU segments, was initially synthesized through the polycondensation reaction. In aqueous media, this type of amphiphilic block copolymer can self-assemble into micellar aggregates and encapsulate DOX within the micellar core, forming DOX-loaded micelles that are subsequently in situ core-crosslinked by diselenides via a visible-light-triggered metathesis reaction of Se-Se bonds. Compared with the non-crosslinked micelles (NCLMs), the as-prepared diselenide-crosslinked micelles (CLMs) exhibited a smaller particle size and improved colloidal stability. In vitro release studies have demonstrated suppressed drug release behavior for CLMs in physiological conditions, as compared to the NCLMs, whereas a burst release of DOX occurred upon exposure to an oxidation environment. Moreover, MTT assay results have revealed that the crosslinked polyurethane micelles displayed no significant cytotoxicity towards HeLa cells. Cellular uptake analyses have suggested the effective internalization of DOX-loaded crosslinked micelles and DOX release within cancer cells. These findings suggest that this kind of ROS-triggered reversibly crosslinked polyurethane micelles hold significant potential as a ROS-responsive drug delivery system.

Manipulation of Multiple Cell-Cell Interactions by Tunable DNA Scaffold Networks.

Manipulation of cell-cell interactions via cell surface engineering has potential biomedical applications in tissue engineering and cell therapy. However, manipulation of the comprehensive and multiple intercellular interactions remains a challenge and missing elements. Herein, utilizing a DNA triangular prism (TP) and a branched polymer (BP) as functional modules, we fabricate tunable DNA scaffold networks on the cell surface. The responsiveness of cell-cell recognition, aggregation and dissociation could be modulated by aptamer-functionalized DNA scaffold networks with high accuracy and specificity. By regulating the DNA scaffold networks coated on the cell surface, controlled intercellular molecular transportation is achieved. Our tunable network provides a simple and extendible strategy which addresses a current need in cell surface engineering to precisely manipulate cell-cell interactions and shows promise as a general tool for controllable cell behavior.

A Cascade Signaling Network between Artificial Cells Switching Activity of Synthetic Transmembrane Channels.

Cell-cell communication plays a vital role in biological activities; in particular, membrane-protein interactions are profoundly significant. In order to explore the underlying mechanism of intercellular signaling pathways, a full range of artificial systems have been explored. However, many of them are complicated and uncontrollable. Herein we designed an artificial signal transduction system able to control the influx of environmental ions by triggering the activation of synthetic transmembrane channels immobilized on giant membrane vesicles (GMVs). A membrane protein-like stimulator from one GMV community (GMVB) stimulates a receptor on another GMV community (GMVA) to release ssDNA messengers, resulting in the activation of synthetic transmembrane channels to enable the influx of ions. This event, in turn, triggers signal responses encapsulated in the GMVA protocell model. By mimicking natural signal transduction pathways, this novel prototype provides a workable tool for investigating cell-cell communication and expands biological signaling systems in general as well as explores useful platforms for addressing scientific problems which involve materials science, chemistry, and medicine.

Osteopontin Promotes Bone Destruction in Periapical Periodontitis by Activating the NF-κB Pathway.

BACKGROUND/AIMS: Periapical periodontitis is caused by bacterial infection and results in both one destruction and tooth loss. Osteopontin (OPN) is a secreted phosphorylated glycoprotein that participates in bone metabolism. METHODS: Thirty-three patients with chronic periapical periodontitis and 10 patients who had undergone the orthodontic removal of healthy tooth tissue (control) at the periodontal ligament were investigated, and an animal model of mouse periapical periodontitis was established for an in vivo analysis. The relationship between OPN and bone destruction during periapical periodontitis was analyzed. Osteoblasts and osteoclasts were cultured in vitro and treated with lipopolysaccharide. An inhibitor of NF-κB was used to pretreat the transfected cells. RESULTS: OPN increased osteoclast proliferation and differentiation, but reduced osteoblasts proliferation and differentiation. OPN activated the NF-κB pathway during periapical periodontitis and accelerated the transfer and phosphorylation of P65 from the cytoplasm to the nucleus. CONCLUSION: This study demonstrated that OPN played important roles in the progression of periapical periodontitis, and a dual role in bone metabolism during periapical periodontitis, linking osteoclasts and osteoblasts. The underlying mechanism may be related to the NF-κB pathway.

Efficacy of ultrasound-guided radiofrequency ablation of papillary thyroid microcarcinoma after one year.

OBJECTIVE: This study aims to evaluate the feasibility and safety of percutaneous radiofrequency ablation guided by ultrasound for treating papillary thyroid microcarcinoma. METHOD: At our institution, fifty people who had been treated for micropapillary thyroid cancer with ultrasound-guided radiofrequency ablation were chosen. Thyroid function was evaluated after one month, and the volume of the ablation region was assessed immediately, 3, 6, and 12 months after treatment. At the same time, the complications or adverse reactions after treatment were evaluated. RESULTS: As time passed, the volume of the ablation area decreased gradually, showing a regression trend. There was a significant difference in the volume of the ablation area between adjacent groups (P < 0.05), and the tumor volume reduction ratio (VRR) of the ablation area was a statistically significant difference between adjacent groups (P < 0.05). There was no significant difference between the indexes related to thyroid function before and after treatment(P > 0.05). No local recurrence or distant metastasis was found during follow-up; The most common complication after the operation was a slight pain in the neck. A few patients had toothache and neck swelling symptoms, and the above symptoms subsided within 24 h after the operation. CONCLUSION: Ultrasound-guided radiofrequency ablation is safe and effective for treating single-focus micropapillary thyroid carcinoma while retaining thyroid function, with few and minor complications, which can be used as an ideal surgical option.

Flexible and temperature-responsive hydrogel dressing for real-time and remote wound healing monitoring.

Wound management is highly clinically desirable due to the complexity and diversity of the wound repair process. However, it is still a major clinical challenge to develop a wound dressing with the capabilities of real-time and remote monitoring during wound healing. Herein, we have designed a polymer-based wound dressing in the form of a conductive, soft, temperature-responsive, antibacterial and biocompatible hydrogel, which is composed of polyacrylic acid (PAA)-grafted poly(N-isopropylacrylamide) (PNIPAM), vinyl-based polyacrylamide (PAM) and silver nanowires (AgNWs). In this hydrogel dressing, PAA-grafted PNIPAM acts as conformal interface and intrinsic temperature-responsive matrix, PAM helps to construct semi-penetrating polymer networks (SIPNs) to improve the mechanical properties, while the AgNWs introduce a three-dimensional conductive hydrogel network with antibacterial properties and sensing properties. The constructed hydrogel matrix was connected to a Bluetooth module to transmit the temperature changes wirelessly to a smart device. The design integrating a conductive hydrogel dressing with a wireless transmission module realized the real-time and wireless monitoring of the wound temperature, which is helpful to provide an early diagnosis of infection. This proof-of-concept study is highly promising in the development of new strategies to significantly improve wound management and other pathological diagnostics or treatments.

Logic-Gated Cell-Derived Nanovesicles via DNA-Based Smart Recognition Module.

Engineering cell-derived nanovesicles with active-targeting ligands is an important strategy to enhance the targeting efficiency. However, the enhanced binding capability to targeting cells also leads to the binding with nontarget cells that share the same biomarkers. DNA-based logic gate is a kind of molecular system that responds to chemical inputs by generating output signals, and the relationship between the input and the output is based on a certain logic. Thus, the DNA-based logic gate could provide a new approach to improve the delivery efficiency of the nanovesicle. In this work, we developed a DNA logic-gated module that coupled two tumor cell-targeting factors (e.g., low pH and a tumor cell biomarker) in a Boolean manner. Immobilization of this module on the surface of the nanovesicle enables the nanovesicle to sense tumor cell-targeting factors and regard these cues as inputs AND logic gate. With the guide of DNA-based logic gate, gold carbon dots (GCDs) encapsulated within nanovesicles were delivered into target cells, and then the intracellular redox status variation was reflected by fluorescence change of GCDs. Overall, we developed DNA logic-gated nanovesicles that contract different targeting factors into a unique tag for target cells. This facile functionalization strategy can pave the way for constructing smart nanovesicles and would broaden their application in the field of precision medicine and personalized treatment.

Biofabrication of nerve fibers with mimetic myelin sheath-like structure and aligned fibrous niche.

Nerve tissues contain hierarchically ordered nerve fibers, while each of the nerve fibers has nano-oriented fibrous extracellular matrix and a core-shell structure of tubular myelin sheath with elongated axons encapsulated. Here, we report, for the first time, a ready approach to fabricate biomimetic nerve fibers which are oriented and have a core-shell structure to spatially encapsulate two types of cells, neurons and Schwann cells. A microfluidic system was designed and assembled, which contained a coaxial triple-channel chip and a stretching loading device. Alginate was used first to assist the fabrication, which was washed away afterwards. The orientation of the biomimetic nerve fibers was optimized by the control of the compositions of methacrylate hyaluronan and fibrin, together with the parameters of microfluidic shearing and external stretching. Also, neurons and Schwann cells, which were respectively located in the core and shell of the fibers, displayed advanced biologic functions, including neurogenesis and myelinating maturation. We demonstrate that the neural performance is relatively good, compared to that resulted from individually encapsulated in single-layer microfibers. The present study brings insights to fabricate biomimetic nerve fibers for their potential in neuroscience research and nerve regeneration. Moreover, the present methodology on the fabrication of oriented fibers with different types of cells separately encapsulated should be applicable to biomimetic constructions of various tissues.

Effects of perinatal fluoride exposure on the expressions of miR-124 and miR-132 in hippocampus of mouse pups.

To investigate the effects of perinatal fluoride exposure on learning and memory ability of mouse offspring, ICR female mice were received different doses of sodium fluoride (0, 25, 50, 100 mg/L NaF) from pregnant day 7 to lactational day 21. Pups were exposed to fluoride through the cord blood and breast milk. Open field test showed that compared to the control group, perinatal fluoride exposure significantly decreased the number of entries into the center zone in 100 mg/L NaF group. In the eight-arm maze test, the number of working memory errors, reference memory errors, and the total arm entries were significantly increased in fluoride treatment groups, compared to the control group. Additionally, 100 mg/L NaF significantly elevated the expression levels of miR-124, miR-132, and DiGeorge syndrome chromosomal region 8 (DGCR8) in hippocampus of mouse pups at postnatal day (PND) 21. Contrarily, methyl CpG binding protein 2 (MeCP2) were dramatically reduced in 50 and 100 mg/L NaF groups, while cAMP-response element binding protein (CREB) mRNA level was significantly decreased in all fluoride groups. These findings suggested that the impairment of learning and memory in mouse offspring induced by perinatal fluoride exposure may partly result from the enhanced miR-124 and miR-132 and the alterations of their target genes.

Effects of Fluoride on SOD and CAT in Testis and Epididymis of Mice.

Oxidative damage has been implicated to be one of main mechanisms by which fluoride (F) induces toxic effects. Previous studies reported that F destroyed the epididymal structure of mouse and rabbit. Epididymis is the important place for sperm maturation. However, little is known about the effect of F on the oxidative stress status of epididymis. Therefore, the aim of the present study was to explore the changes in the activities and transcriptional levels of CuZn superoxide dismutase (CuZn-SOD, SOD1) and catalase (CAT), as well as the ultrastructure, in testis and epididymis of mice administrated with F. Sixty health Kunming mice were randomly divided into four groups. With one group untreated as controls, the others were treated with 25, 50, and 100 mg NaF/L in drinking water. After 10 weeks administration, mitochondrial ultrastructural changes in testis and epididymis were observed, including the incomplete membrane and the dissolved or disappeared cristae. Compared to the control group, the activities of both SOD1 and CAT in testis and epididymis were significantly reduced by 50 or 100 mg NaF exposure. In addition, the mRNA expressions of testicular SOD1 and CAT were also decreased significantly in 100 mg NaF/L group, while the SOD1 and CAT mRNA expressions in epididymides were significantly reduced in all F treatment groups. The above results suggest that in the presence of F, similar to testis, epididymis also loses the balance between oxidative stress and antioxidative defense, and perhaps more sensitive to F.

Degradation regulated bioactive hydrogel as the bioink with desirable moldability for microfluidic biofabrication.

Bioink development is vital in biofabriacation for generating three-dimensional (3D) tissue-like constructs. As potential candidates of bioinks, hydrogels need to meet the requirements of good moldability, initially strong mechanical properties and prominent bioactivity to guarantee cell vitality and further assembly. Enzyme-induced dynamic degradation is an efficient and biocompatible approach to improve the bioactivity of hydrogels through releasing space continuously for cell proliferation and promoting the functional establishing of engineered tissue. Here a novel bioink was designed by introducing alginate lyase into composite Alginate-GelMA hydrogels. Results showed that bioink with proper lyase content exhibited desirable modability and cytocompatibility. Then cell-laden osteon-like microfibers were engineered with the microfluidic device and diverse complex 3D constructs were also successfully assembled. This degradation-regulated bioink showed great promise in a variety of applications in tissue engineering and biomedical investigation.