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Objectives Gli1+ cells have received extensive attention in tissue homeostasis and injury mobilization. The aim of this study was to investigate whether Gli1+ cells respond to force and contribute to bone remodelling. Materials and methods We established orthodontic tooth movement (OTM) model to assess the bone response for mechanical force. The transgenic mice were utilized to label and inhibit Gli1+ cells, respectively. Additionally, mice that conditional ablate Yes-associated protein (Yap) in Gli1+ cells were applied in the present study. The tooth movement and bone remodelling were analysed. Results We first found Gli1+ cells expressed in periodontal ligament (PDL). They were proliferated and differentiated into osteoblastic cells under tensile force. Next, both pharmacological and genetic Gli1 inhibition models were utilized to confirm that inhibition of Gli1+ cells led to arrest of bone remodelling. Furthermore, immunofluorescence staining identified classical mechanotransduction factor Yap expressed in Gli1+ cells and decreased after suppression of Gli1+ cells. Additionally, conditional ablation of Yap gene in Gli1+ cells inhibited the bone remodelling as well, suggesting Gli1+ cells are force-responsive cells. Conclusions Our findings highlighted that Gli1+ cells in PDL directly respond to orthodontic force and further mediate bone remodelling, thus providing novel functional evidence in the mechanism of bone remodelling and first uncovering the mechanical responsive property of Gli1+ cells.

Non‐small–cell lung cancer (NSCLC) is one of the most prevalent type of lung cancers with an increased mortality rate in both developed and developing countries worldwide. Dieckol is one such polyphenolic drug extracted from brown algae which has proven antioxidant and anti‐inflammatory properties. In the present study, we evaluated the anticancer property of dieckol against NSCLC cell line A549. The LC50 value of dieckol was found to be 25 µg/mL by performing 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and the antiapoptotic property of dieckol was analyzed by dual staining technique with acridine orange/propidium iodide (AO/PI) stains. It was further confirmed with flow cytometry analysis with Annexin FITC and JC‐1 staining and the anti‐invasive property was assessed by Transwell assay. The molecular mechanism of dieckol anticancer activity was confirmed by estimating the levels of caspases and by estimating the signaling proteins of Pi3K/AKT/mTOR signaling pathway using the immunoblotting technique. Our data suggest that dieckol is potent anticancer agent, it effectively inhibits the invasive and migratory property A549 cells and it also induces apoptosis via inhibiting Pi3K/AKT/mTOR signaling, activating the tumor suppressor protein E‐cadherin signifying that dieckol is potent natural anticancer drug to treat NSCLC.

Sensitive stigma has been recognized to facilitate outcrossing. We hypothesized that species with different levels of sensitivity might have corresponding differences in components of their breeding system. In this study, three Mazus species with bilobed stigmas were used to test the hypothesis. We explored stigma behaviors of the species in reaction time, recovery time, permanent closing time, and the minimum pollen load causing permanent closure. We investigated floral traits, pollinator type and behavior, pollination intensity, and natural schedule of pollen deposition on stigma. Moreover, we evaluated the mating system of the species by checking seed set after controlled pollination treatments, namely, natural flowers with open pollination, enclosed flowers without pollination, and enclosed flowers with self and outcross hand pollination. Results indicated that stigma of M. pumilus (N. L. Burman) Steenis was not sensitive, whereas stigmas of M. miquelii Makino and M. stachydifolius (Turcz.) Maxim. closed and reopened quickly in response to pollination. Accordingly, hand pollination treatments revealed that seed set of self-spontaneous pollination in M. pumilus was similar to the other treatments. For M. miquelii, outcross pollen resulted in significantly higher seed set than self-pollen. Mazus stachydifolius was self-incompatible. Additionally, the corresponding characteristics in other components of the breeding system for each species were found. Our study indicated that the sensitivity of bilobed stigma might be linked with floral traits and the mating system in a given species. Sensitive stigma should be regarded as an evolutionary mechanism for enhancement of outcrossing.

Malignant mesothelioma (MM) is a highly invasive and chemoresistant malignancy induced by asbestos fibers. NK4, a hepatocyte growth factor antagonist and angiogenesis inhibitor, consists of the N-terminal hairpin domain and four kringle domains of the α-chain of hepatocyte growth factor. The therapeutic potential of NK4 has been demonstrated in a variety of tumor types. However, the mechanisms by which NK4 inhibits tumor growth have not been well delineated. In this study, it is shown that the NK4 adenovirus (Ad-NK4) potently inhibits cell viability, invasiveness and tumorigenicity of human MM cells. Significantly, this study demonstrates for the first time that Ad-NK4 inhibits cancer stem-like cell (CSC) properties as assessed by spheroid formation assay, side population analysis and flow cytometric sorting of CD24 cells. In addition to inhibiting phosphorylation of Met and AKT, Ad-NK4 markedly suppressed the active form of β-catenin, a key mediator of both Wnt and AKT pathways. It is further demonstrated that expression of NK4 suppresses β-catenin nuclear localization and transcriptional activity. Intriguingly, the expression levels of Oct4 and Myc, two critical stem cell factors and downstream targets of β-catenin, were also diminished by Ad-NK4. Furthermore, the strong antitumor effect of NK4 was found to be linked to its ability to inhibit CSCs as revealed by immunohistochemical examination of tumor specimens from a mouse xenograft model of human MM. These findings suggest that NK4 acts as a CSC inhibitor by impeding Met/AKT/β-catenin signaling and holds promise for achieving durable therapeutic responses in MM by constraining the CSC component of these aggressive tumors.

This study explored the effect of deltamethrin, a pesticide, on free Ca 2+ concentration [Ca 2+ ] i , viability, and apoptosis in Madin–Darby canine kidney (MDCK) canine renal tubular cells. Deltamethrin at concentrations between 10μM and 40μM evoked [Ca 2+ ] i rises in a concentration-dependent manner. The Ca 2+ entry was inhibited by nifedipine, econazole, phorbol 12-myristate 13-acetate, and SKF96365. Treatment with the endoplasmic reticulum Ca 2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) in a Ca 2+ -free medium abolished deltamethrin-induced [Ca 2+ ] i rise. Treatment with deltamethrin also abolished BHQ-induced [Ca 2+ ] i rise. Inhibition of phospholipase C (PLC) activity with U73122 abolished deltamethrin-evoked [Ca 2+ ] i rise. Deltamethrin killed cells at 30–60μM in a concentration-dependent manner. The cytotoxic effect of deltamethrin was not reversed by prechelating cytosolic Ca 2+ with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane- N , N , N ′, N ′-tetraacetic acid. Annexin V/propidium iodide staining data suggest that 30–50μM deltamethrin induced apoptosis. Together, in MDCK renal tubular cells, deltamethrin induced [Ca 2+ ] i rises that involved Ca 2+ entry through protein kinase C-mediated store-operated Ca 2+ channels, and PLC-dependent Ca 2+ release from the endoplasmic reticulum. Deltamethrin also induced Ca 2+ -independent cell death that might involve apoptosis.

Finding optimal parameters for simulating biological systems is usually a very difficult and expensive task in systems biology. Brute force searching is infeasible in practice because of the huge (often infinite) search space. In this article, we propose predicting the parameters efficiently by learning the relationship between system outputs and parameters using regression. However, the conventional parametric regression models suffer from two issues, thus are not applicable to this problem. First, restricting the regression function as a certain fixed type (e.g. linear, polynomial, etc.) introduces too strong assumptions that reduce the model flexibility. Second, conventional regression models fail to take into account the fact that a fixed parameter value may correspond to multiple different outputs due to the stochastic nature of most biological simulations, and the existence of a potentially large number of other factors that affect the simulation outputs. We propose a novel approach based on a Gaussian process model that addresses the two issues jointly. We apply our approach to a tumor vessel growth model and the feedback Wright–Fisher model. The experimental results show that our method can predict the parameter values of both of the two models with high accuracy. © 2012 Wiley Periodicals, Inc. Statistical Analysis and Data Mining, 2012 © 2012 Wiley Periodicals, Inc.

Tooth dilaceration refers to a dental anomaly characterized by an abrupt deviation in the longitudinal axis of tooth. Crown-root dilaceration is diagnosed in teeth with sharp angles at the cement-enamel junction. The greater the bending degree is, the less chance there is for successful teeth preservation and relocation. In this report, a clinical case of an impacted maxillary central incisor with severe crown-root dilacerations was described by means of an operative evaluation using three-dimensional dental computed tomography and a multidisciplinary approach that included surgical, orthodontic, endodontic, prosthetic and periodontal therapy.

Limitations of current regeneration modalities underscore the importance of restoring the three-dimensional (3D) microenvironment of periodontal development, which is able to elicit the intrinsic capacity of mesenchymal stem cells to proceed to engage in a redevelopment-like program. With increased attention for the potential therapeutic applications of periodontal ligament stem cells (PDLSCs) in periodontal regeneration, it has been proposed that bone marrow mesenchymal stem cells (BMMSCs) are very likely another cell source of physiological repair of periodontal tissues. With this in mind, enlightened from the research targeting the fabrication of laminar structures such as liver and kidney with heterotypic stratification of cell sheets, we proposed a novel possible strategy based on self-assembly approach, which is akin to the physiological phenomenon that occurs during organogenesis, to enhance complete reconstruction of functional complex periodontium-organ systems. We assumed that in this strategy, using the intrinsic capacity of monodispersed cells to self-assemble into a microtissue such as a 3D spheroid, bilayered cell pellet constructs comprising calcified bone-forming cell pellets (i.e., BMMSCs) and cementum/PDL-forming cell pellets (i.e., PDLSCs) would be fabricated in vitro in a tissue-mimicking way and then implanted into periodontal defects. We hypothesize that this novel strategy might open new options to reconstruct extended periodontal defects and then achieve the ultimate goal of predictable and complete regeneration of the periodontium.

Background and Objective: Mammalian tooth root development is a long-term process during which root elongates along the apical direction and is accompanied with the formation of periodontium. Considering the heterogeneous apical region of developing root as a functional entity, we observed and characterized the developing apical complex of rat molar root. The aim of the present study was to investigate the characteristics and developmental capability of developing apical complex in situ and in vitro. Material and Methods: Histological analysis of rat developing apical complex was performed using hematoxylin and eosin staining and immunohistochemical staining. Cell counting, bromodeoxyuridine incorporation, flow cytometry assays and western blot analyses were performed to assess the proliferation potential of developing apical complex cells in vitro, and its mineralization potential was investigated by alkaline phosphatase activity, alizarin red staining and reverse transcription–polymerase chain reaction analysis. In vivo transplantation of both developing apical complex tissues and cells were used to characterize the differentiation capacity of developing apical complex cells. Dental pulp cells were used as a control in this study. Results: Isolated developing apical complex maintained the developmental capability to form tooth root/periodontal complex ectopically. Developing apical complex cells exhibited relatively higher proliferation and mineralization potential compared with dental pulp cells in culture. When cultured developing apical complex cells were putatively depleted of Hertwig’s epithelial root sheath cells, only osteodentin-like tissues and fibrous connective tissues formed in cell-scaffold explants. Conclusion: The sustainable development ability of developing apical complex qualifies it as the growth center of tooth root and as a promising candidate source of cells for tooth root and periodontal regeneration.

Pro-inflammatory N1 and anti-inflammatory N2 neutrophil subtypes have recently been described in stroke. The objective of the current study was to investigate the temporal neutrophil polarization f...

A new type of boron-nitrogen-midified fatty acid as a water-based lubricant additive was prepared and the chemical structure characterised by infrared spectroscopy. The tribological properties of the additive in water were evaluated using friction testers. The morphologies and tribochemical species of worn surfaces were analysed by means of X-ray photoelectron spectroscopy (XPS). The results show that the additive is very good at increasing the losdcarrying capacity and the antiwear and friction-reducing properties of wter. A lubrication mechanism is inferred in which a lhigh-strength adsorption film and a tribochemical reaction film form on the rubbing surfaces as a resuly of the carrier effect of long-chain fatty acid molecules, the high reaction activities of nitrogen, and the electron deficiency of boron, as well as the interactions of these factors.

A modified finite-difference time-domain (FDTD) method, called generalized total-field/scattered-field (G-TF/SF) FDTD, is applied to compute the interconnect response on an infinite dielectric substrate illuminated by an external electromagnetic field. This method is also extended form 2D to 3D. The current distributions on the strips obtained by using the 3D G-FDTD method are presented and are in good agreement with the results computed via the method of moments (MoM). The simulation results indicate that this method is efficient and accurate for the modeling of an infinite scatterer problem with a compact FDTD grid. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 42: 304–307, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20286