Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease that affects both cartilage and subchondral bone. We used microarray to identify changes in gene expression levels in the TMJ ...during early stages of the disease, using an established TMJ OA genetic mouse model deficient in 2 extracellular matrix proteins, biglycan and fibromodulin (bgn-/0fmod-/-). Differential gene expression analysis was performed with RNA extracted from 3-week-old WT and bgn-/0fmod-/- TMJs with an intact cartilage/subchondral bone interface. In total, 22 genes were differentially expressed in bgn-/0fmod-/- TMJs, including 5 genes involved in osteoclast activity/differentiation. The number of TRAP-positive cells were three-fold higher in bgn-/0fmod-/- TMJs than in WT. Quantitative RT-PCR showed up-regulation of RANKL and OPG, with a 128% increase in RANKL/OPG ratio in bgn-/0fmod-/- TMJs. Histology and immunohistochemistry revealed tissue disorganization and reduced type I collagen in bgn-/0fmod-/- TMJ subchondral bone. Early changes in gene expression and tissue defects in young bgn-/0fmod-/- TMJ subchondral bone are likely attributed to increased osteoclast activity. Analysis of these data shows that biglycan and fibromodulin are critical for TMJ subchondral bone integrity and reveal a potential role for TMJ subchondral bone turnover during the initial early stages of TMJ OA disease in this model.
Methotrexate (MTX)-induced intestinal mucosal injury in animals has been studied to understand how MTX can cause gastrointestinal disorders, but the pathogenesis of gastrointestinal disorders is ...still uncertain. We have attempted to reveal how dietary factors influence intestinal toxicity due to MTX. Mice were fed normal chow (NC) or a high-fat high-sucrose diet (HFHSD) before oral administration of MTX. While MTX significantly decreased the survival rates of mice fed HFHSD, the intestinal epithelial injury was detected. MTX excretion in the feces of mice fed HFHSD was reduced. Change of diets between NC and HFHSD influences the survival. The survival rates of the mice fed a high-sucrose diet or control diet were higher than those fed HFHSD. Higher survival rates were observed in mice fed a high-fat high-sucrose diet modified (HFHSD-M) in which casein was replaced by soybean-derived proteins. The survival rates of mice treated with vancomycin were lower than those administered neomycin. Microbiome and metabolome analyses on feces suggest a similarity of the intestinal environments of mice fed NC and HFHSD-M. HFHSD may modify MTX-induced toxicity in intestinal epithelia on account of an altered MTX distribution as a result of change in the intestinal environment.
Context. The remnants of core-collapse supernovae (SNe) are probes of the physical processes associated with their parent SNe. Aims. Here we aim to explore to which extent the remnant keeps memory of ...the asymmetries that develop stochastically in the neutrino-heating layer due to hydrodynamic instabilities (e.g., convective overturn and the standing accretion shock instability; SASI) during the first second after core bounce. Methods. We coupled a three-dimensional (3D) hydrodynamic model of a neutrino-driven SN explosion, which has the potential to reproduce the observed morphology of the Cassiopeia A (Cas A) remnant, with 3D (magneto)-hydrodynamic simulations of the remnant formation. The simulations cover ≈2000 yr of expansion and include all physical processes relevant to describe the complexities in the SN evolution and the subsequent interaction of the stellar debris with the wind of the progenitor star. Results. The interaction of large-scale asymmetries left from the earliest phases of the explosion with the reverse shock produces, at the age of ≈350 yr, an ejecta structure and a remnant morphology which are remarkably similar to those observed in Cas A. Small-scale structures in the large-scale Fe-rich plumes that were created during the initial stages of the SN, combined with hydrodynamic instabilities that develop after the passage of the reverse shock, naturally produce a pattern of ring- and crown-like structures of shocked ejecta. The consequence is a spatial inversion of the ejecta layers with Si-rich ejecta being physically interior to Fe-rich ejecta. The full-fledged remnant shows voids and cavities in the innermost unshocked ejecta, which are physically connected with ring-like features of shocked ejecta in the main shell in most cases, resulting from the expansion of Fe-rich plumes and their inflation due to the decay of radioactive species. The asymmetric distributions of 44Ti and 56Fe, which are mostly concentrated in the northern hemisphere, and pointing opposite to the kick velocity of the neutron star, as well as their abundance ratio are both compatible with those inferred from high-energy observations of Chandra and NuSTAR. Finally, the simulations show that the fingerprints of the SN can still be visible ≈2000 yr after the explosion. Conclusions. The main asymmetries and features observed in the ejecta distribution of Cas A can be explained by the interaction of the reverse shock with the initial large-scale asymmetries that developed from stochastic processes (e.g., convective overturn and SASI activity) that originate during the first seconds of the SN blast.
Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of ...angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension.
Transforming growth factor-β (TGF-β) is a major inducer of epithelial-mesenchymal transition (EMT) in different cell types. TGF-β-mediated EMT is thought to contribute to tumour cell spread and ...metastasis. Sialyl Lewis antigens synthesised by fucosyltransferase (FUT) 3 and FUT6 are highly expressed in patients with metastatic colorectal cancer (CRC) and are utilised as tumour markers for cancer detection and evaluation of treatment efficacy. However, the role of FUT3 and FUT6 in augmenting the malignant potential of CRC induced by TGF-β is unclear.
Colorectal cancer cell lines were transfected with siRNAs for FUT3/6 and were examined by cell proliferation, invasion and migration assays. The expression and phosphorylation status of TGF-β downstream molecules were analysed by western blot. Fucosylation of TGF-β receptor (TβR) was examined by lectin blot analysis.
Inhibition of FUT3/6 expression by siRNAs suppressed the fucosylation of type I TβR and phosphorylation of the downstream molecules, thereby inhibiting the invasion and migration of CRC cells by EMT.
Fucosyltransferase 3/6 has an essential role in cancer cell adhesion to endothelial cells by upregulation of sialyl Lewis antigens and also by enhancement of cancer cell migration through TGF-β-mediated EMT.
In patients awaiting LuTx, MV and ECMO are often the last ways to create a bridge to LuTx. Both interventions are associated with a poor posttransplant outcome and survival rate. To improve the ...results of these patients, new “bridging‐strategies” are necessary. Recent reports demonstrate promising results for the concept of “awake ECMO” in adult patients. To date, no data on this approach in pediatric patients have been available. We therefore describe the use of VV‐ECMO as a treatment strategy for RF in awake pediatric patients. It presents our experiences with the first three children treated using this new concept. Mean amount of time on ECMO was 44 days (range, 11.5–109 days). Two patients were successfully bridged to their LuTx. Both are still alive without any recurrences (24 and three months following LuTx). One patient died before a further LuTx after 109 days on ECMO due to adenoviral infection. Although reintubation was necessary in two patients, and total time being awake while on ECMO was <50%, we conclude that the concept of “awake VV‐ECMO” is feasible for the treatment of RF and can be used as a “bridging therapy” to LuTx.
Bone marrow–derived mesenchymal stem/progenitor cells (BMSCs) are commonly used in regeneration therapy. The current primary source of BMSCs is the iliac crest; however, the procedure is associated ...with various burdens on the patient, including the risk of pain and infection. Hence, the possibility to collect BMSCs from other, more accessible, sources would be an attractive approach. It is well known that stem cells migrate from surrounding tissues and play important roles in wound healing. We thus hypothesized that stem/progenitor cells could be isolated from granulation tissue in the dental socket, and we subsequently collected granulation tissue from dog dental socket 3 d after tooth extraction. After enzyme digestion of the collected tissue, the cells forming colonies constituted the dental socket–derived stem/progenitor cells (dDSCs). Next, dDSCs were compared with dog BMSCs (dBMSCs) for phenotype characterization. A flow cytometric analysis showed that dDSCs were positive for CD44, CD90, and CD271 but negative for CD34 and CD45, similar to dBMSCs. dDSCs also exhibited osteogenic, adipogenic, and chondrogenic differentiation ability, similar to dBMSCs, with a higher capacity for colony formation, proliferation, and motility than dBMSCs. In addition, an in vivo ectopic bone formation assay showed that dDSCs and dBMSCs both induced hard tissue formation, although only dDSCs formed a fibrous tissue-like structure connected to the newly formed bone. Finally, we tested the ability of dDSCs to regenerate periodontal tissue in a one-wall defect model. The defects in the dDSC-transplanted group (β-TCP/PGA/dDSCs) were regenerated with cementum-like and periodontal ligament-like tissues and alveolar bone, whereas only bony tissue was observed in the control group (β-TCP/PGA). In conclusion, we identified and characterized a population of stem/progenitor cells in granulation tissue obtained from the dental socket that exhibited several characteristics similar to those of BMSCs. Dental sockets could therefore be a novel source for isolating stem/progenitor cells from bone.
We demonstrate the ultrafast photoinduced Mott transition from a charge transfer insulator to a metal in a halogen-bridged Ni-chain compound by pump-probe reflection spectroscopy. Upon the ...irradiation of a 130-femtosecond laser pulse, the spectral weight of the gap transition is transferred to the inner-gap region. When the photoexcitation density exceeds 0.1/Ni site, the Drude-like high-reflection band appears in the infrared region, signaling the formation of a metallic state. The photogeneration of the metallic state and the subsequent recovery to the original gapped state occur within a few picoseconds.
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