Several human cancers have been found to contain cancer stem-like cells (CSCs) having cancer-initiating ability. However, only a few reports have shown the existence of CSCs in bone and soft tissue ...sarcomas. In this study, we identified and characterised side population (SP) cells that showed drug-resistant features in human bone sarcoma cell lines.
In seven osteosarcoma cell lines (OS2000, KIKU, NY, Huo9, HOS, U2OS and Saos2) and in one bone malignant fibrous histiocytoma (MFH) cell line (MFH2003), the frequency of SP cells was analysed. Tumourigenicity of SP cells was assessed in vitro and in vivo. Gene profiles of SP cells and other populations (main population; MP) of cells were characterised using cDNA microarrays.
SP cells were found in NY (0.31%) and MFH2003 (5.28%). SP cells of MFH2003 formed spherical colonies and re-populated into SP and MP cells. In an NOD/SCID mice xenograft model, 1 x 10(3) sorted SP cell-induced tumourigenesis. cDNA microarray analysis showed that 23 genes were upregulated in SP cells.
We showed that SP cells existed in bone sarcoma cell lines. SP cells of MFH2003 had cancer-initiating ability in vitro and in vivo. The gene profiles of SP cells could serve as candidate markers for CSCs in bone sarcomas.
Double Shockley-type stacking faults (2SSFs) formed in 4H-SiC epitaxial films with a dopant concentration of 1.0 × 1016 cm−3 were characterized using grazing incident X-ray topography and ...high-resolution scanning transmission electron microscopy. The origins of 2SSFs were investigated, and it was found that 2SSFs in the epitaxial layer originated from narrow SFs with a double Shockley structure in the substrate. Partial dislocations formed between 4H-type and 2SSF were also characterized. The shapes of 2SSFs are related with Burgers vectors and core types of the two Shockley partial dislocations.
The core light-harvesting complexes (LH1) in bacteriochlorophyll (BChl)
b
-containing purple phototrophic bacteria are characterized by a near-infrared absorption maximum around 1010 nm. The ...determinative cause for this ultra-redshift remains unclear. Here, we present results of circular dichroism (CD) and resonance Raman measurements on the purified LH1 complexes in a reaction center-associated form from a mesophilic and a thermophilic
Blastochloris
species. Both the LH1 complexes displayed purely positive CD signals for their Q
y
transitions, in contrast to those of BChl
a
-containing LH1 complexes. This may reflect differences in the conjugation system of the bacteriochlorin between BChl
b
and BChl
a
and/or the differences in the pigment organization between the BChl
b
- and BChl
a
-containing LH1 complexes. Resonance Raman spectroscopy revealed remarkably large redshifts of the Raman bands for the BChl
b
C3-acetyl group, indicating unusually strong hydrogen bonds formed with LH1 polypeptides, results that were verified by a published structure. A linear correlation was found between the redshift of the Raman band for the BChl C3-acetyl group and the change in LH1-Q
y
transition for all native BChl
a
- and BChl
b
-containing LH1 complexes examined. The strong hydrogen bonding and π–π interactions between BChl
b
and nearby aromatic residues in the LH1 polypeptides, along with the CD results, provide crucial insights into the spectral and structural origins for the ultra-redshift of the long-wavelength absorption maximum of BChl
b
-containing phototrophs.
Our recent studies demonstrated that regional bone loss in the unloaded hind limbs of tail-suspended mice triggered pain-like behaviors due to the acidic environment in the bone induced by osteoclast ...activation. The aims of the present study were to examine whether TRPV1, ASIC and P2X (known as nociceptors) are expressed in bone, and whether the antagonists to those receptors affect the expression of osteoblast and osteoclast regulators, and prevent the triggering of not only pain-like behaviors but also high bone turnover conditions in tail-suspension model mice.
The hind limb-unloaded mice were subjected to tail suspension with the hind limbs elevated for 14days. The effects of the TRPV1, ASIC3, P2X2/3 antagonists on pain-like behaviors as assessed by the von Frey test, paw flick test and spontaneous pain scale; the expressions of TRPV1, ASICs, and P2X2 in the bone; and the effects of those antagonists on osteoblast and osteoclast regulators were examined. In addition, we evaluated the preventive effect of continuous treatment with a TRPV1 antagonist on the trigger for pain-like behavior and bone loss in tail-suspended mice.
Pain-like behaviors were significantly improved by the treatment with TRPV1, ASIC, P2X antagonists; TRPV1, ASICs and P2X were expressed in the bone tissues; and the antagonists to these receptors down-regulated the expression of osteoblast and osteoclast regulators in tail-suspended mice. In addition, continuous treatment with a TRPV1 antagonist during tail-suspension prevented the induction of pain-like behaviors and regional bone loss in the unloaded hind limbs.
We, therefore, believe that those receptor antagonists have a potential role in preventing the triggering of skeletal pain with associated regional bone metabolic disorder.
•Bone loss in tail-suspended mice was related to induction of pain-like behaviors.•TRPV1, ASIC and P2X, known as nociceptors, were expressed in bone.•Antagonist to TRPV1, ASIC and P2X improved pain-like behavior in tail-suspended mice.•Antagonist to TRPV1, ASIC and P2X inhibited expression of regulators of bone cells.•Treatment with TRPV1 antagonist prevented regional bone loss in unloaded hind limbs.
Summary
Background
LL‐37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis ...(SSc).
Objectives
To elucidate the potential role of LL‐37 in SSc.
Methods
The expression of target molecules was evaluated by immunostaining and quantitative reverse‐transcription real‐time polymerase chain reaction in human and murine skin. The mechanisms regulating LL‐37 expression in endothelial cells were examined by gene silencing and chromatin immunoprecipitation. Serum LL‐37 levels were determined by enzyme‐linked immunosorbent assay.
Results
In SSc lesional skin, LL‐37 expression was increased in dermal fibroblasts, perivascular inflammatory cells, keratinocytes and, particularly, dermal small vessels. Expression positively correlated with interferon‐α expression, possibly reflecting LL‐37‐dependent induction of interferon‐α. In SSc animal models, bleomycin‐treated skin exhibited the expression pattern of CRAMP, a murine homologue of LL‐37, similar to that of LL‐37 in SSc lesional skin. Furthermore, Fli1+/− mice showed upregulated expression of CRAMP in dermal small vessels. Fli1 binding to the CAMP (LL‐37 gene) promoter and Fli1 deficiency‐dependent induction of LL‐37 were also confirmed in human dermal microvascular endothelial cells. In the analysis of sera, patients with SSc had serum LL‐37 levels significantly higher than in healthy controls. Furthermore, serum LL‐37 levels positively correlated with skin score and the activity of alveolitis and were significantly elevated in patients with digital ulcers compared with those without.
Conclusions
LL‐37 upregulation, induced by Fli1 deficiency at least in endothelial cells, potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in SSc.
What's already known about this topic?
LL‐37, an antimicrobial peptide, has been shown to be upregulated in systemic sclerosis dermal fibroblasts.
LL‐37 potentially contributes to dermal fibrosis through its antiapoptotic effect on those cells.
What does this study add?
LL‐37 potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in systemic sclerosis.
This further supports the critical role of antimicrobial peptides in the development of autoimmune and inflammatory diseases.
What is the translational message?
LL‐37 induction due to Fli1 deficiency in endothelial cells supports the notion that Fli1 deficiency is a key predisposing factor in the pathogenesis of systemic sclerosis.
This has recently been demonstrated by the establishment of a new systemic sclerosis animal model, with mice double heterozygous for the Klf5 and Fli1 genes.
Familial amyloid polyneuropathy (FAP), which is a fatal disorder inherited in an autosomal dominant fashion, is characterized by systemic accumulation of polymerized transthyretin (TTR) in the ...peripheral nerves and systemic organs. Liver transplantation has become an accepted treatment of this disorder because it stops the major production of amyloidogenic TTR. However, improved survival of transplant patients compared with that of nontransplant patients has not been sufficiently demonstrated. This study investigated whether transplantation improved the long-term outcome of patients by comparing the survival of patients who had transplantations with that of patients who had not had transplantations.
Eighty consecutive patients with FAP Val30Met who visited Kumamoto University Hospital between January 1990 and December 2010 were studied. The transplant group consisted of 37 patients who had a partial hepatic graft via living donor transplantation in Japan or who underwent liver transplantation in Sweden, Australia, or the United States. The nontransplant group consisted of 43 patients with FAP. Survival was evaluated by using Kaplan-Meier analysis, and the difference in survival was examined via the log-rank test.
The transplant group had prolonged survival (p < 0.001) compared with the nontransplant group. The estimated probability of survival at 10 years was 56.1% for the nontransplant group vs 100% for the transplant group.
Liver transplantation should be considered as an effective treatment in clinical management of patients with FAP Val30Met.
This study provides Class III evidence that liver transplantation prolongs survival in patients with FAP Val30Met.
Abstract
We present 0.97 × 0.53 arcsec2 (470 pc × 250 pc) resolution CO (J = 2–1) observations towards the nearby luminous merging galaxy NGC 6240 with the Atacama Large Millimeter/submillimeter ...Array. We confirmed a strong CO concentration within the central 700 pc, which peaks between the double nuclei, surrounded by extended CO features along the optical dust lanes (∼11 kpc). We found that the CO emission around the central, a few kpc, has extremely broad velocity wings with full width at zero intensity ∼ 2000 km s−1, suggesting a possible signature of molecular outflow(s). In order to extract and visualize the high-velocity components in NGC 6240, we performed a multiple Gaussian fit to the CO data cube. The distribution of the broad CO components shows four extremely large line width regions (∼1000 km s−1) located 1–2 kpc away from both nuclei. Spatial coincidence of the large line width regions with H α, near-IR H2, and X-ray suggests that the broad CO (2–1) components are associated with nuclear outflows launched from the double nuclei.
Detection of drug-target proteins and biomarkers that are expressed in cancer tissue has significant potential for both diagnosis and treatment of cancer. However, current immuno-histochemical and ...cytogenetic analyses of biopsy specimens for pre-operational diagnosis are highly invasive
and often difficult to apply to lung cancer patients. The purpose of this study was to evaluate the possible utility of determining epidermal growth factor receptor (EGFR) expression on exosomal membranes using a targeted ELISA with an anti-CD81 antibody as a capture antibody for lung cancer
diagnosis. While soluble EGFR (sEGFR) levels in plasma were not remarkably different between lung cancer patients and normal controls, significantly higher exosomal EGFR expression levels were observed in 5/9 cancer cases compared to normal controls. These results suggest that measurement
of exosomal protein levels could be useful for in vitro diagnosis, and that exosomal EGFR is a possible biomarker for characterization of lung cancer.
Recently, it has been shown that large stacks of intrinsic Josephson junctions in Bi2Sr2CaCu2O8 emit synchronous THz radiation, the synchronization presumably triggered by a cavity resonance. To ...investigate this effect we use low temperature scanning laser microscopy to image electric field distributions. We verify the appearance of cavity modes at low bias and in the high input-power regime we find that standing-wave patterns are created through interactions with a hot spot, possibly pointing to a new mode of generating synchronized radiation in intrinsic Josephson junction stacks.
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