Essentials
The role of C‐type lectin‐like receptor‐2 (CLEC‐2) in cancer progression is unclear.
CLEC‐2‐depleted mouse model is generated by using a rat anti‐mouse CLEC‐2 monoclonal antibody.
CLEC‐2 ...depletion inhibits hematogenous tumor metastasis of podoplanin‐expressing B16F10 cells.
CLEC‐2 depletion prolongs cancer survival by suppressing thrombosis and inflammation.
Summary
Background
C‐type lectin‐like receptor 2 (CLEC‐2) is a platelet activation receptor of sialoglycoprotein podoplanin, which is expressed on the surface of certain types of tumor cells. CLEC‐2–podoplanin interactions facilitate hematogenous tumor metastasis. However, direct evidence of the role of CLEC‐2 in hematogenous metastasis and cancer progression is lacking.
Objective and methods
We generated immunological CLEC‐2‐depleted mice by using anti‐mouse CLEC‐2 monoclonal antibody 2A2B10 and investigated whether CLEC‐2 promoted hematogenous tumor metastasis and tumor growth and exacerbated the prognosis of mice bearing podoplanin‐expressing B16F10 melanoma cells.
Results
Our results showed that hematogenous metastasis was significantly inhibited in CLEC‐2‐depleted mice. B16F10 cells co‐cultured with wild‐type platelets, but not with CLEC‐2‐deficient platelets, showed increased proliferation. However, B16F10 cell proliferation was not inhibited in CLEC‐2‐depleted mice. Histological analysis showed that thrombus formation in tumor vessels was significantly inhibited and functional vessel density was significantly increased in CLEC‐2‐depleted mice. These data suggest that CLEC‐2 deficiency may inhibit thrombus formation in tumor vessels and increase the density of functional vessels, thus improving oxygen and nutrient supply to tumors, indirectly promoting tumor proliferation. Furthermore, the overall survival of CLEC‐2‐depleted mice was significantly prolonged, which may be due to the suppression of thrombus formation in the lungs and subsequent inhibition of systemic inflammation and cachexia.
Conclusions
These data provide a rationale for the targeted inhibition of CLEC‐2 as a new strategy for preventing hematogenous tumor metastasis and for inhibiting cancer‐related thromboembolism.
We have established a method for the preparation of Pt nanoparticles (NPs) with a series of target mean-diameters (dm) and sharp size-distribution, supported on graphitized carbon black (GCB), ...Pt/GCB, without changing the mean interparticle distances (dPt-Pt), on GCB surfaces. This is achieved by the deposition of additional Pt-skin layer(s) on the NPs surfaces of the core Pt/GCB from its suspending aqueous solution, which contains precise amounts of Pt-complex equivalent to the projected thickness of Pt skin-layer(s), by simple bubbling of hydrogen, where the core Pt/GCB was prepared by the nanocapsule method that is able to provide NPs with highly uniform dispersion on the support with an extremely narrow size distribution. Contrary to the common view, we were able to demonstrate a lack of dependence of the long-term stability on the particle size of Pt NPs (dm<5nm) using test protocols for monitoring the load-change cycling and start/stop operation of polymer electrolyte fuel cells (PEFCs) at 65°C. This finding is evidence that the so-called “particle size effect” on the stability is not intrinsic but avoidable for the NP catalysts, in addition to our previous demonstration of the independence of the initial specific activity upon Pt NPs sizes for the oxygen electroreduction. This deviation from “common-sense,” i.e., the improvement of the activity and stability at Pt NPs by means of the sharp size distribution and their uniform dispersion on the GCB support, becomes extremely important as a guiding principle to develop cathode catalysts for practical PEFCs. The present unique achievement of the durability is probably brought about by the mitigation of nonuniform growth of Pt NPs via Ostwald ripening. This is most likely due to the uniform Pt dissolution/re-deposition among the uniformly sized and distributed nanoparticles.
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•Management of both high activity & durability at Pt nanocatalysts for fuel cells.•No particle size effects appear on Pt nanoparticle (NP) activity & durability.•Such properties are confirmed with durability test protocols for fuel cell vehicles.•Uniform NP size & dispersion on supports realize such distinctive properties.•We propose a facile preparation of such catalysts to suppress Ostwald ripening.
Highlights ► Epigenetic gene regulation plays a critical role in neuropathic pain. ► Initial anti-BDNF antibody treatment blocks the development of neuropathic pain. ► Injury initially induces BDNF ...expression in the spinal dorsal horn and DRG. ► BDNF exon I transcript is responsive to injury in the DRG. ► Injury initially up-regulates histone H3 and H4 acetylation at BDNF promoter I.
Abstract Objectives The aim of the study is to determine factors affecting ischaemic wound healing and role of the angiosome concept in bypass surgery. Design Single-centre, retrospective clinical ...study. Materials and methods A total of 249 consecutive critical ischaemic limbs with tissue loss in 228 patients who underwent distal bypasses from 2003 to 2009 were reviewed. A total of 81% of patients were diabetic, and 49% of patients had dialysis-dependent renal disease (end-stage renal disease, ESRD). Distal targets of bypasses were the crural artery (57%) and the pedal artery (43%). Results The complete healing of ischaemic wounds was achieved in 211 limbs (84.7%). ESRD (odds ratio (OR) 0.127, p < 0.001), diabetes (OR 0.216, p = 0.030), Rutherford category 6 (R6) with heel ulcer/gangrene (OR 0.134, p < 0.001), R6 except heel (OR 0.336, p = 0.025) and low albuminaemia (OR 0.387, p = 0.049) were negative predictors of wound healing. Regarding the angiosome, the healing rate in the indirect revascularisation (IR) group was slower than in the direct revascularisation (DR) group, especially in patients with ESRD ( p < 0.001). However, the healing rates of the DR and IR groups were similar after minimising background differences with propensity score methods ( p = 0.185). Conclusions In the field of bypass surgery, the angiosome concept seems unimportant, at least in non-ESRD cases. The location and extent of ischaemic wounds as well as co-morbidities may be more relevant than the angiosome in terms of wound healing.
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•H2 evolution activities at Pt-skin/Pt3Co single crystal electrodes were examined.•H2 evolution activity increased in the order Pt-skin/Pt3Co(1 0 0) < (1 1 1) < (1 1 0).•The Tafel ...slope of Pt-skin/Pt3Co(1 1 0) was appreciably smaller than that of Pt(1 1 0).•The adsorption energies for hydrogen atoms decreased on Pt-skin/Pt3Co(1 1 1).
We have examined for the first time the hydrogen evolution reaction (HER) activity at the (111), (100), and (110) faces of well-defined Pt-skin/Pt3Co single crystal electrodes in H2-saturated 0.1 M HClO4 solution in order to clarify the mechanism for the increased HER activities at Pt-skin/Pt-M (M = Co, Fe) nanoparticles dispersed on a carbon support, which we recently developed as highly active cathode catalysts for proton exchange membrane electrolyte water electrolysis. The HER current densities at −0.02 V vs. RHE for the Pt-skin/Pt3Co single crystal rotating disk electrodes increased in the order (100) < (111) < (110), which is identical with that reported for pure Pt single crystal electrodes. Based on density functional theory calculations, the increase in the HER activity is ascribed to the destabilization of the on-top form of adsorbed atomic hydrogen (HOPD), which facilitates the recombination and desorption of two HOPD atoms to produce molecular H2.
We propose a novel scintillation detector design for positron emission tomography (PET), which has depth of interaction (DOI) capability and uses a single-ended readout scheme. The DOI detector ...contains a pair of crystal bars segmented using sub-surface laser engraving (SSLE). The two crystal bars are optically coupled to each other at their top segments and are coupled to two photo-sensors at their bottom segments. Initially, we evaluated the performance of different designs of single crystal bars coupled to photomultiplier tubes at both ends. We found that segmentation by SSLE results in superior performance compared to the conventional method. As the next step, we constructed a crystal unit composed of a 3 × 3 × 20 mm
crystal bar pair, with each bar containing four layers segmented using the SSLE. We measured the DOI performance by changing the optical conditions for the crystal unit. Based on the experimental results, we then assessed the detector performance in terms of the DOI capability by evaluating the position error, energy resolution, and light collection efficiency for various crystal unit designs with different bar sizes and a different number of layers (four to seven layers). DOI encoding with small position error was achieved for crystal units composed of a 3 × 3 × 20 mm
LYSO bar pair having up to seven layers, and with those composed of a 2 × 2 × 20 mm
LYSO bar pair having up to six layers. The energy resolution of the segment in the seven-layer 3 × 3 × 20 mm
crystal bar pair was 9.3%-15.5% for 662 keV gamma-rays, where the segments closer to the photo-sensors provided better energy resolution. SSLE provides high geometrical accuracy at low production cost due to the simplicity of the crystal assembly. Therefore, the proposed DOI detector is expected to be an attractive choice for practical small-bore PET systems dedicated to imaging of the brain, breast, and small animals.
Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option.
To systematically determine the ...effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia.
Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials.
Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome.
Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides.
Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to -3.17 kg (95% CI: -4.44 to -1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids.
When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia.
Objective
Synthetic glucocorticoids cause various psychiatric symptoms. Prescription of psychotropic drugs could be considered to be a proxy for manifestation of psychiatric symptoms. The aim of this ...study was to investigate the prescriptions of psychotropics in outpatients receiving synthetic glucocorticoids.
Methods
We used the claims sampling data during January 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan made by the Ministry of Health, Labor, and Welfare in Japan. We compared the prescription rates of psychotropics between outpatients receiving oral synthetic glucocorticoids and age‐ and sex‐matched controls and the prescription rates of psychotropics among the eight dosage groups of synthetic glucocorticoids by chi‐squared test, and chlorpromazine/imipramine/diazepam equivalent doses (or daily defined doses) of respective psychotropics among these groups using Welch's t‐test.
Results
Synthetic glucocorticoids were prescribed to 3.1% (n = 18 122) of 581 990 patients. The prescription rates of psychotropics were significantly higher among the synthetic glucocorticoid recipients than among the non‐recipients: antipsychotics, 1.8% (n = 321) vs. 1.1% (n = 201) (P = 1.4 × 10−7); antidepressants, 4.0% (n = 724) vs. 2.0% (n = 359) (P = 8.7 × 10−30); anxiolytics/hypnotics, 16.7% (n = 3029) vs. 10.2% (n = 1841) (P = 2.7 × 10−75); and mood stabilizers, 1.3% (n = 238) vs. 0.7% (n = 120) (P = 3.6 × 10−10) respectively. There was no significant difference in the prescription rates of any psychotropic drugs, other than anxiolytics/hypnotics, among the eight synthetic glucocorticoid dosage groups.
Conclusion
Prescriptions of oral synthetic glucocorticoids were found to be associated with the use of any of the types of psychotropic drugs, other than anxiolytics/hypnotics, although a causal relationship could not be confirmed due to the retrospective and cross‐sectional nature of this study.
The anthropogenic CO
accumulating in the ocean is lowering seawater carbonate ion concentration and may reduce calcification rates of marine calcareous organisms. Several proxies based on test ...weights of planktic foraminifera have been used to evaluate the impact of ocean acidification on these organisms. Unfortunately, because of the absence of a method to evaluate the bulk density of a test, the impact of seawater carbonate chemistry on test calcification is still not fully understood. In this study, we measured bulk densities of living Globigerina bulloides (planktic foraminifera) tests with an X-ray micro-computed tomography (XMCT) scanner and compared them with ambient seawater characteristics. Results demonstrated that test bulk densities were controlled by ambient seawater carbonate ion concentrations and that changes of test bulk densities were accompanied by changes in micron to submicron scale porosity of internal ultrastructure. These results suggest that alteration of the bulk density of foraminiferal tests due to acidification of ambient seawater can be directly observed by XMCT scanning. A useful metric of calcification intensity would therefore be physical measurements of test densities with XMCT.
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