Summary Objective The objectives were to investigate the in vivo effects of treatment with rebamipide on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA) ...and to explore its mode of action. Materials and methods OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA). Oral administration of rebamipide was initiated on the day of MIA injection, 3 or 7 days after. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. We analyzed the samples macroscopically and histomorphologically, and used immunohistochemistry to investigate the expression of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), hypoxia-inducible factor-2α (HIF-2α), inducible nitric oxide synthase (iNOS), and nitrotyrosine in knee joints. Real-time quantitative reverse transcription–polymerase chain reaction was used to quantify the mRNA for catabolic and anticatabolic factors in human OA chondrocytes. Results Rebamipide showed an antinociceptive property and attenuated cartilage degeneration. Rebamipide reduced the expression of MMP-13, IL-1β, HIF-2α, iNOS, and nitrotyrosine in OA cartilage in a dose-dependent manner. Nitrotyrosine expression in the subchondral bone region was decreased in the rebamipide-treated joints. mRNA expression of MMP-1, -3, and -13, and ADAMTS5 was attenuated in IL-1β-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of metalloproteinase-1 and -3. Conclusion The results show the inhibitory effects of rebamipide on pain production and cartilage degeneration in experimentally induced OA. The suppression of oxidative damage and the restoration of extracellular matrix homeostasis of articular chondrocyte suggest that rebamipide is a potential therapeutic strategy for OA.
The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 ... GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.
Summary
Background
Aspirin‐intolerant asthma (AIA) refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin or other non‐steroidal ...anti‐inflammatory drugs (NSAIDs). Angiotensin I‐converting enzyme (ACE), a membrane‐bound peptidase present in the lung, plays a pivotal role in the metabolism of the endogenous peptides involved in the pathogenesis of asthma.
Methods
We screened a Korean asthma cohort (581 asthmatics including 81 aspirin‐intolerant asthmatics and 231 aspirin‐tolerant asthmatics, and 181 normal controls) for four single nucleotide polymorphisms (SNPs; −262 A>T and −115 T>C in the 5′‐flanking region and +5467 T>C Pro450Pro and+11860 A>G Thr776Thr in the coding region) and one ins/del (+21288 CT) in the ACE gene.
Results
None of the SNPs or haplotypes showed any association with the development of asthma, but they were significantly associated with the risk of AIA. Logistic regression indicated that the frequency of the rare alleles of −262 A>T and −115 T>C was higher in subjects with AIA than in subjects with aspirin‐tolerant asthma (ATA) (P=0.003–0.01, P corr=0.015–0.05). Subjects homozygous for the rare alleles of −262 A>T and −115 T>C showed a greater decline in forced expiratory volume in 1 s (FEV1) after aspirin provocation than those homozygous for the common alleles (P<0.05). A luciferase reporter assay indicated that ACE promoters containing the rare −262 A>T allele possessed lower activity than did those containing the common allele (P=0.009). In addition, ACE promoters bearing the rare −115 T>C allele had no luciferase activity. DNA–protein binding assays revealed a band containing the ACE promoter region (including −262 A) and a protein complex.
Conclusion
The −262 A>T polymorphism in the promoter of the ACE gene is associated with AIA, and the rare allele of −262 A>T may confer aspirin hypersensitivity via the down‐regulation of ACE expression.
Background
A virtual reality (VR) tour of the operating theatre before anaesthesia could provide a realistic experience for children. This study was designed to determine whether a preoperative VR ...tour could reduce preoperative anxiety in children.
Methods
Children scheduled for elective surgery under general anaesthesia were randomized into a control or VR group. The control group received conventional information regarding anaesthesia and surgery. The VR group watched a 4‐min video showing Pororo, the famous little penguin, visiting the operating theatre and explaining what is in it. The main outcome was preoperative anxiety, assessed using the modified Yale Preoperative Anxiety Scale (m‐YPAS) before entering the operating theatre. Secondary outcomes included induction compliance checklist (ICC) and procedural behaviour rating scale (PBRS) scores during anaesthesia.
Results
A total of 69 children were included in the analysis, 35 in the control group and 34 in the VR group. Demographic data and induction time were similar in the two groups. Children in the VR group had a significantly lower m‐YPAS score than those in the control group (median 31·7 (i.q.r. 23·3–37·9) and 51·7 (28·3–63·3) respectively; P < 0·001). During anaesthesia, the VR group had lower ICC and PBRS scores than the control group.
Conclusion
This preoperative VR tour of the operating theatre was effective in alleviating preoperative anxiety and increasing compliance during induction of anaesthesia in children undergoing elective surgery. Registration number: UMIN000025232 (http://www.umin.ac.jp/ctr).
Reduces anxiety
The Poisson's ratio is a fundamental mechanical property that relates the resulting lateral strain to applied axial strain. Although this value can theoretically be negative, it is positive for ...nearly all materials, though negative values have been observed in so-called auxetic structures. However, nearly all auxetic materials are bulk materials whose microstructure has been specifically engineered to generate a negative Poisson's ratio. Here we report using first-principles calculations the existence of a negative Poisson's ratio in a single-layer, two-dimensional material, black phosphorus. In contrast to engineered bulk auxetics, this behaviour is intrinsic for single-layer black phosphorus, and originates from its puckered structure, where the pucker can be regarded as a re-entrant structure that is comprised of two coupled orthogonal hinges. As a result of this atomic structure, a negative Poisson's ratio is observed in the out-of-plane direction under uniaxial deformation in the direction parallel to the pucker.
Aims
For the effective production of 146S particles, which determines foot‐and‐mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy‐to‐use, productive and ...economically affordable for the large‐scale production of FMD vaccine.
Methods and Results
Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK‐200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy.
Conclusions
Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale‐up process easy and helps in saving the time and labour involved in spent media removal.
Significance and Impact of the Study
Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial‐scale production of FMD vaccines.
Pressure-driven shock waves in solid materials can cause extreme damage and deformation. Understanding this deformation and the associated defects that are created in the material is crucial in the ...study of a wide range of phenomena, including planetary formation and asteroid impact sites, the formation of interstellar dust clouds, ballistic penetrators, spacecraft shielding and ductility in high-performance ceramics. At the lattice level, the basic mechanisms of plastic deformation are twinning (whereby crystallites with a mirror-image lattice form) and slip (whereby lattice dislocations are generated and move), but determining which of these mechanisms is active during deformation is challenging. Experiments that characterized lattice defects have typically examined the microstructure of samples after deformation, and so are complicated by post-shock annealing and reverberations. In addition, measurements have been limited to relatively modest pressures (less than 100 gigapascals). In situ X-ray diffraction experiments can provide insights into the dynamic behaviour of materials, but have only recently been applied to plasticity during shock compression and have yet to provide detailed insight into competing deformation mechanisms. Here we present X-ray diffraction experiments with femtosecond resolution that capture in situ, lattice-level information on the microstructural processes that drive shock-wave-driven deformation. To demonstrate this method we shock-compress the body-centred-cubic material tantalum-an important material for high-energy-density physics owing to its high shock impedance and high X-ray opacity. Tantalum is also a material for which previous shock compression simulations and experiments have provided conflicting information about the dominant deformation mechanism. Our experiments reveal twinning and related lattice rotation occurring on the timescale of tens of picoseconds. In addition, despite the common association between twinning and strong shocks, we find a transition from twinning to dislocation-slip-dominated plasticity at high pressure (more than 150 gigapascals), a regime that recovery experiments cannot accurately access. The techniques demonstrated here will be useful for studying shock waves and other high-strain-rate phenomena, as well as a broad range of processes induced by plasticity.
Micro (mi)RNAs are small, highly conserved noncoding RNAs that control gene expression post-transcriptionally either via the degradation of target mRNAs or the inhibition of protein translation. Each ...miRNA is believed to regulate the expression of multiple mRNA targets, and many miRNAs have been linked to the initiation and progression of human cancer. miRNAs control various activities of the immune system and different stages of hematopoietic development, and their misexpression is the cause of various blood malignancies. Certain miRNAs have oncogenic activities, whereas others have the potential to act as tumor suppressors. Because they control fundamental processes such as differentiation, cell growth and cell death, the study of the role of miRNAs in human neoplasms holds great promise for novel forms of therapy. Here, we summarize the role of miRNAs and their targets in contributing to human cancers and their function as regulators of apoptotic pathways and the immune system.
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