MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from ...the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.
Aim
To assess the connection between mitophagy and hypoxia‐induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of ...mitophagy‐related apoptosis.
Methodology
Hypoxia‐induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC‐1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN‐induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved‐poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t‐test were used for data analysis.
Results
Hypoxia‐induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia‐augmented apoptotic activity. Simvastatin alleviated hypoxia‐induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts.
Conclusions
The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.
Future weak lensing surveys potentially hold the highest statistical power for constraining cosmological parameters compared to other cosmological probes. The statistical power of a weak lensing ...survey is determined by the sky coverage, the inverse of the noise in shear measurements and the galaxy number density. The combination of the latter two factors is often expressed in terms of n
eff - the 'effective number density of galaxies used for weak lensing measurements'. In this work, we estimate n
eff for the Large Synoptic Survey Telescope (LSST) project, the most powerful ground-based lensing survey planned for the next two decades. We investigate how the following factors affect the resulting n
eff of the survey with detailed simulations: (1) survey time, (2) shear measurement algorithm, (3) algorithm for combining multiple exposures, (4) inclusion of data from multiple filter bands, (5) redshift distribution of the galaxies and (6) masking and blending. For the first time, we quantify in a general weak lensing analysis pipeline the sensitivity of n
eff to the above factors.
We find that with current weak lensing algorithms, expected distributions of observing parameters, and all lensing data (r and i band, covering 18 000 degree2 of sky) for LSST, n
eff 37 arcmin−2 before considering blending and masking, n
eff 31 arcmin−2 when rejecting seriously blended galaxies and n
eff 26 arcmin−2 when considering an additional 15 per cent loss of galaxies due to masking. With future improvements in weak lensing algorithms, these values could be expected to increase by up to 20 per cent. Throughout the paper, we also stress the ways in which n
eff depends on our ability to understand and control systematic effects in the measurements.
Summary
Background
Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult‐onset asthma ...in community‐based populations.
Objective
We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community‐based adult populations.
Methods
The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin‐specific IgE using ImmunoCAP.
Results
Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin‐specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin‐specific IgE level was identified as the major determinant factor for total IgE level.
Conclusions and Clinical Relevance
Staphylococcal enterotoxin sensitization was independently associated with adult‐onset asthma in adult community populations. Strong correlations between the enterotoxin‐specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.
Laser-plasma accelerators of only a centimetre's length have produced nearly monoenergetic electron bunches with energy as high as 1 GeV. Scaling these compact accelerators to multi-gigaelectronvolt ...energy would open the prospect of building X-ray free-electron lasers and linear colliders hundreds of times smaller than conventional facilities, but the 1 GeV barrier has so far proven insurmountable. Here, by applying new petawatt laser technology, we produce electron bunches with a spectrum prominently peaked at 2 GeV with only a few per cent energy spread and unprecedented sub-milliradian divergence. Petawatt pulses inject ambient plasma electrons into the laser-driven accelerator at much lower density than was previously possible, thereby overcoming the principal physical barriers to multi-gigaelectronvolt acceleration: dephasing between laser-driven wake and accelerating electrons and laser pulse erosion. Simulations indicate that with improvements in the laser-pulse focus quality, acceleration to nearly 10 GeV should be possible with the available pulse energy.
Objectives
High salt intake results in various harmful effects on human health including hypertension, cardiovascular disease, and reduced bone density. Despite this, there are very few studies in ...the literature that have investigated the association between sodium intake and osteoarthritis (OA). Therefore, we aimed to explore these associations in a Korean population.
Methods
This study used cross-sectional data from adult subjects aged 50–75 years from two consecutive periods of the Korean National Health and Nutrition Examination Survey V–VII (2010–2011 and 2014–2016). The estimated 24-hour urinary sodium excretion (24HUNa) was used as a surrogate marker of salt intake. In the 2010–2011 dataset, knee OA (KOA) was defined as the presence of the radiographic features of OA and knee pain. The association between KOA and salt intake was analysed using univariable and multivariable logistic regression methods. For the sensitivity analysis, the same procedures were conducted on subjects with self-reported OA (SR-OA) with knee pain in the 2010–2011 dataset and any site SR-OA in the 2014–2016 dataset.
Results
Subjects with KOA had significantly lower energy intake, but higher 24HUNa than those without KOA. The restricted cubic spline plots demonstrated a J-shaped distribution between 24HUNa and prevalent KOA. When 24HUNa was stratified into five groups (<2, 2–3, 3–4, 4–5 and ≥5 g/day), subjects with high sodium intake (≥5 g/day) had a higher risk of KOA (odds ratio OR = 1.64, 95% confidence interval CI 1.03–2.62) compared to the reference group (3–4 g/day) after adjusting for covariates. The sensitivity analysis based on SR-OA with knee pain showed that high sodium intake was also significantly associated with increased prevalence of OA (OR = 1.84, 95% CI 1.10–3.10) compared with the reference group. Regarding SR-OA at any site in the 2014–2016 dataset, estimated 24HUNa showed a significantly positive association with the presence of SR-OA after adjusting for potential confounders.
Conclusions
This nationwide Korean representative study showed a significant association between symptomatic KOA and high sodium intake (≥5 g/day). Avoidance of a diet high in salt might be beneficial as a non-pharmacologic therapy for OA.
The concept of severity in irritable bowel syndrome (IBS) is clinically recognized and operative in diagnostic decision making and treatment planning. Yet, there is no consensus on its definition, ...and there are limited data on the prevalence of severity subgroups, its medical and psychosocial determinants, and its association with other health status measures. The aims of the Rome Foundation Working Team Committee were to summarize current research, to develop a consensus of understanding on this concept, and to make recommendations for its use in research and clinical care.
In 2006, a multinational committee of clinical investigators with expertise in IBS and/or psychometric research methods undertook a systematic review of the literature relating to severity in IBS. Owing to limited data, the Foundation commissioned three clinical studies to better characterize the concept of severity in IBS, and summary information and recommendations for future research and clinical care were developed.
The main findings were: (i) severity in IBS is defined as a biopsychosocial composite of patient-reported gastrointestinal and extraintestinal symptoms, degree of disability, and illness-related perceptions and behaviors; (ii) both visceral and central nervous system physiological factors affect severity; as severity increases, the central nervous system provides a greater contribution; (iii) severity is related to and influences health-related quality of life and health behaviors and also guides diagnostic and therapeutic clinical decision making; (iv) severity can be subcategorized into clinically meaningful subgroups as mild (∼40%), moderate (∼35%), and severe (∼25%), and this provides a working model for use in future research and clinical care.
Future work is required to understand more precisely the factors contributing to severity and to develop a valid patient-reported instrument to measure severity in IBS.
Cognitive impairment is a core feature of schizophrenia. Its relationship with duration of untreated psychosis (DUP), a potentially malleable prognostic factor, has been less studied, with ...inconsistent findings being observed in the literature. Previous research investigating such a relationship was mostly cross-sectional and none of those prospective studies had a follow-up duration beyond 2 years. Method A total of 93 Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. DUP and pre-morbid adjustment were measured using a structured interview incorporating multiple sources of information. Psychopathological evaluation was administered at intake, after clinical stabilization of the first psychotic episode, and at 12, 24 and 36 months. Cognitive functions were measured at clinical stabilization, and at 12, 24 and 36 months.
DUP exerted differential effects on various cognitive domains, with memory deficits being the most related to DUP even when potential confounders including pre-morbid adjustment and sex were adjusted. Prolonged DUP was associated with more severe impairment in visual memory at clinical stabilization and verbal memory at 24 and 36 months. Further, patients with a long DUP were found to have worse outcomes on negative symptoms at 36 months. The effects of DUP on verbal memory remained significant even when negative symptoms were taken into consideration.
Our findings provided further supportive evidence that delayed treatment to first-episode psychosis is associated with poorer cognitive and clinical outcomes. In addition, DUP may specifically affect memory function and its adverse impact on verbal memory may only become evident at a later stage of the recovery process.
PDF
