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An<em> </em>inhibitory function of TRPA1 channels in TGF-β1-driven fibroblast to myofibroblast differentiation.
No full textTransient receptor potential ankyrin 1 (TRPA1) is a non-selective Ca2+ permeable cation channel, which was originally cloned from human lung fibroblasts (HLFs). TRPA1-mediated Ca2+ entry is evoked by exposure to several chemicals, including allyl isothiocyanate (AITC), and a protective effect of TRPA1 activation in the development of cardiac fibrosis has been proposed. Yet, the function of TRPA1 in transforming growth factor β1 (TGF-β1)-driven fibroblast to myofibroblast differentiation and the development of pulmonary fibrosis remains elusive. TRPA1 expression and function was analyzed in cultured primary HLFs, and mRNA levels were significantly reduced after adding TGF-β1. Expression of genes encoding fibrosis markers, e.g. alpha smooth muscle actin (ACTA2), plasminogen activator inhibitor 1 (SERPINE1), fibronectin (FN1) and type I collagen (COL1A1) was increased after siRNA-mediated down-regulation of TRPA1-mRNA in HLFs. Moreover, AITC-induced Ca2+ entry in HLFs was decreased after TGF-β1 treatment and by application of TRPA1 siRNAs, while AITC treatment alone did not reduce cell viability or enhanced apoptosis. Most interestingly, AITC-induced TRPA1 activation augmented ERK1/2 phosphorylation, which might inhibit TGF-β-receptor signaling. Our results suggest an inhibitory function of TRPA1 channels in TGF-β1-driven fibroblast to myofibroblast differentiation. Therefore, activation of TRPA1 channels might be protective during the development of pulmonary fibrosis in patients
Insights into the molecular landscape of osteoarthritis in human tissues.
No full textPURPOSE OF REVIEW: To provide an overview of recent developments in the field of osteoarthritis research with a focus on insights gleaned from the application of different -omic technologies. RECENT FINDINGS: We searched for osteoarthritis-relevant studies focusing on transcriptomics, epigenomics, proteomics and metabolomics, published since November of 2019. Study designs showed a trend towards characterizing the genomic profile of osteoarthritis-relevant tissues with high resolution, for example either by using single-cell technologies or by considering several -omic levels and disease stages. SUMMARY: Multitissue interactions (cartilage-subchondral bone; cartilage-synovium) are prevalent in the pathophysiology of osteoarthritis, which is characterized by substantial matrix remodelling in an inflammatory milieu. Subtyping approaches using -omic technologies have contributed to the identification of at least two osteoarthritis endotypes. Studies using data integration approaches have provided molecular maps that are tissue-specific for osteoarthritis and pave the way for expanding these data integration approaches towards a more comprehensive view of disease aetiopathogenesis
The skin microbiome as a clinical biomarker in atopic eczema: Promises, navigation, and pitfalls.
No full textAssociation of green space with bone mineral density change and incident fracture in elderly Hong Kong Chinese: Mr. OS and Ms. OS study.
No full textBackground: A large body of literature has reported positive effects of green space (GS) on various aspects of health and well-being, while no studies explore the role of GS in bone health. Objectives: The present study aimed to investigate the associations of GS with bone mineral density (BMD) change and incident fracture in a prospective cohort of elderly Hong Kong Chinese. Methods: Between 2001 and 2003, 3944 participants aged 65 years and older at baseline were recruited. GS (%) within 300-m and 500-m buffers were calculated for each participant based on the Normalized Difference Vegetation Index. BMD at whole body, lumbar spine, total hip, and femoral neck were assessed by dual energy X-ray absorptiometry at baseline and 3 follow-ups. Incident fracture cases were ascertained from the electronic database of Hospital Authority of Hong Kong. Linear mixed-effects models and Cox proportional hazards models were used to investigate the associations of GS with changes in BMD and incident fracture, respectively. Results: Greater GS within 300-m and 500-m buffers were associated with a slower increase in lumbar spine BMD over 14 years. After adjustment for potential confounders, β and 95% confidence intervals (CIs) of change in BMD across Q2-Q4 (quartiles of GS measured in a 300-m, compared with Q1) were −6.42 (−12.3, −0.59), −7.78 (−13.6, −1.97), and −7.83 (−13.7, −2.00) mg/cm3, respectively. GS was also positively associated with non-spinal fracture and major osteoporotic fracture incidence risks. Multivariable-adjusted hazard ratios (95%CIs) were 1.40 (1.09, 1.79; P-trend = 0.036) for non-spinal fracture and 1.53 (1.13, 2.07; P-trend = 0.010) for major osteoporotic fracture (Q4 compared with Q1 of GS measured in a 300-m buffer). Positive GS-fracture associations were also found for GS within a 500-m buffer. Conclusions: We found that those who lived near higher GS levels had a slower increase in lumbar spine BMD and had higher incident fracture risk
Stem cell-derived β cells go in monkeys.
No full textDu et al. transplanted β cells derived from pluripotent stem cells in diabetic monkeys for the first time, as an intermediate stage toward clinical translation. They observed benefits unfolding over months but also observed immune rejection of the grafts by 5–6 months
Circulating metabolites associate with and improve the prediction of all-cause mortality in type 2 diabetes.
No full textDeath rate is increased in type 2 diabetes. Unraveling biomarkers of novel pathogenic pathways capable to identify high-risk patients is instrumental to tackle this burden. We investigated the association between serum metabolites and all-cause mortality in type 2 diabetes and then, whether the associated metabolites mediate the effect of inflammation on mortality risk and improve ENFORCE and RECODe, two well-established all-cause mortality prediction models in diabetes. Two cohorts comprising 856 individuals (279 all-cause deaths) were analyzed. Serum metabolites (n=188) and pro- and anti-inflammatory cytokines (n=7) were measured. In the pooled analysis, hexanoylcarnitine, kynurenine and tryptophan were significantly and independently associated with mortality (HRs, [95%CIs] 1.60, [1.43-1.80]; 1.53, [1.37-1.71]; 0.71, [0.62-0.80] per 1SD). The kynurenine/tryptophan ratio (KTR-a proxy of indoleamine-2,3-dioxygenase which degrades tryptophan to kynurenine and contribute to a pro-inflammatory status) mediated 42% of the significant association between the anti-atherogenic IL-13 and mortality. Adding the three metabolites improved discrimination and reclassification (all P<0.01) of both mortality prediction models. In type 2 diabetes, hexanoylcarnitine, tryptophan and kynurenine are associated to and improve the prediction of all-cause mortality. Further studies are needed to investigate whether interventions aimed at reducing KTR, also reduce the risk of death especially in patients with low IL-13
Heterogeneous development of β-cell populations In diabetes-resistant and -susceptible mice.
No full textProgressive dysfunction and failure of insulin-releasing β-cells is a hallmark of type 2 diabetes (T2D). To study mechanisms of β-cell loss in T2D, we performed islet single-cell RNA-sequencing of two obese mouse strains differing in their diabetes susceptibility. On a control diet, we identified six β-cell clusters with similar abundance in both strains. However, after feeding a diabetogenic diet for two days, β-cell cluster composition markedly differed between strains. Islets of diabetes-resistant mice developed into a protective β-cell cluster (Beta4), whereas those of diabetes-prone mice progressed towards stress-related clusters with a strikingly different expression pattern. Interestingly, the protective cluster showed indications of reduced β-cell identity, such as downregulation of GLUT2, GLP1R and MafA, and in-vitro knockdown of GLUT2 in β-cells to mimick its phenotype decreased stress response and apoptosis. This might explain enhanced β-cell survival of diabetes-resistant islets. In contrast, β-cells of diabetes-prone mice responded with expression changes indicating metabolic pressure and ER stress, presumably leading to later β-cell loss. In conclusion, failure of diabetes-prone mice to adapt gene expression towards a more dedifferentiated state in response to rising blood glucose levels leads to β-cell failure and diabetes development
Chronobiology: Is daylight saving time a deer saving time?
No full textEarlier human activity relative to sunrise and sunset, the very essence of daylight saving time, is linked with health and safety detriments in humans. A new study predicts that deer, at least, may benefit from earlier human activity through reduced deer-vehicle collisions
Lower hepatic fat is associated with improved insulin secretion in a high-risk prediabetes subphenotype during lifestyle intervention.
No full textThe objective of this work was to investigate whether impaired insulin secretion can be restored by lifestyle intervention in specific subphenotypes of prediabetes. One thousand forty-five participants from the Prediabetes Lifestyle Intervention Study (PLIS) were assigned to 6 recently established prediabetes clusters. Insulin secretion was assessed by a C-peptide-based index derived from oral glucose tolerance tests and modeled from three time-points during a 1-yr intervention. We also analyzed the change of glycemia, insulin sensitivity and liver fat. All pre-diabetes high-risk clusters (cluster 3, 5 and 6) had improved glycemic traits during lifestyle intervention, whereas insulin secretion only increased in clusters 3 and 5 (p<0.001); however, high liver fat in cluster 5 was associated with a failure to improve insulin secretion (pinteraction<0.001). Thus, interventions to reduce liver fat have the potential to improve insulin secretion in a defined subgroup of prediabetes. Prediabetes is a heterogenous condition comprising subphenotypes with different risks of diabetes and its complications (1). From its two key features, insulin resistance and impaired insulin secretion, insulin resistance can be clearly improved by lifestyle intervention (LI); however, it is not known, if LI can improve insulin secretion in specific subphenotypes of reduced insulin secretion (2). Recently, we described 6 clusters of prediabetic metabolism (1). Two of these clusters (cluster 3 and 5) have high risk of progression to diabetes. Another group (cluster 6) has an intermediate risk of diabetes as these persons are capable of compensating insulin resistance via hyperinsulinemia over years. In this study, we retrospectively stratified participants of a large multi-center study into these novel clusters of prediabetic metabolism (1) and investigated whether LI improved their insulin secretion and other glycemic traits
Perceptions of change in the environment caused by the COVID-19 pandemic: Implications for environmental policy.
No full textCOVID-19 lockdown measures have impacted the environment with both positive and negative effects. However, how human populations have perceived such changes in the natural environment and how they may have changed their daily habits have not been yet thoroughly evaluated. The objectives of this work were to investigate (1) the social perception of the environmental changes produced by the COVID-19 pandemic lockdown and the derived change in habits in relation to i) waste management, energy saving, and sustainable consumption, ii) mobility, iii) social inequalities, iv) generation of noise, v) utilization of natural spaces, and, vi) human population perception towards the future, and (2) the associations of these potential new habits with various socio-demographic variables. First, a SWOT analysis identified strengths (S), weaknesses (W), opportunities (O), and threats (T) generated by the pandemic lockdown measures. Second, a survey based on the aspects of the SWOT was administered among 2370 adults from 37 countries during the period from February to September 2021. We found that the short-term positive impacts on the natural environment were generally well recognized. In contrast, longer-term negative effects arise, but they were often not reported by the survey participants, such as greater production of plastic waste derived from health safety measures, and the increase in e-commerce use, which can displace small storefront businesses. We were able to capture a mismatch between perceptions and the reported data related to visits to natural areas, and generation of waste. We found that age and country of residence were major contributors in shaping the survey participants ´answers, which highlights the importance of government management strategies to address current and future environmental problems. Enhanced positive perceptions of the environment and ecosystems, combined with the understanding that livelihood sustainability, needs to be prioritized and would reinforce environmental protection policies to create greener cities. Moreover, new sustainable jobs in combination with more sustainable human habits represent an opportunity to reinforce environmental policy