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Translational Research : the Journal of... Jun 2024Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the...
Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the abnormal expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of RNA N6-methyladenosine, is critically involved in cisplatin-induced renal tubular senescence. In cisplatin-induced senescence of RTECs, the promoter activity and transcription of IGF2BP3 is markedly suppressed. It was due to the down regulation of MYC proto-oncogene (MYC), which regulates IGF2BP3 transcription by binding to the putative site at 1852 to 1863 of the IGF2BP3 promoter. Overexpression of IGF2BP3 ameliorated cisplatin-induced renal tubular senescence in vitro. Mechanistic studies revealed that IGF2BP3 inhibits cellular senescence in RTECs by enhancing cyclin-dependent kinase 6 (CDK6) mRNA stability and increasing its expression. The inhibition effect of IGF2BP3 on tubular senescence is partially reversed by the knockdown of CDK6. Further, IGF2BP3 recruits nuclear cap binding protein subunit 1 (NCBP1) and inhibits CDK6 mRNA decay, by recognizing mA modification. Specifically, IGF2BP3 recognizes mA motif "GGACU" at nucleotides 110-114 in the 5' untranslated region (UTR) field of CDK6 mRNA. The involvement of IGF2BP3/CDK6 in alleviating tubular senescence was confirmed in a cisplatin-induced acute kidney injury (AKI)-to-chronic kidney disease (CKD) model. Clinical data also suggests an age-related decrease in IGF2BP3 and CDK6 levels in renal tissue or serum samples from patients. These findings suggest that IGF2BP3/CDK6 may be a promising target in cisplatin-induced tubular senescence and renal failure.
PubMed: 38945255
DOI: 10.1016/j.trsl.2024.06.004 -
The Lancet. Healthy Longevity Jul 2024Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated...
BACKGROUND
Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated with an increased risk of developing such hallmark-related diseases.
METHODS
In this multicohort study, we included people aged 38-72 years with data on weight, height, and waist circumference measured during a clinical examination at baseline between March 13, 2006, and Oct 1, 2010, from the UK Biobank with follow-up until Nov 12, 2021. To test reproducibility of the findings (replication analysis), we used data from people aged 40 years or older included in the Finnish Public Sector study and the Finnish Health and Social Support study who responded to the study surveys, had data on BMI, and were successfully linked to electronic health records from national registers up to Dec 31, 2016. Obesity and clinical characteristics were assessed at baseline. Via linkage to national health records, participants were followed up for 83 diseases related to nine ageing hallmarks (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication). Outcomes were the first instance of hallmark-related disease, in addition to co-occurrence of three or more hallmark-related diseases and mortality.
FINDINGS
496 530 adults (mean age 57·0 years [SD 8·1]) from the UK Biobank were included in the primary analysis, and 83 249 (mean age 48·2 years [6·4]) adults from the Finnish cohorts were included in the replication analysis. Median follow-up was 12·7 years (IQR 12·0-13·4) in the UK Biobank and 14·0 years (8·0-15·0) in the Finnish cohorts. After adjusting for demographic characteristics, lifestyle factors, and depression, UK Biobank participants with obesity (BMI ≥30·0 kg/m) had a 1·40 (95% CI 1·38-1·41) times higher hazard ratio for the first hallmark-related disease than those with a healthy weight (BMI 18·5-24·9 kg/m). The corresponding hazard ratios for three co-occurring diseases were 2·92 (95% CI 2·64-3·22) for deregulated nutrient sensing, 2·73 (2·46-3·02) for telomere attrition, 2·33 (2·10-2·60) for epigenetic alterations, 2·30 (2·14-2·48) for mitochondrial dysfunction, 2·23 (2·04-2·45) for stem cell exhaustion, 2·02 (1·89-2·16) for altered intercellular communication, 2·01 (1·89-2·15) for cellular senescence, 1·83 (1·67-2·00) for loss of proteostasis, and 1·39 (1·27-1·52) for genomic instability. These findings were replicated in the Finnish cohorts. In both studies, the associations between other risk factors (low education, unhealthy dietary factors [available only in the UK Biobank], smoking, high alcohol consumption, physical inactivity, and depression) and hallmark-related diseases were weaker than those with obesity. 45-60% of the excess mortality in people with obesity was attributable to hallmark-related diseases.
INTERPRETATION
Obesity might have an important role in the development of diseases associated with cellular ageing. Tackling ageing mechanisms could potentially help to reduce the disease and mortality burden resulting from the obesity epidemic.
FUNDING
Wellcome Trust, UK Medical Research Council, US National Institute on Aging, Academy of Finland, and Finnish Foundation for Cardiovascular Research.
TRANSLATIONS
For the German and Finnish translations of the abstract see Supplementary Materials section.
Topics: Humans; Obesity; Middle Aged; Male; Female; Aged; Adult; Cellular Senescence; Finland; Cohort Studies; Risk Factors; Aging; United Kingdom; Body Mass Index
PubMed: 38945128
DOI: 10.1016/S2666-7568(24)00087-4 -
Australian and New Zealand Journal of... Jun 2024We sought to explore the lived experience of people with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) to inform the development of a potential treatment...
OBJECTIVE
We sought to explore the lived experience of people with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) to inform the development of a potential treatment intervention.
METHODS
We conducted one-to-one in-depth, semi-structured interviews with 13 people living in Australia affected by DSCATT. Interviews were transcribed and analysed using thematic analysis.
RESULTS
Although participants attributed the origin of their illness to tick bites, not all were adamant they had Lyme disease. Negative experiences in conventional healthcare were marked and were reported to exacerbate the impact of the illness and affect mental health. Further, these negative experiences propelled participants to seek unapproved treatments (by Australian standards). The desire for the illness to be acknowledged and causative agents identified was pronounced among the participant group.
CONCLUSIONS
Individuals with DSCATT experience significant challenges amid a contentious healthcare landscape surrounding chronic symptoms attributed to ticks in Australia. Our findings suggest the need for empathetic, supportive and patient-centred treatments for this cohort.
IMPLICATIONS FOR PUBLIC HEALTH
DSCATT results in a considerable burden across multiple domains for those affected. Negative experiences with healthcare exacerbate the suffering of people with DSCATT in Australia. New approaches that acknowledge the illness experience of people with DSCATT, alongside evidence-based treatments that encompass biopsychosocial models of care, are needed to tackle this debilitating condition.
PubMed: 38945055
DOI: 10.1016/j.anzjph.2024.100163 -
Journal of Hazardous Materials Jun 2024In response to the need for trace arsenic removal and detoxification, an electro-assisted self-alkalization and oxidant-free processes (ESOP) cell was developed and...
In response to the need for trace arsenic removal and detoxification, an electro-assisted self-alkalization and oxidant-free processes (ESOP) cell was developed and investigated. It was found that the ESOP removed 90.3 % of arsenic and reduced the As(III) concentration from 150 µg L to less than 5 µg L in its cathode chamber. The As removal involved migration of As(III) and As(V) from the cathode to the anode driven by electrical current. In the ESOP cathode, As(III) was dissociated to As(III) oxyanions via alkalization and then oxidized into As(V) by HO. Nearly 80 % of As(III) migration could be attributed to the oxidation by HO and approximately 20 % dissociation by pH alkalization. The voltage-controlled conditions (1.2 -1.5 V) achieved a peak cumulative HO concentration of 10.9 mg L. The ESOP demonstrated a high As(III) oxidation to As(V) conversion efficiency of 97.0 % as well as a low energy cost of 0.013 kWh m at 1.2 V. The migrated arsenic was stabilized onto the anode electrode through in-situ electro-oxidation of As(III) and electrosorption of As(III, V); this would help with the post-treatment waste disposal. Those results have provided important insights into an electrochemical approach for highly efficient arsenic detoxification.
PubMed: 38944991
DOI: 10.1016/j.jhazmat.2024.135025 -
Cytotherapy Jun 2024Natural killer (NK) cells make only a small fraction of immune cells in the human body, however, play a pivotal role in the fight against cancer by the immune system.... (Review)
Review
Natural killer (NK) cells make only a small fraction of immune cells in the human body, however, play a pivotal role in the fight against cancer by the immune system. They are capable of eliminating abnormal cells via several direct or indirect cytotoxicity pathways in a self-regulating manner, which makes them a favorable choice as a cellular therapy against cancer. Additionally, allogeneic NK cells, unlike other lymphocytes, do not or only minimally cause graft-versus-host diseases opening the door for an off-the-shelf therapy. However, to date, the production of NK cells faces several difficulties, especially because the critical process parameters (CPPs) influencing the critical quality attributes (CQAs) are difficult to identify or correlate. There are numerous different cultivation platforms available, all with own characteristics, benefits and disadvantages that add further difficulty to define CPPs and relate them to CQAs. Our goal in this contribution was to summarize the current knowledge about NK cell expansion CPPs and CQAs, therefore we analyzed the available literature of both dynamic and static culture format experiments in a systematic manner. We present a list of the identified CQAs and CPPs and discuss the role of each CPP in the regulation of the CQAs. Furthermore, we could identify potential relationships between certain CPPs and CQAs. The findings based on this systematic literature research can be the foundation for meaningful experiments leading to better process understanding and eventually control.
PubMed: 38944794
DOI: 10.1016/j.jcyt.2024.05.025 -
The Science of the Total Environment Jun 2024Shipping activity can be a substantial source of pollution and impact on the environment, including air, water and ecosystems, as well as adverse health and climatic...
Shipping activity can be a substantial source of pollution and impact on the environment, including air, water and ecosystems, as well as adverse health and climatic effects. Due to the distribution of maritime transport activity routes in the EU, a large portion of the population is exposed to shipping pollution throughout Europe. The ongoing European project EMERGE aims to investigate and quantify these impacts over Europe, and in more detail, in specific case studies regions. The Aveiro lagoon region in Portugal is one of these case studies. This region is a Natura 2000 area, and also includes a medium-sized port. Both air quality and water modelling tools were applied to assess the impact of the emissions and discharges from shipping (to air and water) in the region in 2018. Additionally, ecotoxicological impacts were determined by bioassays to evaluate the impact of scrubber-water discharges on the most sensitive stages of marine invertebrates, and on the post-exposure feeding inhibition of crustacean and bivalve species. The results show that there was a substantial increase in atmospheric pollutant concentrations due to emissions attributed to shipping, which was most relevant for NOx and SO (up to a 30 % shipping contribution). There was no significant degradation of the water quality, mainly as the ships operating in this area did not have scrubber equipment. The ecotoxicological tests were performed with three samples of scrubber water, including one artificial sample and two samples collected on-board ships. If scrubber water would have been discharged in this area, the results indicated that the majority of the tested species would be exposed to lowest observed effect concentration (LOEC) for the different scrubber-water samples, as well as to substantial concentrations of metals, PAHs, and alkylated PAHs.
PubMed: 38944305
DOI: 10.1016/j.scitotenv.2024.174314 -
Environmental Research Jun 2024The Mediterranean Basin has experienced substantial land use changes as traditional agriculture decreased and population migrated from rural to urban areas, which have...
The Mediterranean Basin has experienced substantial land use changes as traditional agriculture decreased and population migrated from rural to urban areas, which have resulted in a large forest cover increase. The combination of Landsat time series, providing spectral information, with lidar, offering three-dimensional insights, has emerged as a viable option for the large-scale cartography of forest structural attributes across long time spans. Here we develop and test a comprehensive framework to map forest above ground biomass, canopy cover and forest height in two regions spanning the most representative biomes in the peninsular Spain, Mediterranean (Madrid region) and temperate (Basque Country). As reference, we used lidar-based direct estimates of stand height and forest canopy cover. The reference biomass and volume were predicted from lidar metrics. Landsat time series predictors included annual temporal profiles of band reflectance and vegetation indices for the 1985-2023 period. Additional predictor variables including synthetic aperture radar, disturbance history, topography and forest type were also evaluated to optimize forest structural attributes retrieval. The estimates were independently validated at two temporal scales, i) the year of model calibration and ii) the year of the second lidar survey. The final models used as predictor variables only Landsat based metrics and topographic information, as the available SAR time-series were relatively short (1991-2011) and disturbance information did not decrease the estimation error. Model accuracies were higher in the Mediterranean forests when compared to the temperate forests (R = 0.6-0.8 vs. 0.4-0.5). Between the first (1985-1989) and the last (2020-2023) decades of the monitoring period the average forest cover increased from 21 ± 2% to 32 ± 1%, mean height increased from 6.6 ± 0.43 m to 7.9 ± 0.18 m and the mean biomass from 31.9 ± 3.6 t ha to 50.4 ± 1 t ha for the Mediterranean forests. In temperate forests, the average canopy cover increased from 55 ± 4% to 59 ± 3%, mean height increased from 15.8 ± 0.77 m to 17.3 ± 0.21m, while the growing stock volume increased from 137.8 ± 8.2 to 151.5 ± 3.8 m ha. Our results suggest that multispectral data can be successfully linked with lidar to provide continuous information on forest height, cover, and biomass trends.
PubMed: 38944104
DOI: 10.1016/j.envres.2024.119432 -
Appetite Jun 2024People often fail to acknowledge external influences on their food intake, but there might be some circumstances in which people are willing to report that those...
People often fail to acknowledge external influences on their food intake, but there might be some circumstances in which people are willing to report that those external factors influenced their behavior. This study examined whether participants who believed that they had overeaten would indicate that the portion size they were served influenced their food intake. Participants (119 women) ate a pasta lunch at two separate sessions, one week apart. At the second session, participants were randomly assigned to receive either a regular portion of pasta (the same portion as the first session) or a large portion of pasta (a portion that was twice the size), and to receive false feedback about their food intake indicating that they had either eaten about the same as or substantially more than they had at the previous session. Participants were then asked to indicate the extent to which the amount of food served influenced how much they ate at that second session. Compared to participants who were informed that they had eaten the same amount across the two sessions, those who were informed that they ate more at the second session reported a stronger influence of the amount of food served if they also received a large portion of pasta, but not if they received a regular portion of pasta. These findings suggest that the willingness to implicate external influences (e.g., portion size) on one's food intake may be driven by a self-serving bias, providing an "excuse" for overeating. However, the external cue must be salient enough to be a plausible explanation for one's behavior.
PubMed: 38944056
DOI: 10.1016/j.appet.2024.107583 -
Design and optimization of THz coupling in zirconia MAS rotors for dynamic nuclear polarization NMR.Journal of Magnetic Resonance (San... Jun 2024We present 3D electromagnetic simulations of the coupling of a 250 GHz beam to the sample in a 380 MHz DNP NMR spectrometer. To obtain accurate results for magic angle...
We present 3D electromagnetic simulations of the coupling of a 250 GHz beam to the sample in a 380 MHz DNP NMR spectrometer. To obtain accurate results for magic angle spinning (MAS) geometries, we first measured the complex dielectric constants of zirconia, sapphire, and the sample matrix material (DNP juice) from room temperature down to cryogenic temperatures and from 220 to 325 GHz with a VNA and up to 1 THz with a THz TDS system. Simulations of the coupling to the sample were carried out with the ANSYS HFSS code as a function of the rotor wall material (zirconia or sapphire), the rotor wall thickness, and the THz beam focusing (lens or no lens). For a zirconia rotor, the B field in the sample was found to be strongly dependent on the rotor wall thickness, which is attributed to the high refractive index of zirconia. The optimum thickness of the wall is likely due to a transmission maximum but is offset from the thickness predicted by a simple calculation for a flat slab of the wall material. The B value was found to be larger for a sapphire rotor than for a zirconia rotor for all cases studied. The results found in this work provide new insights into the coupling of THz radiation to the sample and should lead to improved designs of future DNP NMR instrumentation.
PubMed: 38943993
DOI: 10.1016/j.jmr.2024.107722 -
Food Chemistry Jun 2024False flax (Camelina sativa L.), known as camelina, is an ancient oil plant that has gathered renewed interest. In this study, a comprehensive analysis encompassing...
Unravelling the importance of seed roasting for oil quality by the non-targeted volatilomics and targeted metabolomics of cold-pressed false flax (Camelina sativa L.) oil and press cakes.
False flax (Camelina sativa L.), known as camelina, is an ancient oil plant that has gathered renewed interest. In this study, a comprehensive analysis encompassing nontargeted volatilomics and targeted, quantitative metabolomics performed for cold-pressed oil and press cake and was integrated with sensory analysis of cold-pressed camelina oil and the effect of seed roasting was evaluated. Roasting in general resulted in the formation of 22 new volatile organic compounds (VOCs) in oil, while roasting at 140 and 180 °C resulted in the formation of 12 and 124 unique VOCs, respectively. Roasting notably influenced the profile of primary and secondary metabolites in both oil and press cakes, as well as volatilome and aroma of cold-pressed camelina oil. Many VOCs can be attributed to thermal degradation of primary and secondary metabolites. Roasting intensified the flavour of cold-pressed camelina oil, enhancing the perception of notes formed through the Maillard reaction.
PubMed: 38943959
DOI: 10.1016/j.foodchem.2024.140207