Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling

Rock walls distribution and Holocene evolution in a mid-latitude mountain range (the Romanian Carpathians)

International audienceRock walls in high mountain areas are the expression of long-term slopes response (10 3-10 5 years) to tectonics, weathering and denudation and a major source of sediment and hazard. Mountain rock walls (RW) characteristics and evolution at mountain-range scale is rarely discussed in the literature. Using a database of 791 RW mapped in the Romanian Carpathians, we present their distribution and morphometry in respect to lithological class, structural features and topography and relate them to post-Younger Dryas (Holocene) rock slope failure chronology. Morphometric data indicate that metamorphic and igneous RW (linked to a great extent to glacial valleys and cirques headwalls) are usually restricted to the highest sectors of the mountain slopes, are characterized by reduced relative heights and have an asymmetrical distribution, being common on the North-exposed slopes but extremely rare on the South. Statistical analysis results show the high significance of structural and tectonic control on RW distribution in sedimentary units which imposes the predominance of West and North orientations and RW dimensions up to a degree higher than in other lithologies. Based on 38 10 Be surface exposure ages obtained on metric boulders from the Southern and Eastern Carpathians, we hypothesise that metamorphic and igneous RW in the formerly glaciated Carpathian valleys were significantly shaped during Early Holocene (before 9 ka) by rock slope failures events that followed the deglaciation of the highest cirques and the intense RW permafrost degradation. We associate the long-term imprints of frost weathering to the significant North/South RW and rock glaciers distribution asymmetry, also identified in other mid-latitude mountain sites with similar topographic constraints

Ethical implications of developing RNA-based therapies for cardiovascular disorders

The awareness concerning RNA-based therapies was boosted significantly after the successful development of COVID-19 vaccines. However, they can potentially lead to significant advances in other areas of medicine, such as oncology or chronic diseases. In recent years, there has been an exponential increase in the number of RNA-based therapies that were evaluated as potential treatments for cardiovascular disorders. One of the areas that was not explicitly assessed about these therapies is represented by their overall ethical framework. Some studies evaluate ethical issues of RNA-based treatments in general or targeting specific disorders (especially neurodegenerative) or interventions for developing RNA-based vaccines. Much less information is available regarding the ethical issues associated with developing these therapeutic strategies for cardiovascular disorders, which is the main aim of this study. We will focus our analysis on three main topics: risk-benefit analysis (including the management of public awareness about these technologies), and justice (in both research and clinical medicine)

Reduced Graphene Oxide Sheets as Inhibitors of the Photochemical Reactions of α-Lipoic Acid in the Presence of Ag and Au Nanoparticles

The influence of Ag and Au nanoparticles and reduced graphene oxide (RGO) sheets on the photodegradation of α-lipoic acid (ALA) was determined by UV-VIS spectroscopy. The ALA photodegradation was explained by considering the affinity of thiol groups for the metallic nanoparticles synthesized in the presence of trisodium citrate. The presence of excipients did not induce further changes when ALA interacts with Ag and Au nanoparticles with sizes of 5 and 10 nm by exposure to UV light. Compared to the Raman spectrum of ALA powder, changes in Raman lines’ position and relative intensities when ALA has interacted with films obtained from Au nanoparticles with sizes between 5 and 50 nm were significant. These changes were explained by considering the chemical mechanism of surface-enhanced Raman scattering (SERS) spectroscopy. The photodegradation of ALA that had interacted with metallic nanoparticles was inhibited in the presence of RGO sheets

Emotional Intolerance and Core Features of Anorexia Nervosa: A Dynamic Interaction during Inpatient Treatment? Results from a Longitudinal Diary Study.

OBJECTIVE:The role of emotion dysregulation with regard to the psychopathology of anorexia nervosa (AN) is increasingly discussed. It is both assumed that AN symptoms have an impact on difficulties in tolerating aversive emotions and that-conversely-emotion dysregulation influences AN. To date, such conclusions are drawn on the basis of cross-sectional data not allowing for inferences on the temporal dynamics. The current study investigates the longitudinal interaction between emotional intolerance and core AN symptoms over the course of inpatient treatment by comparing patients with high (BMI<15 kg/m2) vs. low symptom severity (HSS vs. LSS). METHOD:The study adopted a longitudinal, process-oriented design with N = 16 analysed electronic diaries. Throughout the course of their inpatient treatment, the patients answered questions daily about emotional intolerance and their AN-specific cognitions and behaviours. The temporal dynamics between emotional intolerance and these variables were analysed using a multivariate time series approach. RESULTS:The time series of the processes under investigation adequately reflected the individual treatment courses. The majority of significant linear time trends was found for HSS patients. Most importantly, analysis revealed significant temporal interactions between emotional intolerance and AN symptoms in almost 70% of HSS patients. Thereby, up to 37% of variance in eating restraint and up to 23% in weight concern could be attributed to changes in emotional intolerance. CONCLUSIONS:The findings support the notion that intolerable unpleasant emotions in severely affected AN patients influence their psychopathology. Additionally, time series analysis outlined the inter-individual heterogeneity of psychosomatic treatment courses of AN patients

Glioblastoma and glioblastoma stem-like cancer cells radiosensitization to X-ray and carbon ions using ATM and ATR inhibitors

International audienceGlioblastoma multiform (GBM) represents the deadliest brain cancer, being extremely chemo- and radioresistant. To overcome the resistance to radiotherapy, the use of DNA repair inhibitors was explored for photons and particle irradiation. The treatment with ATM (AZD1390, 10nM) and ATR (VE822, 100nM) DNA repair inhibitors in combination with X-ray and carbon ions was investigated in several commercial human GBM cell lines: U251, U87, U118, T98G and two stem-like cell lines: R633 (p53 mutated) and TG-1 (ATM missense mutation), isolated from neurosurgical biopsy of human GBM. The cells were treated with inhibitors before exposure to X-ray or carbon ion beam (28 and 73KeV/um2). Proliferation index, LDH release and senescence induction were evaluated 5 days post-irradiation. In addition, clonogenic survival was measured inU251 cells. The cell lines range from most radiosensitive to most radioresistant as follows: U87, TG-1, R633, T98G, U251, U118. ATMi induced a higher sensitization than ATRi in all cell lines, as measured by poliferation index after X-ray irradiation. The highest sensitization was induced in U87, U118 and U251 cells and the lowest in the stem-like cells, were ATRi had almost no effect. LDH release is not induced by inhibitors alone, but it is detected following irradiation alone and in combination with inhibitors. Stem-like cells presented more LDH release suggesting higher cellular death. Radiation alone and combination with DNA damage inhibitors induced senescence in the most radiosensitive cell lines (U118, U87) and in both stem-like cells. Clonogenic survival showed lower survival following carbon ions then X-ray, and moreover, a lower survival at higher LET beam. In conclusion, the proposed inhibitors are a promising tool for glioblastoma treatment in combination with radiotherapy. However, individual genetic and epigenetic background likely affects radiosensitivity and treatment response of tumor cell and can modulate the therapeutic outcome

Glioblastoma and glioblastoma stem-like cancer cells radiosensitization to X-ray and carbon ions using ATM and ATR inhibitors

International audienceGlioblastoma multiform (GBM) represents the deadliest brain cancer, being extremely chemo- and radioresistant. To overcome the resistance to radiotherapy, the use of DNA repair inhibitors was explored for photons and particle irradiation. The treatment with ATM (AZD1390, 10nM) and ATR (VE822, 100nM) DNA repair inhibitors in combination with X-ray and carbon ions was investigated in several commercial human GBM cell lines: U251, U87, U118, T98G and two stem-like cell lines: R633 (p53 mutated) and TG-1 (ATM missense mutation), isolated from neurosurgical biopsy of human GBM. The cells were treated with inhibitors before exposure to X-ray or carbon ion beam (28 and 73KeV/um2). Proliferation index, LDH release and senescence induction were evaluated 5 days post-irradiation. In addition, clonogenic survival was measured inU251 cells. The cell lines range from most radiosensitive to most radioresistant as follows: U87, TG-1, R633, T98G, U251, U118. ATMi induced a higher sensitization than ATRi in all cell lines, as measured by poliferation index after X-ray irradiation. The highest sensitization was induced in U87, U118 and U251 cells and the lowest in the stem-like cells, were ATRi had almost no effect. LDH release is not induced by inhibitors alone, but it is detected following irradiation alone and in combination with inhibitors. Stem-like cells presented more LDH release suggesting higher cellular death. Radiation alone and combination with DNA damage inhibitors induced senescence in the most radiosensitive cell lines (U118, U87) and in both stem-like cells. Clonogenic survival showed lower survival following carbon ions then X-ray, and moreover, a lower survival at higher LET beam. In conclusion, the proposed inhibitors are a promising tool for glioblastoma treatment in combination with radiotherapy. However, individual genetic and epigenetic background likely affects radiosensitivity and treatment response of tumor cell and can modulate the therapeutic outcome

Time Course of Leptin in Patients with Anorexia Nervosa during Inpatient Treatment: Longitudinal Relationships to BMI and Psychological Factors

<div><p>Background</p><p>Leptin, a hormone secreted by adipose tissue, appears to play a major role in the homeostasis of body weight and psychobiological processes associated with anorexia nervosa (AN). However, there is scarce data on its exact influence on this disorder, in particular data over time.</p><p>Objective</p><p>The present study addresses whether leptin changes during inpatient treatment play a role for treatment outcome and psychological factors in underweight AN patients.</p><p>Methods</p><p>In order to understand whether leptin’s role differs in relation to AN severity, data were assessed from 11 patients with a very low BMI and a higher chronicity (high severity group; HSS; mean BMI at the beginning of the study = 13.6; mean duration of illness = 5.1 years) vs. nine with less severe symptoms (LSS; mean BMI = 16.2; mean duration of illness = 3.7 years). During the course of treatment, serum leptin concentrations were assessed weekly while weight (BMI) was assessed twice per week. Concomitantly, psychological variables were obtained by means of electronic diaries. Unconditional linear growth models were calculated to evaluate the temporal course of leptin in relation to BMI. For HSS patients, two phases of treatment (BMI < 16 and BMI ≥ 16 kg/m²) were investigated.</p><p>Results</p><p>Leptin increased significantly with BMI in both groups of patients. For HSS patients, the increase of leptin in the first treatment phase did not predict later increases in BMI. Furthermore, the relationship of leptin and psychological factors was modulated by symptom severity. In HSS patients, higher leptin levels were associated with greater feelings of depression, anxiety, and stress whereas in LSS patients a higher leptin level showed the trend to be associated with lower psychological symptom burden.</p><p>Conclusions</p><p>Our results suggest that leptin changes are differently associated with weight gain and psychological symptoms depending on the severity of starvation.</p></div

Significant linear time trends of longitudinal regressions during inpatient treatment

<p>Significant linear time trends of longitudinal regressions during inpatient treatment</p

Average leptin serum concentrations (mean values) plotted against the BMI status of HSS and LSS patients (in increasing order).

<p>HSS = patient group with high symptom severity; LSS = patient group with less severe symptoms. Leptin was measured in μg/ l. Standard deviations (sd) are plotted in grey, number of measurements are plotted as black dots. Note that statistical analyses in the LSS group were performed starting with BMI = 16 kg/m².</p