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Therefore, .NO-mediated lysosomal impairment is central in PAL-induced ferroptosis.Macrophages are innate immune cells that internalize and present exogenous antigens to T cells via MHC class II proteins. They operate at sites of infection in a highly inflammatory environment, generated in part by reactive oxygen species, in particular the strong oxidant hypochlorous acid (HOCl) produced in the neutrophil respiratory burst. HOCl effectively kills a broad range of pathogens but can also contribute to host tissue damage at sites of inflammation. To prevent tissue injury, HOCl is scavenged by human serum albumin (HSA) and other plasma proteins in interstitial fluids, leading to the formation of variously modified advanced oxidation products (AOPPs) with pro-inflammatory properties. Previously, we showed that HOCl-mediated N-chlorination converts HSA and other plasma proteins into efficient activators of the phagocyte respiratory burst, but the role of these AOPPs in antigen presentation by macrophages remained unclear. Here, we show that physiologically relevant amounts of N-chlorinated HSA can strongly impair the capacity of THP-1-derived macrophages to present antigens to antigen-specific T cells via MHC class II proteins at multiple stages. Initially, N-chlorinated HSA inhibits antigen internalization by converting antigens into scavenger receptor (SR) ligands and competing with the modified antigens for binding to SR CD36. Later steps of antigen presentation, such as intracellular antigen processing and MHC class II expression are negatively affected, as well. We propose that impaired processing of pathogens or exogenous antigens by immune cells at an initial stage of infection prevents antigen presentation in an environment potentially hostile to cells of the adaptive immune response, possibly shifting it towards locations removed from the actual insult, like the lymph nodes. On the flip side, excessive retardation or complete inhibition of antigen presentation by N-chlorinated plasma proteins could contribute to chronic infection and inflammation.Ingested inorganic nitrate (NO3⁻) has multiple effects in the human body including vasodilation, inhibition of platelet aggregation, and improved skeletal muscle function. The functional effects of oral NO3⁻ involve the in vivo reduction of NO3⁻ to nitrite (NO2⁻) and thence to nitric oxide (NO). However, the potential involvement of S-nitrosothiol (RSNO) formation is unclear. We hypothesised that the RSNO concentration ([RSNO]) in red blood cells (RBCs) and plasma is increased by NO3⁻-rich beetroot juice ingestion. In healthy human volunteers, we tested the effect of dietary supplementation with NO3⁻-rich beetroot juice (BR) or NO3⁻-depleted beetroot juice (placebo; PL) on [RSNO], [NO3⁻] and [NO2⁻] in RBCs, whole blood and plasma, as measured by ozone-based chemiluminescence. The median basal [RSNO] in plasma samples (n = 22) was 10 (5-13) nM (interquartile range in brackets). In comparison, the median values for basal [RSNO] in the corresponding RBC preparations (n = 19) and whole blood samples (n = 19) were higher (p less then 0.001) than in plasma, being 40 (30-60) nM and 35 (25-80) nM, respectively. The median RBC [RSNO] in a separate cohort of healthy subjects (n = 5) was increased to 110 (93-125) nM after ingesting BR (12.8 mmol NO3⁻) compared to a corresponding baseline value of 25 (21-31) nM (Mann-Whitney test, p less then 0.01). The median plasma [RSNO] in another cohort of healthy subjects (n = 14) was increased almost ten-fold to 104 (58-151) nM after BR supplementation (7 × 6.4 mmol of NO3⁻ over two days, p less then 0.01) compared to PL. In conclusion, RBC and plasma [RSNO] are increased by BR ingestion. In addition to NO2⁻, RSNO may be involved in dietary NO3⁻ metabolism/actions.Romania is on the first place in Europe with an annual production of honey of 30.9 thousand tons in 2018, while the European Union is on the second place in the world with a total of 283 thousand tons. The most part of the honey production from Romania is exported. The aim of this study was to estimate internal radiation doses and lifetime cancer risk from honey ingestion sampled from several locations on the Romanian territory. The activity concentration of 137Cs and 238U is found to be below the detection limit of the method. The activity of 226Ra ranged from lower than the minimum detectable value ( less then 1.08 Bq·kg-1) to 7.35 ± 1.73 Bq·kg-1. For 232Th and 40K the average recorded values were 1.51 ± 0.74 and 24.08 ± 4.37 Bq·kg-1, respectively. The annual effective dose due to the intake of 232Th, 226Ra, 40K has been assessed ranging from 0.08 to 0.47 (μSv·y-1), 0.35 to 1.65 (μSv·y-1) and 0.04 to 0.33 (μSv·y-1), respectively. 26Ra gives the largest contribution (56-82%) to the total annual effective dose due to ingestion received by consumption of honey, in the samples where it was identified. In the other samples (where 226Ra was below the detection limit), the largest contribution to annual effective dose is due to 232Th (45-85%). The values obtained from the lifetime cancer risk calculation range in the domain from 2.85·10-7 to 1.78·10-6 for 232Th, 1.33·10-6 to 6.22·10-6 for 226Ra and 1.38·10-7 to 1.25·10-6 for 40K. For 137Cs, only one value was recorded 2.20·10-8. The 232Th, 226Ra, 40K and 137Cs activities measured in the present work were comparable with completion of others activated values of honey samples around Europe.
Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH) is a rare disease often associated with carcinoid tumors. We aimed at evaluating the impact of DIPNECH on characteristics and prognosis of patients who underwent radical treatment of pulmonary carcinoid tumors.
We reviewed all patients operated on for curative-intent resection of carcinoid tumor in our department from 2001 to 2020. Cases exhibiting both pathological and radiological features of DIPNECH, as assessed by respective thoracic expert physicians, were analyzed separately.
172 cases of resected carcinoid tumors were identified, including 25 (14.5 %) harboring pathological criteria of DIPNECH and radiologic features like mosaic attenuation (92.0 %), multiple nodules < 5 mm (76.0 %), and mucoid impactions (32 %). In DIPNECH patients, major pulmonary resections were usually performed (92.0 %) and resected tumors were mostly classified as pT1 (92 %). Mean Ki67 staining was 3.7 ± 5.2 %. The early postoperative period was mostlnagement.
The aim of this study was to determine overall survival and recurrence-free survival after resection of bronchopulmonary carcinoids by means of predominantly minimally invasive surgery and lung-sparing resections. In addition, we aimed to identify prognostic factors for overall survival.
Retrospective review of consecutive patients operated for bronchopulmonary carcinoids between January 2009 and October 2020 identified from a prospectively collected database.
A total of 236 patients representing 240 cases of bronchopulmonary carcinoids were included. Of these, 212 (88.3 %) were typical carcinoids, while 28 (11.7 %) were atypical carcinoids. A Video-Assisted Thoracoscopic Surgery (VATS) approach was used in 75 % of cases. There was no 30-day mortality. The median follow-up was 5.6 years for overall survival and 4.7 years for recurrence-free survival. 5- and 10-year overall survival rates were 89 % and 71 %, while 5- and 10-year recurrence-free survival rates were 84 % and 71 %. Patients with atypical carcinoids had significantly reduced overall survival and recurrence-free survival rates (HR 3.4; 95 % CI 1.5-7.6; p = 0.003 and HR 5.4; 95 % CI 2.6-11.4; p < 0.001). Independent predictors of overall survival included atypical carcinoid (HR 2.7; 95 % CI 1.2-6.0; p = 0.018) and age > 60 years (HR 2.9; 95 % CI 1.2-7.3; p = 0.021).
Surgery for bronchopulmonary carcinoids by means of predominantly VATS and lung-sparing resections provides favorable long-term survival. Atypical carcinoids and age > 60 years are independent predictors of poor overall survival.
60 years are independent predictors of poor overall survival.
This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with resected pathologic N2 (pN2) non-small cell lung cancer (NSCLC) with different locoregional recurrence (LRR) risks.
The primary cohort and validation cohort were retrieved from two independent medical centres. Data for all consecutive patients with completely resected pathologic stage T1-3N2M0 NSCLC were analysed. Patients without PORT in the primary cohort were identified as a training set. Significant prognostic factors for LRR were identified by the Fine-Gray model to develop a prognostic index (PI) in the training set.
The primary cohort consisted of 357 patients who met the eligibility criteria (training set, 287 patients without PORT). The external validation cohort consisted of 1044 patients who met the eligibility criteria (validation set, 711 patients without PORT). Heavy cigarette smoking history, clinical N2 status (cN2), and the number of positive lymph nodes >4 were identified as independent risk factors. The PI was computed as follows PI=0.8*smoking history+0.5*cN2+0.7*the number of involved lymph nodes (reference level was assigned the value 1 and risk level the value 2). In the low-risk group (PI score< = 3), PORT showed a trend towards decreased LRR rates but not significantly improved overall survival (OS). In the high-risk group (PI score>3), PORT significantly reduced the risk of LRR and improved OS.
We constructed and validated a PI to predict individually the effect of PORT in patients with completely resected pN2 NSCLC. Patients with a higher PI score can benefit from PORT in terms of OS.
We constructed and validated a PI to predict individually the effect of PORT in patients with completely resected pN2 NSCLC. Patients with a higher PI score can benefit from PORT in terms of OS.The physical phenomena governing hyperpolarization through optical pumping of conduction electrons continue to be explored in multiple semiconductor systems. One early finding has been the asymmetry between the optically pumped nuclear magnetic resonance (OPNMR) signals when generated by different circular polarizations (i.e., light helicities). Because these resonances are asymmetric, the midpoint between the signals prepared with each of the two circular polarizations is either a positive or negative value, termed an "offset" that is representative of an optical Overhauser enhancement. Both negative offsets (in GaAs) and positive offsets (in CdTe) have been observed. The origins of these offsets in semiconductors are believed to arise from thermalized electrons; however, to the best of our knowledge, no study has systematically tested this hypothesis. To that end, we have adopted two configurations for OPNMR experiments-one in which the Poynting vector of the laser light and magnetic field are parallel, and one in which they are antiparallel, while other experimental conditions are kept the same. We find that the OPNMR signal response to a fixed helicity of light depends on the experimental configuration, and this configuration needs to be accounted for in order to properly describe the OPNMR results. Further, studying the offsets as a function of field strength shows that the optical Overhauser enhancement (the offset) increases in magnitude with field strength. Alofanib molecular weight Finally, by describing all angular momentum and phasing conventions unambiguously, we are able to determine that the absorptively-phased appearance of 113Cd (and 125Te) OPNMR in CdTe is a consequence of the sign of the nuclear gyromagnetic ratios for these isotopes.
Read More: https://www.selleckchem.com/products/alofanib-rpt835.html
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