Search

The operational lifespan of all four units at the Hungarian Paks Nuclear Power Plant (NPP) has been extended by 20 years beyond the original 30-year term. This extension has been implemented gradually, in one- to two-year increments, since 2013. The Hungarian Atomic Energy Authority, responsible for granting approval for these life extensions, has prescribed the continuous and rigorous monitoring of the reactor pressure vessel (RPV) throughout the plant’s extended service life. Among the key requirements is the validation of the neutron transport calculations, with specific attention to the large Lead Factor (LF), which reaches around 12 at the reactor core’s center. To meet these regulatory requirements, neutron transport calculations and reactor dosimetry measurements using neutron activation detectors (neutron monitors) have been conducted both inside and outside the RPV. Inside measurements were taken in the RPV surveillance channel, while outside measurements were conducted in the cavity adjacent to the outer wall of the RPV. These efforts aim to determine the key parameters of the neutron irradiation and validation is achieved if the experimental results agree with the neutron transport calculations at both the surveillance position and the RPV's outer wall (in the cavity), ensuring that the calculations are also valid for the inner wall of the RPV. This paper presents the validation of experimental data used to confirm the accuracy of the neutron transport calculations. The results of irradiations conducted over one- and four-year periods are compared and analyzed to demonstrate the authenticity of the experimental data for validation of the calculation results.

As estimated having an increased incidence of about 50% until 2040, the diabetic condition could be augmented primarily from astaxanthin contained in carotenoids. This research examines and compares the influence of WSSP and AST complement on Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) level and Total Antioxidant Capacity (TAC) induced high-fat diet streptozotocin (HFD-STZ) in T2DM rats. WSSP 0.89gr/200gr/d (X1) and 1.77gr/200gr/d (X2) groups; and AST supplement 0.09mg/200gr/d (X3) groups were compared with both of positive (K1) and negative (K2) groups. The treatments were administered orally for 21 days to 25 Wistar rats which each group consisted of 5 rats. HOMA-IR and TAC levels were measured by ELISA and ABTs method respectively. TAC levels significantly increased in treatment groups than K1 group (p = 0.008). The increase in the TAC level of the X2 group was greater than the X1 group (p = 0.017). HOMA IR levels were significantly lower in treatment groups than K1 group (p = 0.009). X2 group had a greater decrease in HOMA IR levels compared to X1 (p = 0.016). In consequence, the research findings show a utilitarian effect of WSSP in increasing TAC and decreasing the HOMA-IR index.

An atherogenic diet induces oxidative stress leading to hypercholesterolemia. This condition causes atherosclerosis followed by increased LDL and MDA. Sorghum tempeh contains fiber and antioxidants that can protectively improve LDL and MDA levels. Therefore, this research aims to determine the effect of sorghum tempeh on LDL and MDA levels in atherogenic diet-induced rats compared to sorghum flour. It used a randomized pre-post test with a control group design. The test subjects were 30 male Sprague Dawley rats, consisting of 6 normal conditioned rats (C1), and 24 that were induced by an atherogenic diet (C2, T1, T2, T3) for 2 weeks. Sorghum flour was administered at a dose of 4.095 g (T1) and the sorghum tempeh at 3.041 g (T2) and 6.081 g (T3) for 4 weeks. Furthermore, C2 was constantly induced through an atherogenic diet. Total cholesterol and LDL levels were then analyzed using the CHOD-PAP method, and MDA levels, using the ELISA method. Meanwhile, statistical analysis for these variables was carried out using IBM SPSS Statistics 21 software. The results showed that the administration of sorghum flour and tempeh significantly reduced total cholesterol, LDL, MDA levels in each group (p = 0.001). Furthermore, it showed that there was a significantly strong correlation between LDL and MDA levels before and after treatment (r = 0.610, r = 0.805, and p = 0.001). The administration of sorghum tempeh at a dose of 6.081 g caused the greatest reduction (∆) in LDL levels at -44.19 ±2.58 mg.dL-1, although, it was not the same as normal control. Meanwhile, sorghum flour at a dose of 4.095 g was the most influential in reducing MDA levels to the same as normal control with delta (∆) at -7.67 ±0.37 ng.mL-1. In conclusion, sorghum tempeh and flour were the most effective at reducing LDL and MDA levels, respectively.

Non-alcoholic fatty liver disease (NAFLD) patients have alteration in hemostasis components. Thus, including excess expression of plasminogen activator inhibitor-1 (PAI-1), causing fibrinolysis disorders; the majority of these patients are hypercoagulable state prone to thrombosis. Some evidence suggests that garlic and garlic supplements have antithrombotic and anti-inflammatory properties. Besides, garlic stimulates fibrinolytic activity and normalizes plasma lipid imbalances. Black garlic is processed garlic that is produced through natural aging at a controlled temperature (70 °C) and high humidity (90%) for several days, without other additives. This study aimed to prove the effect of single clove black garlic (SCBG) (Allium sativum Linn) on PAI-1 levels and lipid profiles of NAFLD rats induced by a high-fat fructose diet (HFFD) containing 1.25% cholesterol and 0.5% cholic acid.The rats were then divided into healthy control group (K1+); NAFLD control group without treatment (K2+); 0.9 mg simvastatin treatment group (K1-); 45 mg metformin treatment group (K2-); SCBG 450 mg per 200g BW (X1); 900 mg per 200 g BW (X2); and 1350 mg per 200 g BW (X3). All treatments were administered for 4 weeks via oral gavage. As a result, significant differences in PAI-1 levels and lipid profiles between groups after the administration (p = 0.001) were noted and also by simvastatin and metformin, respectively. There was a correlation between PAI-1 and lipid profile of SCBG treatment. In conclusion, the administration of SCBG (1350 mg per 200 g BB per day) for 4 weeks had a significant effect on PAI-1 levels, and the lipid profiles in Sprague Dawley rats modeled NAFLD (p = 0.001). SCBG has provided benefits that can be useful in the management of NAFLD but it’s not equivalent to medicine.

Type 2 diabetes mellitus (T2DM) may be developed by a cardiovascular complication. T2DM and its complications associated with a decrease in levels of 25 hydroxyvitamin D below normal. The level of 25-OH-D can increase and it can be gained by probiotics supplementation. Dadih is a probiotic useful as antidiabetic, antiatherosclerotic, and it can reduce serum cholesterol. Vitamin D is beneficial for T2DM since it improves insulin production, acts as an anti-inflammatory and prevents dyslipidemia thereby preventing cardiovascular disease. This research aims to investigate the effects of giving dadih-fortified-vitamin-D3 toward caecum-cholesterol-concentration and hs-CRP-levels to T2DM-induced-rats. This study used a randomized pre-post test with control group design in 30 Wistar rats divided into 5 groups, namely T1, T2, and T3-treatment-groups. T3-group was given dadih-fortified-vitamin-D3, while T1 and T2-groups were given vitamin-D3 and dadih, respectively. The control groups were healthy-control (C1), and T2DM (C2). The intervention was given through oral sonde for 28days. The variables analyzed were caecal-cholesterol-concentrations using a spectrophotometer and hs-CRP using the ELISA method. The statistical tests were used for the caecum-cholesterol-concentration and hs-CRP levels. The mean of caecum-cholesterol-concentration in the T3-group (83.68 ±1.93mg.100g-1), was higher than T1 (77.99 ±1.70; p = 0.004) and C2-control (24.39 ±1.47; p = 0.0001). The mean of hs-CRP-level post-intervention in the T3-group (4.21 ±0.41 ng.mL-1), was lower than C2 (17.15 ±0.85;p = 0.0001), T1 (6.59 ±0.27; p = 0.0001) and T2 (5.43 ±0.39; p = 0.004). There is a very strong inverse correlation between the concentration of cholesterol and hs-CRP ( r = -0.979, p = 0.0001). The conclusion is dadih-fortified-vitamin-D3 –intervention is better than its single intervention as an anti-inflammation which might relate to the increased caecum-cholesterol-concentration.

Following an initial Round Robin inter-comparison of gamma spectrometry measurements reported in 2014, this paper presents results from the first part of a second Round Robin inter-comparison commissioned by the European Working Group on Reactor Dosimetry in 2018. Measurements were performed by thirteen European organisations on a set of irradiated neutron activation detectors representative of those commonly used by the Reactor Dosimetry community to measure neutron fluence using gamma spectrometry methods. The radionuclides measured were 110mAg, 58Co, 60Co, 54Mn, and 46Sc. The purpose of the exercise was to demonstrate the level of consistency between participating organisations in blind tests of measurements. The samples used were disks of iron, nickel, titanium, and two standard alloys of aluminium, one of 1% cobalt and the other 1% silver. They were irradiated in the MARIA reactor operated by National Centre for Nuclear Research, Poland. Participants provided their results to an independent referee who collated and compared the data. The results are presented in an anonymised form together with discussion and conclusions which may be drawn from the exercise. Good agreement was obtained with standard deviations for individual measurements between 2.0% (54Mn) and 5.6% (60Co). Overall, the results obtained from the latter Round Robin show less consistency than those from the first Round Robin, which is attributed to the participation of a wider pool of organisations.

Abstract Massive pro-inflammatory cytokines production has been correlated with the pathogenesis of severe dengue disease. The active compound of mangosteen fruit pericarps, α-mangostin, has been commonly used as traditional medicine and dietary supplement. We examined the effect of α-mangostin against dengue virus (DENV) infection in human peripheral blood mononuclear cells (PBMC) by the measurement of virus titer and TNF-α and IFN-γ cytokines concentration post infection. Increasing concentration of α-mangostin inhibited virus replication and reduced inflammatory cytokines expression at 24- and 48-h post infection. Our results support the potential use of α-mangostin as anti-antiviral and anti-inflammatory therapies in the treatment of dengue. Graphic Abstract

T2DM has increase in global-morbidity and mortality. Oxidative stress and adiponectin-levels are important for insulin-resistance and pancreatic-b-cell-dysfunction in T2DM. Okra fruit is rich of quercetin and phytosterol which have positive-effect for T2DM. Research aimed was to study the effect of okra-flour to adiponectin-levels and total-antioxidant-capacity (TAC) in T2DM. Thirty Wistar-rats were divided randomly in five groups. K1 and (X1, X2 and X3)-treated-groups were in T2DM-condition-induced by high-fat-diet-(HFD)-Streptozotochin-(STZ)-nicotinamid-(NA). Healthy-controls-(K2)-group was also used. Okra-flour was given orally for 28 days at doses of 0.1; 0.2 and 0.3 g/Kg-body-weight/d to X1, X2 and X3-groups, respectively. Statistical program was used to analyse the different between pre-post-intervention, and between groups. Correlations between variables were also analysed. The serum-adiponectin and TAC-levels were measured by ELISA and ABTS-methods, respectively. By comparing pre and post-intervention, adiponectin levels of all-intervention-(X1, X2, X3)-group were increase (p = 0.027 for X1 and X2; p = 0.028 for X3), while in the same period the decrease were found in group K1 (p = 0.026) and K2 (p = 0.028). Increase-TAC-levels pre-post-intervention was observed in group all-intervention-groups (p = 0.027), while no change in K1 (p = 0.66) and the decrease in group K2 (p = 0.039). Reduce-fasting-blood-glucose-levels pre-post-intervention were shown in the all-intervention-groups (p = 0.028), while for the K1 groups was increase (p = 0.028). There were significant differences between the five-groups on fasting-blood-glucose-levels, adiponectin and TAC-levels, and X3-group showed the highest adiponectin and TAC-levels. Very-strong-correlations were found between glucose-adiponectin-TAC-levels-post-intervention. Okra-flour make better glucose-adiponectin and TAC-levels in T2DM-conditions. Okra dose of 0.30 g/Kg-body-weight/day is the best in increasing adiponectin and TAC-levels.

Background : Sago worm flour (Rhyinchophorus ferrugineus)is a coconut beetle larvae that is processed into flour.This flour contains antioxidants as well as arginine, both of which play a role in modulating oxidative stress including NO involved in immunopathology of cerebral malaria.Objectives : To prove the immunomodulator role of sago worm flour in decreasing circulation NO level at mice who received standard antimalarial therapy Dihydroartemisinin Piperaquine (DHP)Methods : This study was randomized control group post test only design by using 23 Swiss mice which divided into 5 group consist of : K(-) normal mice; K(+) inoculated woth Plasmodium berghei ANKA (PbA); X1 received DHP; X2 received sago worm flour; X3 received both of sago worm flour and DHP. All treatment groups X1,X2 and X3 were inoculated by PbA before treatmen were given. Serum circulation NO level was assessed by ELISA. statistical analysis used was One Way ANOVA followed by Bonferroni post hoc test. Results : The mean NO level in K(-), K(+), X1, X2, and X3 were 1.008 μmol/mL, K(+) 1.338 μmol/mL; while at treatment X1 1.143 μmol/mL, X2 1.410 μmol/mL, dan X3 0.886 μmol/mL. One way ANOVA showed that they were significantly different (p=0.001). Bonferroni post hoc test of X2 was proportional to K(+) (p=1.000), whole had NO level lower than either K(+)(p=0.009) or X2 (p=0.002). Conclusion : The immunomodulatory effects of sago worm flour (Rhyinchophorus ferrugineus) reduced circulating NO levels in standard antimalarial therapy recipients.

Background: High fat diets are known to cause a positive fat balance and consequently to the accumulation of adipose mass, this diet does not seem to stimulate fat oxidation in the same way in obese and lean subjects. HFD was an inducing factor for ICAM-1 expression in the aorta of Wistar rats. HFD effect on ICAM-1 seems to be time dependent. ICAM-1 is one of the first events in the formation of atherosclerotic lesions. HFD up-regulated Cav-1, regulated expression other biomarker in HFD is eNOS. Recent studies showed that E. longifolia Jack protected HFD animal model from atherosclerosis based on the reduce atherosclerotic plaque size and formation HFD-rats treated with E. longifolia Jack. Objective: To prove that Eurycoma longifolia has anti inflammatory effect on endothelial cell blood vessels of Sprague Dawley rat with high fat diet. Method: Study design was experimental study, by used Randomized Post Test only Control Group Design with Kruskal-Wallis test was used to analyze the differences among groups and followed by a Mann Whitney test. Treatment is ethanolic or water extract of Eurycoma longifolia Jack, and out come are sICAM-1 and eNOS levels. Thirty Sprague Dawley (SD) Rat, were divided into 6 groups. C(-) was SD group, C(+) was group with HFD, X1 (SD treated with EL dosage 10 mg/kg), X2 (SD treated with EL dosage 15 mg/kg), X3 (HFD treated with EL dosage 10 mg/kg), X4 (HFD treated with EL dosage 15 mg/kg).

Background: The metabolic syndrome often begins with insulin resistance characterized by hyperinsulinemia and hyperglycemia. Synbiotic yoghurt tanduk banana contains probiotic and prebiotic FOS can improve insulin resistance in metabolic syndrome. Objective: To prove the effect of synbiotic yoghurt tanduk banana can reduce blood glucose levels and insulin levels in metabolic syndrome rats. Method: True-experimental study with randomized controlled group pre-post test design in male wistar rats. Eighteen samples were induced to become metabolic syndrome with high fat fructose diet for 2 weeks and they were divided into 3 groups: control (K) was given standard diet, treatment group 1 (P1), and treatment group 2 (P2) were given sinbiotic yoghurt tanduk banana dose of 0.009 ml/g body weight (BW)/day and 0.018 ml/g BW/day for 2 weeks. Results: The paired t-test showed there were differences of blood glucose levels and insulin levels before and after treatment in P2 group. The Kruskal Wallis test showed there were differences of mean blood glucose levels inter group after treatment (p

Background: The metabolic syndrome, which is characterized by hyperglycemia, obesity, dyslipidemia, hypertension, prothrombic and proinflamatory state, is a risk factor for cardiovascular disease and diabetes mellitus. The synbiotic yogurt of tanduk banana (Musa paradisiaca fa. corniculata) flour contains lactic acid bacteria, fructooligosaccarides, flavonoids, and vitamin C which all of them play role in improving the lipid profile. Objective: The aim of this study was to prove the effect of synbiotic yogurt of tanduk banana flour on lipid profile of metabolic syndrome rats. Method: This study was an true experimental with pre-post test control group design. The subject of this study were 18 metabolic syndrome male Wistar rats divided into 3 groups,i.e control group (standart diet), intervention group I (standart diet and synbiotic yogurt of banana flour 0,009 ml/g weight/day), and intervention group II (standart diet and synbiotic yogurt of banana flour 0,018 ml/g weight/day). The intervention period was 2 weeks. Different test before and after intervention used paired t-test. The difference test between groups used One-Way ANOVA and Kruskal wallis. Results: The result showed that both of intervention group improved lipid profile significantly (p

Background: High fat diet is a diet containing large amounts of fat consistently, the increase dietary fat and cholesterol which have a key role in growing health problems. Extra virgin olive oil associated with prevention of LDL oxidation, beneficial changes in lipid ratios and low risk for CHD. Objective: to determine the anti-inflammatory effect of extra virgin olive oil extract to levels of COX-2 and LOX-1 in the blood in rats induced by high fat diet Methods: This research is an experimental study that used randomized posttest only control group design. 30 Wistar rats which were divided into five groups: group of control (-) which received normal diet and group of control (+) which received high fat diet without EVOO treatment and three high fat diet groups treated by EVOO 1 mL/kg/day, 2 mL/kg/day and 3 mL/kg/day orally for 2 months. The blood was collected from eyes rats and serum separation by centrifuge. COX-2, LOX-1 concentration was measured by the enzyme linked immunosorbent assay (ELISA). Results: The result of this study showed higher COX-2 concentrations in groups treated with EVOO than control group. COX-2 serum levels of negative control where significantly lower than those of rats treated with 2 ml/kg/day (p = 0.047) and 3 ml/kg/day EVOO (p = 0.014). The COX-2 serum levels of group received 1 ml/kg/day were significantly lower than those of rats received 3 ml/kg/day EVOO (p = 0.027). And showed not significantly deferent among all groups (p = 0.570). CONCLUSIONS: The conclusion of this study has showed that extra virgin olive oil extract might have minor anti inflammatory and antioxidant effect in rats.

This article investigates the effect of processing parameters (conditioning temperature and binder content), on final quality of produced agro-pellets for heat energy generation, obtained from four different olive cultivars using different technological parameters. Technological, physical and chemical properties of pellets (carbon, hydrogen, nitrogen and sulphur content, particle density, abrasion length, moisture, ash content, higher and lower heating values, fixed carbon and volatile matter content) have been determined to assess their quality. The performance of Artificial Neural Network (ANN) was compared with the performance of second order polynomial (SOP) model, as well as with the obtained experimental data in order to develop rapid and accurate mathematical model for prediction of final quality parameters of agro-pellets. SOP model showed high coefficients of determination (r2), between 0.692 and 0.955, while ANN model showed high prediction accuracy with r2 between 0.544 and 0.994. [Projekat Ministarstva nauke Republike Srbije, br. III 46005 i br. TR-31055]

Quercetin content in Moringa oleifera has scientific potential antioxidant and anti-inflammation effects by inhibiting the activity of NF-ĸB. In addition, triterpenoids stimulate pancreatic β cell regeneration and increases insulin secretion. This study aimed to discover the effect of Moringa oleifera extract on insulitis and insulin expression in pancreas of Sprague-Dawley male rats. The study was performed at the laboratory of Food and Nutrition Unit of The Inter University Center of Gadjah Mada University and the laboratory of Histology and Cell Biology Faculty of Medicine Gadjah Mada University during May–July 2013. This was a randomized post test only controlled group study. Twenty four rats were included. Blood glucose test was performed on the third day after streptozotocin induction to ensure that all rats were in hyperglycemic condition. The rats were then divided into three groups: one control group and two treatment groups receiving Moringa oleifera ethanolic leaves extract for 21 days in doses of 250 and 500 mg/kg/day, respectively. Histopathological analysis of pancreas were performed by evaluating insulitis based on the infiltration of mononuclear inflammatory cells to the Langerhans islets. Insulin expression was evaluated using Allred score. Statistical analysis used was Kruskal-Wallis test, followed by Mann-Whitney with a level of significance of p

Excessive use of fossil fuels has an extremely negative impact on the environment and climate because it results in toxic gas emission into the atmosphere. The negative effects of the fossil fuels use leads to distinctive need for renewable energy sources that affect environmental pollution less. One of little-used renewable energy source today is biomass. Biomass combustion chambers have been so perfected that we can say that the combustion of biomass (as far as work and serving) equals the combustion of coal or even liquid fuels. The study was conducted in Croatian tobacco factory on the tobacco dryer combustion chambers at 'A' and 'B', with the aim of justified introduction of new chambers as new technological measures. In addition to increasing the income, measures taken to lower drying costs are as important. Such measures are of great importance for the development of certain regions, employment and Republic of Croatia entrepreneurship promotion.

Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs) may play an etiological role in this condition.In a cohort of 73 Indonesian children with dengue hemorrhagic fever (DHF), of which 30 with dengue shock syndrome (DSS), we measured plasma levels of the WPB constituents von Willebrand factor antigen (VWF:Ag), VWF propeptide and osteoprotegerin (OPG), together with activity levels of the VWF-cleaving enzyme ADAMTS-13 and the amount of VWF in a platelet binding conformation (VWF activation factor). Compared with healthy controls (n = 17), children with DHF/DSS had significantly higher levels of VWF:Ag, VWF propeptide and OPG and decreased ADAMTS-13 activity. The VWF activation factor was also significantly higher in DHF/DSS and highest in children who died. There were significant differences in the kinetics of the various WPB constituents: VWF propeptide and OPG levels decreased toward discharge, while VWF:Ag levels were lower than expected at enrollment with plasma levels increasing toward discharge. Moreover, VWF propeptide levels correlated better with markers of disease severity (platelet count, liver enzymes, serum albumin and pleural effusion index) than corresponding VWF levels. Together, these findings suggest that there is consumption of VWF in DHF/DSS. In 4 out of 15 selected children with low ADAMTS-13 levels on admission, we found a remarkable reduction in the large and intermediate VWF multimers in the discharge blood samples, consistent with an acquired von Willebrand disease.These findings suggest that severe dengue is associated with exocytosis of WPBs with increased circulating levels of VWF:Ag, VWF propeptide and OPG. High circulating levels of VWF in its active conformation, together with low ADAMTS-13 activity levels, are likely to contribute to the thrombocytopenia and complications of dengue. During the convalescence phase, qualitative defects in VWF with loss of larger VWF multimers may develop.

Replacing fossil fuels with renewable, bio-based alternatives is inevitable for the modern chemical industry, in line with the 12 principles of green chemistry. 2,5-Furandicarboxylic acid (FDCA) is a promising platform molecule that can be derived from 5-hydroxymethyl furfural (HMF) via sustainable electrochemical oxidation. Herein, we demonstrate TEMPO-mediated electrooxidation of HMF to FDCA in ElectraSyn 2.0 using inexpensive commercially available electrodes: graphite anode and stainless-steel cathode, thereby avoiding the often cumbersome electrode preparation. Key parameters such as concentration of HMF, KOH, and catalyst loading were optimized by experimental design. Under the optimized conditions, using only a low amount of TEMPO (5 mol %), high yield and Faradaic efficiency of 96 % were achieved within 2.5 h. Moreover, since FDCA is a monomer of the bio-based poly(ethylene furanoate), PEF, we aimed to investigate its recovery by depolymerization, which could be of paramount importance in the circular economy of the FDCA. For this, a new polar aprotic solvent, methyl sesamol (MeSesamol), was used, allowing the facile depolymerization of PEF at room temperature with high monomer yields (up to 85 %), while the cosolvent MeSesamol was recycled with high efficiency (95-100 %) over five reaction cycles., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

This study sought to compare the behavior of Treg subsets displaying different coexpression patterns of Neuropilin-1 (Nrp1) and Helios, under the influence of gut stress unrelated to hematopoietic stem cell transplantation, pretransplantation conditioning, and posttransplant gastrointestinal acute graft versus host disease (GI-aGvHD). Host CD4 + /CD25 hi /Foxp3 + Treg cells, identified by flow cytometry, were isolated from various tissues of mice affected by these stressors. Expression of CD25, CTLA-4, CD39, OX40, integrin-β7, LAG3, TGFβ/LAP, granzyme-A, -B, and interleukin-10 was compared in four Treg subsets displaying Helios or Nrp1 only, both or none. Fluorescence-activated cell sorter-sorted Treg subsets, displaying markers affected in a conditioning- and GI-aGVHD-restricted manner, were further investigated by transcriptome profiling and T-cell suppression assays. We found that conditioning by irradiation greatly diminished the relative frequency of Helios + /Nrp1 + Treg, shifting the balance toward Helios - /Nrp1 - Treg in the host. Upregulation of integrin-β7 and OX40 occurred in GI-aGvHD-dependent manner in Helios + /Nrp1 + cells but not in Helios - /Nrp1 - Treg. Sorted Treg subsets, confirmed to overexpress Nrp1, Helios, OX40, or integrin-β7, displayed superior immunosuppressive activity and enrichment in activation-related messenger RNA transcripts. Our data suggest that conditioning-induced shrinkage of the Nrp1 + /Helios + Treg subset may contribute to the development of GI-GvHD by impairing gut homing and decreasing the efficiency of Treg-mediated immunosuppression., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

Extracellular vesicles (EVs), through their cargo, are important mediators of bystander responses in the irradiated bone marrow (BM). MiRNAs carried by EVs can potentially alter cellular pathways in EV-recipient cells by regulating their protein content. Using the CBA/Ca mouse model, we characterised the miRNA content of BM-derived EVs from mice irradiated with 0.1 Gy or 3 Gy using an nCounter analysis system. We also analysed proteomic changes in BM cells either directly irradiated or treated with EVs derived from the BM of irradiated mice. Our aim was to identify key cellular processes in the EV-acceptor cells regulated by miRNAs. The irradiation of BM cells with 0.1 Gy led to protein alterations involved in oxidative stress and immune and inflammatory processes. Oxidative stress-related pathways were also present in BM cells treated with EVs isolated from 0.1 Gy-irradiated mice, indicating the propagation of oxidative stress in a bystander manner. The irradiation of BM cells with 3 Gy led to protein pathway alterations involved in the DNA damage response, metabolism, cell death and immune and inflammatory processes. The majority of these pathways were also altered in BM cells treated with EVs from mice irradiated with 3 Gy. Certain pathways (cell cycle, acute and chronic myeloid leukaemia) regulated by miRNAs differentially expressed in EVs isolated from mice irradiated with 3 Gy overlapped with protein pathway alterations in BM cells treated with 3 Gy EVs. Six miRNAs were involved in these common pathways interacting with 11 proteins, suggesting the involvement of miRNAs in the EV-mediated bystander processes. In conclusion, we characterised proteomic changes in directly irradiated and EV-treated BM cells, identified processes transmitted in a bystander manner and suggested miRNA and protein candidates potentially involved in the regulation of these bystander processes.

The therapeutic approach to brain metastases has changed significantly in the last 30 years. The development of surgical technique, the use of new MRI techniques, preoperative surgical planning and the administration of intraoperative navigation reduced the risks of surgery and improved the results. In the case of aggressive renal cell carcinomas, we detect brain metastases relatively often, which are difficult to treat, but the improved surgical and radiosurgery techniques can also be used with success. In our report, we present the neurosurgical management of metastatic spreading of renal cell carcinoma to the brain. Modern surgical planning and more precise, tailored approach with modern radiosurgery techniques are able to improve the outcome and prolong survival even in aggressive types of renal cell carcinomas that give rise to brain metastases. In more severe cases and even in the case of multiple brain metastases, cranial surgery can be recommended.

Early detection is critical for minimizing mortality from cancer. Plasma cell-free DNA (cfDNA) contains the signatures of tumor DNA, allowing us to quantify the signature and diagnose early-stage tumors. Here, we report a novel tumor fragment quantification method, TOF (Tumor Originated Fragment) for the diagnosis of lung cancer by quantifying and analyzing both the plasma cfDNA methylation patterns and fragmentomic signatures. TOF utilizes the amount of ctDNA predicted from the methylation density information of each cfDNA read mapped on 6243 lung-tumor-specific CpG markers. The 6243 tumor-specific markers were derived from lung tumor tissues by comparing them with corresponding normal tissues and healthy blood from public methylation data. TOF also utilizes two cfDNA fragmentomic signatures: 1) the short fragment ratio, and 2) the 5' end-motif profile. We used 298 plasma samples to analyze cfDNA signatures using enzymatic methyl-sequencing data from 201 lung cancer patients and 97 healthy controls. The TOF score showed 0.98 of the area under the curve in correctly classifying lung cancer from normal samples. The TOF score resolution was high enough to clearly differentiate even the early-stage non-small cell lung cancer patients from the healthy controls. The same was true for small cell lung cancer patients., Competing Interests: Declaration of competing interest Jong Bhak is the CEO and a major shareholder of Clinomics Inc., Korea. Other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Stroke-induced immunosuppression (SIIS) increases the risk of poststroke infections. We aimed to determine whether failed versus successful thrombolytic therapy (TT) resulted in SIIS-associated changes in peripheral granulocyte markers at 1 week following the insult., Methods: We collected peripheral blood samples from 19 patients with acute ischemic stroke undergoing TT within 6 h after the onset of their first symptoms and 7 days after the insult. Age-matched controls were sampled on one occasion. We compared the expression of CD15 and CD64 on monocytes, granulocytes, and lymphocytes using flow cytometry., Results: The proportion of granulocytes and CD15+ granulocytes was comparable between controls and stroke patients at both time points. While the proportion of CD15bright granulocytes was also comparable, the mean fluorescence intensity (MFI) of CD15 on this subset was reduced in stroke patients by day 7 but was overall higher at both time points compared to controls. The MFI of CD15 on granulocytes was lower in stroke patients with failed TT than in those with successful TT 1 week after the insult., Conclusions: Our current results indicate that TT may not only acutely reduce the systemic inflammatory response following stroke but may also play a role in reversing SIIS at a later stage following the insult, as reflected by the higher expression of the CD15 marker on granulocytes following successful TT., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

We investigated the effect of deep brain stimulation on dynamic balance during gait in Parkinson's disease with motion sensor measurements and predicted their values from disease-related factors. We recruited twenty patients with Parkinson's disease treated with bilateral subthalamic stimulation for at least 12 months and 24 healthy controls. Six monitors with three-dimensional gyroscopes and accelerometers were placed on the chest, the lumbar region, the two wrists, and the shins. Patients performed the instrumented Timed Up and Go test in stimulation OFF, stimulation ON, and right- and left-sided stimulation ON conditions. Gait parameters and dynamic balance parameters such as double support, peak turn velocity, and the trunk's range of motion and velocity in three dimensions were analyzed. Age, disease duration, the time elapsed after implantation, the Hoehn-Yahr stage before and after the operation, the levodopa, and stimulation responsiveness were reported. We individually calculated the distance values of stimulation locations from the subthalamic motor center in three dimensions. Sway values of static balance were collected. We compared the gait parameters in the OFF and stimulation ON states and controls. With cluster analysis and a machine-learning-based multiple regression method, we explored the predictive clinical factors for each dynamic balance parameter (with age as a confounder). The arm movements improved the most among gait parameters due to stimulation and the horizontal and sagittal trunk movements. Double support did not change after switching on the stimulation on the group level and did not differ from control values. Individual changes in double support and horizontal range of trunk motion due to stimulation could be predicted from the most disease-related factors and the severity of the disease; the latter also from the stimulation-related changes in the static balance parameters. Physiotherapy should focus on double support and horizontal trunk movements when treating patients with subthalamic deep brain stimulation., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kelemen, Halász, Muthuraman, Erőss, Barsi, Zádori, Laczó, Kis, Klivényi, Fekete, Bognár, Bereczki and Tamás.)