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Maize dwarf mosaic virus (MDMV) can significantly reduce the growth and development of susceptible varieties of sweet corn. The virus utilises the energy and reserve sources of plant cells to ensure its reproduction in the microspaces formed by cell membranes. Therefore, the severity of stress can be monitored by examining certain physiological changes, for example, changes in the degree of membrane damage caused by lipid peroxidation, as well as changes in the amount of photosynthetic pigments. The activation of antioxidant enzymes (e.g. ascorbate peroxidase, guaiacol peroxidase, glutathione reductase) and the accumulation of phenolic compounds with antioxidant properties can indirectly protect against the oxidative stress caused by the presence of the positive orientation, single-stranded RNA-virus. This study demonstrates the changes in these physiological processes in a sweet corn hybrid (Zea mays cv. saccharata var. Honey Koern.) susceptible to MDMV infection, and suggests that exogenous small RNA treatment can mitigate the damage caused by virus infection., Competing Interests: Declarations. Conflict of interest: No conflict of interest exists in the submission of this manuscript. The authors declare that the work described has not been published previously, and is not under consideration for publication elsewhere, in whole or in part. Consent for publication: The manuscript has been approved for publication by all authors. All the authors listed have approved the manuscript enclosed herewith., (© 2024. The Author(s).)

Maize dwarf mosaic virus (MDMV) is one of the most serious viruses of sweet corn. Utilising the process of RNA interference, the exogenous introduction of small RNA molecules mimicking virus-derived small interfering RNA (siRNA) into the plant prior to infection triggers the antiviral RNA silencing effect, thereby promoting more effective antiviral protection. Hence, a treatment with MDMV-derived small RNA was applied to sweet corn plants one day before MDMV virus inoculation. ALEXA FLUOR®488 fluorophore-bound exogenous siRNA was successfully detected inside intact sweet corn cells using confocal fluorescence microscopy. Furthermore, it was demonstrated that the exogenous siRNA treatment led to a notable upregulation of the AGO1 , AGO2b , AGO10b , AGO18a , DCL1 , DCL3a , DCL4 , RDR1 , and MOP1 genes within 24 h of the treatment. Overall, exogenous siRNA treatment resulted in better virus control of infected sweet corn plants, as indicated by the lower viral RNA and coat protein levels compared to the infected group without pre-treatment., Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01500-2., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. There is no conflict of interest to disclose., (© The Author(s) 2024.)

The physiological condition of plants is significantly affected by viral infections. Viral proliferation occurs at the expense of the energy and protein stores in infected plant cells. At the same time, plants invest much of their remaining resources in the fight against infection, making them even less capable of normal growth processes. Thus, the slowdown in the development and growth processes of plants leads to a large-scale decrease in plant biomass and yields, which may be a perceptible problem even at the level of the national economy. One form of protection against viral infections is treatment with small interfering RNA (siRNA) molecules, which can directly reduce the amount of virus that multiplies in plant cells by enhancing the process of highly conserved RNA interference in plants. The present work demonstrated how pre-treatment with siRNA may provide protection against MDMV (Maize dwarf mosaic virus) infection in sweet corn ( Zea mays cv. saccharata var. Honey Koern). In addition to monitoring the physiological condition of the maize plants, the accumulation of the virus in young leaves was examined, parallel, with changes in the plant RNA interference system and the ethylene (ET) biosynthetic pathway. The siRNA pre-treatment activated the plant antiviral defence system, thus significantly reducing viral RNA and coat protein levels in the youngest leaves of the plants. The lower initial amount of virus meant a weaker stress load, which allowed the plants to devote more energy to their growth and development. In contrast, small RNA pre-treatment did not initially have a significant effect on the ET biosynthetic pathway, but later a significant decrease was observed both in the level of transcription of genes responsible for ET production and, in the amount of ACC (1-aminocyclopropane-1-carboxylic acid) metabolite. The significantly better physiological condition, enhanced RNAi response and lower quantity of virus particles in siRNA pretreated plants, suggested that siRNA pre-treatment stimulated the antiviral defence mechanisms in MDMV infected plants. In addition, the consistently lower ACC content of the plants pre-treated with siRNA suggest that ET does not significantly contribute to the successful defence in this maize hybrid type against MDMV., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for malignant hematopoietic diseases. Cytokines including transforming growth factor β1 (TGFβ1) play a pivotal role in immune reconstruction, and the development of graft versus host disease (GvHD) or infections. The aim of this study was to investigate the role of TGFB1 gene -1347C>T variant in the outcome of HSCT in a cohort of 409 adult recipient-donor pairs. TGFB1 variant was analysed from genomic DNA with LightCycler hybridisation probe method. In case of myeloablative conditioning, donor TGFB1 genotype correlated with overall survival (60-month OS for CC: 62.1 ± 4.8%; CT: 46.8 ± 4.8%; TT: 35.6 ± 9.3%; p = 0.032), which was independent of age, donor type and GvHD prophylaxis in multivariate analysis (HR:2.35, 95%CI:1.35-4.10, p = 0.003). The cumulative incidence of acute GvHD grade III-IV [CC:10%; CT:17%; TT:24%], and non-relapse mortality was higher in TT-carriers (24-month NRM: CC:24%; CT:26%; TT:46%, p = 0.035). We did not find any association between recipient TGFB1 -1347C>T polymorphism and HSCT outcome. Our results suggest that donor TGFB1 -1347C>T may exert an adverse influence on the outcome of myeloablative conditioning transplantation.

Sleep-disordered breathing, a prevalent condition among adult renal transplant (RTx) recipients, has become an established independent risk factor of MetS, and furthermore, it might contribute to increased CV risk. Despite the proven correlations in adults, there is a lack of evidence for its significance in the pediatric RTx population. In this study, we aimed at assessing the prevalence and the clinical correlates of SDB in RTx children. Data of 13 patients (age [mean ± SD]: 14.2 ± 2.7 years) were analyzed. SDB was evaluated by PSG, as severity score OAHI was applied. Carbohydrate metabolism was characterized by OGTT, whereas CV status was studied by ABPM. Three composite end-points were calculated as sum of z-scores: daytime systolic and diastolic BP; nighttime systolic and diastolic BP; and glucose and insulin levels at 120 minutes. Eight patients (61.5%) were diagnosed with SDB of whom five patients (38.5%) had moderate or severe SDB. In linear regression analysis, OAHI during REM was associated with the CV variables (daytime BP P = 0.032, ß = 0.748; nighttime BP P = 0.041, ß = 0.715), and the correlations remained significant after adjustments for BMI. However, we did not confirm a significant association with the metabolic variables. The prevalence of SDB was high, and its severity during REM was a predictor of the BP suggesting that RTx children with SDB might be at risk of developing CV complications, especially HTN similarly to adults., (© 2019 Wiley Periodicals, Inc.)

Background: Recognition of HLA-C2 group alleles on recipient cells by activating killer immunoglobulin like receptors, KIR2DS1 on donor natural killer cells may lead to increased graft-versus-leukemia effect or immunomodulation in patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) influencing disease free and overall survival (OS)., Objective: In the present study, 314 consecutive, allo-HSCT recipient and donor pairs were included with retrospective donor KIR-genotyping and clinical parameters analyzes., Results: After a median follow-up of 23.6 months, recipients with HLA-C2 group allele (rC2) showed improved (p = 0.046) OS if transplanted with KIR2DS1 positive donors (d2DS1) compared to those without one or both of this genetic attribute. Within the myeloablative conditioning (MAC) subgroup (n = 227), rC2 homozygous+d2DS1 patients (n = 14) showed a 5 years OS of 93% followed by rC2 heterozygous+d2DS1 patients (n = 48, 65%) compared to rC2 and/or d2DS1 negatives (47%, p = 0.018). Multivariate analyses indicated rC2+d2DS1 positivity as an independent predictor of OS (HR:0.47, 0.26-0.86, p = 0.014) besides donor type, presence of CMV-reactivation or chemoresistant disease. Among MAC-treated patients, the combined rC2+d2DS1 presence was associated with a markedly decreased cumulative incidence of transplant related mortality (p = 0.0045)., Conclusion: The combination of rC2+d2DS1 may be a favorable genetic constellation in allo-HSCT with MAC potentially reducing transplant related mortality., Competing Interests: The authors have declared that no competing interests exist.

Background: Due to paucity of evidence to guide management of allogeneic haematopoietic stem cell transplantation (allo-HSCT) patients with respiratory syncytial virus (RSV) infections national and international guidelines make disparate recommendations., Methods: The outcomes of allo-HSCT recipients with RSV infection between 2015 and 2017 were assessed using the following treatment stratification; upper respiratory tract infections (URTI) being actively monitored and lower respiratory tract infections (LRTI) treated with short courses of oral ribavirin combined with intravenous immunoglobulin (IVIG, 2 g/kg)., Results: During the study period 49 RSV episodes were diagnosed (47% URTI and 53% LRTI). All patients with URTI recovered without pharmacological intervention. Progression from URTI to LRTI occurred in 15%. Treatment with oral ribavirin given until significant symptomatic improvement (median 7 days [3-12]) and IVIG for LRTI was generally well tolerated. RSV-attributable mortality was low (2%)., Conclusions: In this cohort study, we demonstrate that active monitoring of allo-HSCT patients with RSV in the absence of LRTI was only associated with progression to LRTI in 15% of our patients and therefore appears to be a safe approach. Short course oral ribavirin in combination with IVIG was effective and well-tolerated for LRTI making it a practical alternative to aerosolised ribavirin. This approach was beneficial in reducing hospitalisation, saving nursing times and by using oral as opposed to nebulised ribavirin., (Copyright © 2019 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Haematopoietic stem cell transplantation was proposed as a treatment strategy just over 60 years ago. Owing to great advances in the field, haematopoietic stem cell transplantation has become an established method for the treatment of many haemato-oncological, immunological and hereditary conditions with the potential of cure. The number of haematopoietic stem cell transplants performed worldwide reached one million by 2012. This review provides an overview of autologous and allogeneic haematopoietic stem cell transplantation including disease indications, the individual steps of the procedure and outcome, and highlights achievements in the treatment of autoimmune diseases. Although autoimmune conditions account for only 1% of indications for autologous haematopoietic stem cell transplant, this is increasingly used to treat high-risk autoimmune diseases. Haematopoietic stem cell transplantation can induce long-term remission by resetting the immune system via eradication of autoreactive immune cells and the generation of a de novo self-tolerant immune system. Data seem most encouraging in multiple sclerosis and systemic sclerosis and it is likely that the number of procedures performed to treat these conditions will rise in the future.

Fibroblast growth factor receptor 1 oncogene partner N-terminal like gene (FOPNL) rs72773978 polymorphism was identified as an adverse prognostic factor in multiple myeloma (MM). We aimed to investigate the associations of rs72773978 with clinical characteristics and treatment outcome in 373 Hungarian MM patients. In our cohort, FOPNL polymorphism showed differential prognostic effect that depended on the treatment applied. Among patients treated with non-proteasome inhibitor (PI)-based therapy, carriership of the minor allele was significantly associated with adverse overall survival (p=.022). In contrast, the adverse effect was overcome by the application of PI-containing treatment (p=.048). Multivariate analyses revealed the independent adverse effect of rs72773978 on survival in the non-PI-treated group (p=.045), but not in PI treatment (OS: p=.093). We confirmed the adverse prognostic effect of rs72773978 associated with non-PI-based treatment regimens. Our results point to the importance of genotypic prognostic information associated with complex clinical background MM.

Introduction: The lack of highly effective drugs in many malignancies has prompted scientific interest in the development of alternative treatment strategies. Cellular immunotherapy involving the adoptive transfer of immune cells that potently recognize and eliminate malignantly transformed cells has become a promising new tool in the anticancer armory. Studies suggest that the unique biological properties of umbilical cord blood (UCB) cells could precipitate enhanced anticancer activity; hence, UCB could be an optimal source for immunotherapy with the potential to provide products with 'off-the-shelf' availability., Areas Covered: In this review, the authors summarize data on the transfer of naturally occurring or genetically modified UCB cells to treat cancer. The focus within is on the phenotypic and functional differences compared to other sources, the alloreactive and anticancer properties, and manufacturing of these products. Therapies utilizing cytokine-induced killer (CIK) cells, natural killer (NK) cells and chimeric antigen receptor (CAR) T-cells, are discussed., Expert Opinion: The cellular immunotherapy field has become a growing, exciting area that has generated much enthusiasm. There is evidence that anticancer immunotherapy with UCB-derived products is feasible and safe; however, considering the limited number of clinical trials using UCB-derived products, further studies are warranted to facilitate translation into clinical practice.

The role of HLA system in allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcome is unarguable. In this study we investigated association of HLA-A,-B and-DRB1 alleles with overall survival (OS) in 186 patients undergoing allo-HSCT for lymphoid malignancies. Analyses confirmed significantly better OS for HLA-DRB1∗04 carriers compared with non-carriers (p = 0.01). Survival benefit was confined to male patients (in multivariate analyses p = 0.034, hazard ratio 0.35, 95% confidence interval 0.13-0.92), whereas in females no difference was noted (p = 0.82). Furthermore, donor gender also affected outcome and transplantation from female HLA-DRB1∗04 carrier donors resulted in superior survival compared with female non-carrier donors (p = 0.01). Combined analyses including recipient/donor gender and HLA-DRB1∗04 showed that survival of male patients varied significantly according to donor gender and HLA-DRB1∗04 carriership (p = 0.04) with best survival among HLA-DRB1∗04 carriers transplanted from female donors. Of relevance to our results, HLA-DRB1∗04 has been documented as risk allele group for lymphoid malignancies, and studies described a male-specific risk. We believe that our findings provide further supporting evidence for sex-specific alterations secondary to HLA-DRB1∗04 or related genes. Further studies are warranted to evaluate whether in contrast to general favour of male donors HLA-DRB1∗04 carrier patients with lymphoid malignancies could benefit from transplantation from female donors., (Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: Proteasome subunit beta type 1 (PSMB1) rs12717 polymorphism, a single nucleotide polymorphism with unknown functional effect, was recently reported to influence response to bortezomib-based therapy in follicular lymphoma., Patients and Methods: We retrospectively analyzed the prognostic impact of this polymorphism in 211 consecutively diagnosed multiple myeloma cases, and performed in vitro experiments to look into its functional consequences., Results: On univariate analysis, patients carrying the variant G allele showed significantly shorter progression-free survival (PFS) with a pattern suggestive of a gene-dose effect (PFS 26.4, 22.3, and 16.4 months in C/C, C/G, and G/G patients, respectively, P = .002). On multivariate analysis, carrying the G/G genotype was a significant independent risk factor for relapse (hazard ratio [HR] 2.29, P < .001) with a similar trend in C/G carriers (HR 1.33, P = .097) when compared with the major allele carrier C/C cohort. Our subsequent in vitro analyses demonstrated significantly reduced protease activity in proteasomes of individuals with G/G genotype compared with that of C/C carriers, despite that PSMB1 expression and proteasome assembly remained unaltered. Bortezomib exhibited a lower inhibitory capacity on the caspase- and trypsin-like activity of proteasomes from G/G individuals., Conclusion: Our results show that carriership of PSMB1 rs12717 minor allele is predictive for suboptimal response with bortezomib treatment, which could be explained by less active proteasomes that are less sensitive to bortezomib, and myeloma cells consequently relying on other escape mechanisms to cope with the abundance of misfolded proteins., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Several genetic polymorphisms have been implicated to affect the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of cytokines in acute graft-versus-host disease (aGvHD) is well established and many of the involved cytokines signal through the Janus kinase (JAK) pathways. In this study, we assessed the association of recipient and donor JAK2 46/1 haplotypes and allo-HSCT outcome in a cohort of 124 acute myeloid leukemia patients. Both, recipient and donor 46/1 haplotypes significantly affected aGvHD grades II-IV development (p = 0.006 and p = 0.031, respectively), furthermore the influence of the haplotypes seemed to be additive. In multivariate analyses the recipient haplotype remained independently related (p = 0.012) to aGvHD, while the donor not (p = 0.08). We observed significantly less relapses among haplotype carriers (p = 0.004), but overall survival did not differ (p = 0.732). Our findings suggest that recipient and donor JAK2 46/1 haplotypes might be involved in the regulation of aGvHD.

Introduction and Aim: The publication summarizes the 2548 stem cell transplantations performed in the period of 1993-2015 in Szent Laszló Hospital, Budapest and provides a detailed discussion of the 425 allogeneic transplantations during 2007-2013., Method: The analysis explains the major steps of the evolution of allogeneic stem cell transplantation and compares the results of the unique Hungarian allogeneic center., Results: The significant shift in the transplantation indications from chronic myeloid leukemia to myelodysplastic syndromes and the rising age of the recipients are in line with world wide tendencies. The latter one is the consequence of the introduction and improvement of the concept of reduced intensity conditioning regimens, originally arising from the idea of Endre Kelemen. The most limiting factor, the donor availability seems to be resolved with the use of a new immunomodulating regimen, the application of posttransplantation cyclophosphamide, which allows the transplantation through HLA barriers with haploidentical family donors with comparable results to the HLA matched volunteer unrelated donors. The above mentioned tendencies result the wider use of allogeneic stem cell transplantation less dependent from recipient age, comorbidities and even donor availability., Conclusions: The publication highlights the need of expanding the stem cell transplantation budget and the involvement of new centers in Hungary in allogeneic of stem cell transplantation. Orv. Hetil., 2017, 158(8), 291-297.

Background: The germline telomerase reverse transcriptase (TERT) rs2736100&#95;C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN)., Methods: LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100&#95;C and Janus kinase 2 (JAK2) rs12343867&#95;C tagging 46/1 haplotype in 584 BCR-ABL1-negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals., Results: TERT rs2736100&#95;C showed an increased allele frequency in BCR-ABL1-negative MPN patients compared with controls (62.7%±2.8% vs. 48.8%±3.5%, P < 0.0001) regardless of molecular background or disease type, but not in CML or AML. Combined TERT and JAK2 hetero- or homozygosity conferred even higher risk for classic MPN. Common complications (thrombosis, myelofibrosis, or leukemia) were not associated with the TERT variant; however, adverse survival was noted in TERT variant carrier polycythemia vera patients. MPN patients with the TERT CC genotype had a higher probability (44.4%) to die from solid tumors compared with TERT AC/AA individuals (5.3%; P = 0.004). TERT rs2736100&#95;C carriers had increased risk of solid tumors independently from cytoreductive treatment [3.08 (1.03-9.26), P = 0.045]., Conclusions: TERT rs2736100&#95;C polymorphism predisposes to the development of BCR-ABL1-negative MPN with the co-occurrence of solid tumors, especially with the usage of cytoreductive treatment., Impact: The high frequency of TERT variant in the classic MPN population highlights the importance of the avoidance of long-term cytoreductive treatment in MPN patients., (©2015 American Association for Cancer Research.)

Nuclear factor kappa B (NFKB) plays an important role in multiple myeloma (MM), and bortezomib affects this pathway. We retrospectively analysed the effect of the NFKB1 -94ins/delATTG polymorphism on the survival of 295 MM patients treated at a single centre. The median progression-free survival (PFS) was 790 (659-921) d in patients with NFKB1 homozygous insertion genotype (I/I, n = 99) and 624 (515-733) d in deletion-carriers (I/D&D/D, n = 196, P = 0·013). In multivariate analysis, I/I carriers showed a favourable PFS compared to I/D&D/D with a hazard ratio of 0·622 (0·457-0·847), P = 0·003, in addition to international staging system (ISS) score, fluorescence in situ hybridization (FISH) risk score, age and bortezomib treatment. I/I patients benefited more from bortezomib treatment [PFS 902 (703-1101) and 580 (343-817), P = 0·008] than I/D&D/D patients [PFS 659 (487-831) and 488 (323-653), P = 0·531]; in addition the beneficial effect of low ISS score was not observed in the I/D&D/D group [PFS 639 (454-824) and 650 (458-842), P = 0·226], while it was clear in I/I patients [PFS 1140 (803-1477) and 580 (408-752), P < 0·001]. We conclude that homozygous carriers of the insertion allele of the NFKB1 -94ins/delATTG polymorphism have a better prognosis and probably benefit more from bortezomib treatment than MM patients carrying the deletion allele., (© 2014 John Wiley & Sons Ltd.)

Introduction: Mutations in Janus kinase 2, calreticulin and thrombopoietin receptor genes have been identified in the genetic background of Philadelphia chromosome negative, "classic" myeloproliferative neoplasms., Aim: The aim of the authors was to identify driver mutations in a large myeloproliferative cohort of 949 patients., Method: A complex array of molecular techniques (qualitative and quantitative allele-specific polymerase chain reactions, fragment analyzes, high resolution melting and Sanger sequencing) was applied., Results: All 354 patients with polycythemia vera carried Janus kinase 2 mutations (V617F 98.6%, exon 12: 1.4%). In essential thrombocythemia (n = 468), the frequency of V617F was 61.3% (n = 287), that of calreticulin 25.2% (n = 118), and that of thrombopoietin receptor mutations 2.1% (n = 10), while 11.3% (n = 53) were triple-negative. Similar distribution was observed in primary myelofibrosis (n = 127): 58.3% (n = 74) V617F, 23.6% (n = 30) calreticulin, 6.3% (n = 8) thrombopoietin receptor mutation positive and 11.8% (n = 15) triple-negative., Conclusions: The recent discovery of calreticulin gene mutations led to definite molecular diagnostics in around 90% of clonal myeloproliferative cases.

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK-cell lymphoma, is an uncommon, aggressive non-Hodgkin's lymphoma with cutaneous, lymph node, and bone marrow involvement at presentation. The disease is characterized by early leukemic phase; however, central nervous system involvement is rarely reported. Herein we describe two cases of CD4+/CD56+ hematodermic neoplasm with meningeal manifestation. Microscopic analysis and flow cytometry of cerebrospinal fluid proved to be diagnostic; however, imaging studies were not informative. These observations call attention to the possibility of central nervous system involvement, which could be more common than expected previously. Authors recommend routine cerebrospinal fluid analysis and prophylactic intrathecal chemotherapy in patients with this highly aggressive disease.