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The objective of this study was to assess changes in proline, Glycine Betaine (GB), photosynthetic pigment concentration, Membrane Stability Index (MSI), and grain yield of wheat cultivars induced by Supplemental Irrigation (SI) in the terminal growth stages. Two field experiments with four irrigation levels (rainfed, SI at booting stage, SI at booting and anthesis stages, SI at booting, anthesis, and grain filling stages) and five cultivars (Rejaw, Sardari, Homa, Azar2, and Sirwan) were conducted during the 2015-2017 growing seasons. Results indicated that, overall, SI increased cultivars' chlorophyll concentration, MSI, and grain yield. Proline and GB highly accumulated under drought stress, but rapidly decreased after SI; the severity of the decrease in proline concentration was more remarkable. Sardari and Azar2 cultivars exhibited greater MSI, proline, and GB accumulation during drought stress and more rapid recovery from drought. Our results suggest that the ability of the wheat cultivars to maintain functions during drought and recover after SI during the terminal growth stage is essential for determining final grain yield. [ABSTRACT FROM AUTHOR]

The aim of this study was to select wheat genotypes most resistant to drought stress. The experiment was conducted at the research farms of the Faculty of Agriculture, Kurdistan University, Sanandaj, Iran, during 2014-2015 and 2015-2016. A randomized complete block design with three replicates using 20 genotypes of rain-fed wheat was applied. Cluster analysis of different wheat genotypes segregated the genotypes into 3 groups. Comparison between the groups in the first crop year revealed that the second and third groups exhibited the highest rate of radiation-use efficiency (RUE), and the first group had the lowest. Grain yield was highest in the third group and lowest in the first group, with an average of 219.87 g/m2 and 173.40 g/m2, respectively. In the second crop year, the highest rate of RUE was reported in the first group and lowest in the second and third groups. The highest grain yield was observed in the second group and the lowest in the third group (315.40 g/m2 and 253.75 g/m2, respectively). Based on the results of the biplot, high-yield genotypes in the first year of cultivation included G14 (263.00 g/m2), G20 (264.50 g/m2), G18 (214.00 g/m2) and G19 (222.50 g/m2). Based on the results obtained by cluster and PCA analysis under stress conditions, we concluded that several traits play a role in determining the grain yield of wheat.

The fundamental aim of this research was to evaluate the effects of Funneliformis mosseae on nutrient uptake and distribution in solo cropping and intercropping of common bean Phaseolus vulgaris and dill Anethum graveolens in the field, using a factorial arrangement of treatments. The factors were seven cropping systems including (a) common bean sole cropping (40 plants m−2), (b) dill sole cropping at different densities (25, 50 and 75 plants m−2) and (c) the additive intercropping of dill/common bean (25/40, 50/40 and 75/40 plants m−2), with (+ AM) or without (− AM) arbuscular mycorrhiza colonisation. In all cropping systems, AM colonisation improved dry weight and P, K, Fe, Zn and Mn contents of dill plants. Cultivable bacterial community was also increased in the dill/common bean intercropping. Yield of essential oil in dill shoot was improved as a result of AM colonisation and intercropping. [ABSTRACT FROM AUTHOR]

Wheat is a staple food consumed by the majority of people in the world and its production needs to be doubled to feed the growing population. On the other hand, global wheat productivity is greatly affected due to drought and low fertility of soil under arid and semi-arid regions. Application of supplementary irrigation and plant growth-promoting rhizobacteria (PGPR) has been suggested as sustainable measures to combat drought stress and to improve soil fertility and, hence, crop yield. This research was undertaken to study the effect of supplementary irrigation together with a combination of various PGPR on the growth and yield of two wheat cultivars, namely Sardari and Sirvan. The results of variance analysis (mean of squares) showed that the effect of irrigation, cultivar, and irrigation and biofertilizer and irrigation on height, spike length, seed/spike, and numbers of spikes/m2, 1000-seed weight, and grain yield were significant at 1% probability level. The effect of cultivar and irrigation interactions showed that the highest grain yield was obtained in a treatment with two additional irrigations in Sirvan cultivar (5015.0 kg/ha) and Sardari (4838.9 kg/ha) as compared to the 3598 kg/ha and 3598.3 kg/h grain yield in Sirvan and Sardari cultivars with similar treatment, but without irrigation, i.e., dryland farming. Drought conditions significantly affected the wheat grain yield while supplementary irrigation resulted in 39.38% and 34.48% higher yields in Sirvan and Sardari cultivars. [ABSTRACT FROM AUTHOR]

The ability of the gut microbiome to adapt to a new environment and utilize a new metabolite or dietary compound by inducing structural variations (SVs) in the genome has an important role in human health. Here, we discuss recent data on host genetic regulation of SV induction and its use as a new therapeutic approach., Competing Interests: Declaration of interests The authors have no potential conflict of interest to be declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Wheat productivity is constrained by genetic, agronomic, and climate factors, though it is an important crop for food production worldwide. The present study evaluated the effect of bio-fertilizer consortia and seaweed extracts on the growth and yield of two wheat varieties under different irrigation regimes in a field study. This experiment was conducted in a split-split plot based on a randomized complete block design with four replications in 2018 and 2019. Irrigation treatments were the main factor, wheat variety (Sardari and Sirvan) the sub-factor, and bio-fertilizers the sub-sub-factors. The results showed that irrigation regimes significantly improved leaf width, number of leaves, fresh weight of roots and shoots, osmotic potential, leaf water content, and number of stomata respectively by 57.53, 38.59, 106.65, 135.29, 87.92, 14.22 and 13.77, 88.02 and 96.11 percent compared to dry-land conditions. Applying one- and two-times irrigation increased grain yield by 51% and 79%, respectively, and the response varied in wheat varieties. Sardari variety due to having smaller leaf dimensions (Leaf length and width) and lower fresh and dry weight of roots and shoots, as well as lower leaf and tissue water content, had lower grain yield than the Sirvan variety. All the bio-fertilizers positively impacted the growth and yield of both varieties. However, the highest average grain yield in the first and second years of the experiment (with an average of 5226.25 and 4923.33 kg/ha, respectively) were found under the combined application of Mycorrhiza + Nitrozist and Phosphozist + Seaweed extract. The results of the present study underscore the importance of irrigation regimes and consortia of bio-fertilizers for improving grain yield. This study also highlighted the resilience of the studied wheat varieties and bio-fertilizers to projected climate changes. These findings could provide insights into adaptive strategies for mitigating the impact of climate change on wheat production., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The application of green microextraction techniques (METs) is constantly being developed in different areas including pharmaceutical, forensic, food and environmental analysis. However, they are less used in biological monitoring of workers in occupational settings. Developing valid extraction methods and analytical techniques for the determination of occupational indicators plays a critical role in the management of workers' exposure to chemicals in workplaces. Microextraction techniques have become increasingly important because they are inexpensive, robust and environmentally friendly. This study aimed to provide a comprehensive review and interpret the applications of METs and novel sorbents and liquids in biological monitoring. Future perspectives and occupational indicators that METs have not yet been developed for are also discussed., (© 2024 John Wiley & Sons Ltd.)

This cross-sectional study was performed to assess whether systemic inflammatory indices, including systemic inflammation response index (SIRI), systemic immune‑inflammation index (SII), and aggregate index of systemic inflammation (AISI), can be considered as possible inflammatory markers in silica-exposed workers with no diagnosis of silicosis. We studied 371 non-silicotic workers exposed to respirable silica dust (RSD) and 1422 reference workers. The workers' exposure to RSD were assessed and the inflammatory indices were compared between subgroups of the exposed workers based on the severity and duration of exposure. Correlations between inflammatory indices and the pulmonary function parameters were investigated. Also, the receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off values of the SII, SIRI, and AISI. Significant dose-response relationships were observed between duration of exposure and all indices except monocytes and LMR. No significant interaction was observed between duration of exposure to RSD and smoking. Borderline significant correlations were observed between AISI and SIRI with forced expiratory volume (FEV1) and FEV1 to forced vital capacity (FVC) ratio. Higher AUCs were obtained for SII and AISI, respectively. The cut-off values for these biomarkers to be considered abnormal were > 348.48 for SII, > 183.78 for AISI, and > 0.768 for SIRI. Overall, the present study showed for the first time, that SII, AISI, and SIRI might be considered as available, easy-to-obtain, and non-expensive markers of inflammation in non-silicotic workers with a long duration of exposure to RSD who are at risk of developing silicosis in subsequent years., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Non-immune cells, like innate immune cells, can develop a memory-like phenotype in response to priming with microbial compounds or certain metabolites, which enables an enhanced response to a secondary unspecific stimulus. This paper describes a step-by-step protocol for the induction and analysis of trained immunity in human endothelial and smooth muscle cells. We then describe steps for cell culture with cryopreserved vascular cells, subcultivation, and induction of trained immunity. We then provide detailed procedures for downstream analysis using ELISA and qPCR. For complete details on the use and execution of this protocol, please refer to Sohrabi et al. (2020) 1 and Shcnack et al. 2 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives. The present study aimed to assess whether occupational exposure to low concentrations of benzene, toluene, ethylbenzene and xylene (BTEX) is associated with color vision impairment. Methods. We queried PubMed, Scopus, Embase, Web of Science and ProQuest as the main databases, as well as gray literature such as Google Scholar. A random-effects model was used to assess relative risk. A funnel plot was created to assess publication bias. Meta-regression analysis was applied to identify variables that explain the between-study variation in the reported risk estimate. Results. An overall standardized mean difference of 0.529 (95% confidence interval [0.269, 0.788]; p  < 0.0001) was obtained in the random-effects model, which corresponded to a medium-size effect. Duration and the levels of exposure to benzene, toluene and xylene were the significant predictors of the magnitude of the combined risk estimate. Chronic exposure to low levels of BTEX was associated with dyschromatopsia determined by the color confusion index. Conclusions . The impairments can occur even at exposures lower than the occupational exposure limits of BTEX. However, there are several flaws in the determination of workers' exposure, which did not allow to establish how low a level of these chemicals can cause color vision impairment.

Understanding the immune response to Leishmania infection and identifying biomarkers that correlate with protection are crucial for developing effective vaccines. One intriguing aspect of Leishmania infection is the persistence of parasites, even after apparent lesion healing. Various host cells, including dendritic cells, fibroblasts, and Langerhans cells, may serve as safe sites for latent infection. Memory T cells, especially tissue-resident memory T cells (T RM ), play a crucial role in concomitant immunity against cutaneous Leishmania infections. These T RM cells are long-lasting and can protect against reinfection in the absence of persistent parasites. CD4 + T RM cells, in particular, have been implicated in protection against Leishmania infections. These cells are characterized by their ability to reside in the skin and rapidly respond to secondary infections by producing cytokines such as IFN-γ, which activates macrophages to kill parasites. The induction of CD4 + T RM cells has shown promise in experimental immunization, leading to protection against Leishmania challenge infections. Identifying biomarkers of protection is a critical step in vaccine development and CD4 + T RM cells hold potential as biomarkers, as their presence and functions may correlate with protection. While recent studies have shown that Leishmania -specific memory CD4 + T-cell subsets are present in individuals with a history of cutaneous leishmaniasis, further studies are needed to characterize CD4 + T RM cell populations. Overall, this review highlights the importance of memory T cells, particularly skin-resident CD4 + T RM cells, as promising targets for developing effective vaccines against leishmaniasis and as biomarkers of immune protection to assess the efficacy of candidate vaccines against human leishmaniasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nateghi-Rostami and Sohrabi.)

Cutaneous leishmaniasis, a parasitic disease caused by Leishmania major, is a widely frequent form in humans. To explore the importance of the host gut microbiota and to investigate its changes during L. major infection, two different groups of mouse models were assessed. The microbiome of two parts of the host gut-ileum and colon-from infected and non-infected mice were characterised by sequencing of 16S rDNA using an Ion Torrent PGM platform. Microbiome analysis was performed to reveal changes related to the susceptibility and the genetics of mice strains in two different gut compartments and to compare the results between infected and non-infected mice. The results showed that Leishmania infection affects mainly the ileum microbiota, whereas the colon bacterial community was more stable. Different biomarkers were determined in the gut microbiota of infected resistant mice and infected susceptible mice using LEfSe analysis. Lactobacillaceae was associated with resistance in the colon microbiota of all resistant mice strains infected with L. major. Genes related to xenobiotic biodegradation and metabolism and amino acid metabolism were primarily enriched in the small intestine microbiome of resistant strains, while genes associated with carbohydrate metabolism and glycan biosynthesis and metabolism were most abundant in the gut microbiome of the infected susceptible mice. These results should improve our understanding of host-parasite interaction and provide important insights into the effect of leishmaniasis on the gut microbiota. Also, this study highlights the role of host genetic variation in shaping the diversity and composition of the gut microbiome. KEY POINTS: • Leishmaniasis may affect mainly the ileum microbiota while colon microbiota was more stable. • Biomarkers related with resistance or susceptibility were determined in the gut microbiota of mice. • Several pathways were predicted to be upregulated in the gut microbiota of resistant or susceptible mice., (© 2024. The Author(s).)

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Leishmaniasis, a disease caused by parasites of Leishmania spp., endangers more than 1 billion people living in endemic countries and has three clinical forms: cutaneous, mucocutaneous, and visceral. Understanding of individual differences in susceptibility to infection and heterogeneity of its pathology is largely lacking. Different mouse strains show a broad and heterogeneous range of disease manifestations such as skin lesions, splenomegaly, hepatomegaly, and increased serum levels of immunoglobulin E and several cytokines. Genome-wide mapping of these strain differences detected more than 30 quantitative trait loci (QTLs) that control the response to Leishmania major . Some control different combinations of disease manifestations, but the nature of this heterogeneity is not yet clear. In this study, we analyzed the L. major response locus Lmr15 originally mapped in the strain CcS-9 which carries 12.5% of the genome of the resistant strain STS on the genetic background of the susceptible strain BALB/c. For this analysis, we used the advanced intercross line K3FV between the strains BALB/c and STS. We confirmed the previously detected loci Lmr15 , Lmr18 , Lmr24 , and Lmr27 and performed genetic dissection of the effects of Lmr15 on chromosome 11. We prepared the interval-specific recombinant strains 6232HS1 and 6229FUD, carrying two STS-derived segments comprising the peak linkage of Lmr15 whose lengths were 6.32 and 17.4 Mbp, respectively, and analyzed their response to L. major infection. These experiments revealed at least two linked but functionally distinct chromosomal regions controlling IFNγ response and IgE response, respectively, in addition to the control of skin lesions. Bioinformatics and expression analysis identified the potential candidate gene Top3a . This finding further clarifies the genetic organization of factors relevant to understanding the differences in the individual risk of disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Krayem, Sohrabi, Havelková, Gusareva, Strnad, Čepičková, Volkova, Kurey, Vojtíšková, Svobodová, Demant and Lipoldová.)

Background: The adverse health effects of silica are still a major concern in some industries. The purpose of this study was to evaluate pulmonary function in a group of sub-radiological silicotic workers after 11 years of silica dust exposure., Methods: The study sample consisted of 381 exposed and 254 non-exposed workers. The history of pulmonary function parameters was obtained from workers' medical records. The data were collected through interviews with employees and completing questionnaires on demographic variables, detailed occupational and medical history, and respiratory symptoms. Workers' exposure to silica dust was also determined., Results: The mean frequency of workers' exposure to silica dust was 6.3 times greater than its exposure limit. All pulmonary function parameters were significantly lower in the silica-exposed workers, and the difference between the two groups was still statistically significant after adjusting the potential confounding variables. FEV1 showed the greatest reduction, and FVC and FEV1 showed a significant decreasing trend. Also the prevalence of respiratory symptoms was significantly higher in smokers than in nonsmokers among silica-exposed workers., Conclusions: Even in the absence of radiographic evidence of silicosis, exposure to high levels of silica dust is associated with reductions in pulmonary function. In the absence of radiological evidence of silicosis, progressive deterioration of FEV1 over time most likely indicates sub-radiological silicosis. The effects were associated with the severity and duration of exposure. Exposure to sub-TLV levels of silica dust may not affect pulmonary function. Smoking appears to have a synergistic effect in relatively high silica exposures., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

To evaluate the effect of useful soil microorganisms and organic compounds on physiological characteristics and yield of two wheat cultivars under supplementary irrigation conditions, a study was conducted in the Agriculture Research Farm of Kurdistan University during the two cropping seasons of 2017-2018 and 2018-2019. A split-split plot-based study on a randomized complete block design with four replicates was used as an experimental design. The main factor was irrigation at three levels, including control without irrigation, supplementary irrigation in the booting stage, and supplementary irrigation in the booting and flowering stages. Two wheat cultivars, namely, Sardari and Sirvan, as sub-factors and application of bio-fertilizers in eight levels, including the use of bio-fertilizers containing: Mycorrhiza, Seaweed extract, Nitrozist and Phosphozist, Mycorrhiza + Nitrozist and Phosphozist, Seaweed extract + Nitrozist and Phosphozist, Mycorrhiza + Seaweed extract, Mycorrhiza + Nitrozist and Phosphozist + Seaweed extract, and non-application of bio-fertilizers, were considered as sub-factors. The results of both seasons of the experiment showed that the application of bio-fertilizers compared to the control treatment at all irrigation levels increased root volume, leaf relative water content (RWC), membrane stability index (MSI), and photosynthetic pigment content. The highest amount of H 2 O 2 , proline, and soluble carbohydrates were obtained in wheat under dry land conditions, and supplementary irrigation, especially two-time irrigation, significantly reduced the values of these traits. Supplementary irrigation also increased grain yield, so that in the conditions of two-time irrigation compared to the non-irrigation treatment (dry land), in the first and second seasons, the grain yield increased by 79.51 and 78.69%, respectively. Application of bio-fertilizers (Mycorrhiza + Nitrozist and Phosphozist + Seaweed extract) in comparison with the non-application of these fertilizers, due to increased root volume, RWC, MSI, and content of photosynthetic pigments, increased the grain yield in the first and second seasons of the experiment by 8.04 and 6.96%, respectively. As a result, suitable microorganisms and seaweed can improve wheat resistance mechanisms to water deficit, which along with using supplementary irrigation that saves water consumption improves plant growth and yield in areas faced with water shortage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Najafi Vafa, Sohrabi, Mirzaghaderi and Heidari.)

Reprogramming of metabolic pathways in monocytes and macrophages can induce a proatherosclerotic inflammatory memory called trained innate immunity. Here, we have analyzed the role of the Liver X receptor (LXR), a crucial regulator of metabolism and inflammation, in oxidized low-density lipoprotein (oxLDL)-induced trained innate immunity. Human monocytes were incubated with LXR agonists, antagonists, and oxLDL for 24 h. After five days of resting time, cells were restimulated with the TLR-2 agonist Pam3cys. OxLDL priming induced the expression of LXRα but not LXRβ . Pharmacologic LXR activation was enhanced, while LXR inhibition prevented the oxLDL-induced inflammatory response. Furthermore, LXR inhibition blocked the metabolic changes necessary for epigenetic reprogramming associated with trained immunity. In fact, enrichment of activating histone marks at the IL-6 and TNFα promotor was reduced following LXR inhibition. Based on the differential expression of the LXR isoforms, we inhibited LXRα and LXRβ genes using siRNA in THP1 cells. As expected, siRNA-mediated knock-down of LXRα blocked the oxLDL-induced inflammatory response, while knock-down of LXRβ had no effect. We demonstrate a specific and novel role of the LXRα isoform in the regulation of oxLDL-induced trained immunity. Our data reveal important aspects of LXR signaling in innate immunity with relevance to atherosclerosis formation.

Nowadays, the use of the growth regulator salicylic acid for improving a plant's resistance to environmental stresses such as drought is increasing. The present study investigated the effect of salicylic acid on the physiological traits, antioxidant enzymes, yield, and quality of Allium hirtifolium (shallots) under drought conditions for three years (2016-2017, 2017-2018, and 2018-2019). The experiment was conducted as a split-plot based on a randomized complete block design with four repeats. Irrigation as the main factor in four levels of 100% (full irrigation), 75% and 50% of the plant water requirements with non-irrigation (dryland), and salicylic acid as the sub-factor in four levels of 0, 0.75, and 1 mmol, were the studied factors in this research. The combined analysis of three-year data showed that drought reduced leaf relative water content (RWC), membrane stability index (MSI), chlorophyll content, onion yield, and increased activity of antioxidant enzymes, proline content, tang, and allicin of shallots. Shallot spraying with salicylic acid improved leaf RWC, MSI, chlorophyll content, and onion yield. The highest yield of onion (1427 gr m -2 ) belonged to full irrigation and foliar application of 1 mmol salicylic acid. The lowest yield (419.8 gr m -2 ) belonged to plats with non-irrigation and non-application of salicylic acid. By improving the effective physiological traits in resistance to water deficit, salicylic acid adjusted the effects of water deficit on the yield of shallots. Foliar application of 1 mmol salicylic acid in dryland and irrigation of 50% of the plant water requirement increased onion yield by 15.12% and 29.39%, respectively, compared to the control treatment without salicylic acid.

Tissue damage caused by an infection oran autoimmune disease triggers degradation of collagen in the extracellular matrix (ECM), which further enhances inflammation. Therefore, improving ECM in aninflamed tissue can be exploited as a potential therapeutic target. A recentstudy emphasised an innovative approach against COVID-19 using polymerised type I collagen (PTIC) that improves disease severity through a hitherto unknownmechanism. In this paper, we provide an overview of potential mechanism thatmay explain the anti-inflammatory effect of collagen peptides. In addition,the paper includes a brief summary of possible side effect of collagendeposition in inflammatory diseases. Altogether, current knowledge suggeststhat collagen may potentially reduce the residual risk in inflammatorydiseases; however, the detailed mechanism remains elusive., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Competing Interests: The authors have declared that no competing interests exist.

Differences in frequencies of blood cell subpopulations were reported to influence the course of infections, atopic and autoimmune diseases, and cancer. We have discovered a unique mouse strain B10.O20 containing extremely high frequency of myeloid-derived cells (MDC) in spleen. B10.O20 carries 3.6% of genes of the strain O20 on the C57BL/10 genetic background. It contains much higher frequency of CD11b + Gr1 + cells in spleen than both its parents. B10.O20 carries O20-derived segments on chromosomes 1, 15, 17, and 18. Their linkage with frequencies of blood cell subpopulations in spleen was tested in F 2 hybrids between B10.O20 and C57BL/10. We found 3 novel loci controlling MDC frequencies: Mydc1, 2 , and 3 on chromosomes 1, 15, and 17, respectively, and a locus controlling relative spleen weight ( Rsw1 ) that co-localizes with Mydc3 and also influences proportion of white and red pulp in spleen. Mydc1 controls numbers of CD11b + Gr1 + cells. Interaction of Mydc2 and Mydc3 regulates frequency of CD11b + Gr1 + cells and neutrophils (Gr1 + Siglec-F - cells from CD11b + cells). Interestingly, Mydc3 / Rsw1 is orthologous with human segment 6q21 that was shown previously to determine counts of white blood cells. Bioinformatics analysis of genomic sequence of the chromosomal segments bearing these loci revealed polymorphisms between O20 and C57BL/10 that change RNA stability and genes' functions, and we examined expression of relevant genes. This identified potential candidate genes Smap1, Vps52, Tnxb , and Rab44. Definition of genetic control of MDC can help to personalize therapy of diseases influenced by these cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Krayem, Sohrabi, Javorková, Volkova, Strnad, Havelková, Vojtíšková, Aidarova, Holáň, Demant and Lipoldová.)

Background: Nurses experience many job tensions, which lead to job burnout. The consequences of nurses' job burnout include absenteeism, reduced quality of patient care, interpersonal conflicts with colleagues, physical and mental problems, reluctance to provide care with patients, and quitting the job., Objective: The present study aimed to investigate the prevalence of job burnout among nurses in Iran using a meta-analysis method., Method: The study was conducted through a meta-analysis method based on the PRISMA checklist. An unlimited search was conducted until 2020 to access the Persian and English papers in national databases, including Medlib, SID, Iranmedex, and Magiran, and databases including Cochrane, Science-Direct, PubMed, Scopus, and Web of Science. The keywords were "job burnout, nurse, and Iran." The data were searched and extracted by two researchers independently. All analyses were performed using version 2.0 of the Comprehensive Meta-Analysis (CMA) software., Results: The prevalence of job burnout was investigated in 14 papers with a sample size of 2271 individuals with an average age of 31.44 years old, and a confidence interval of 55% (44-66%). Fars province, with 89.2%, had the highest, and Zanjan province, with 25.9%, experienced the lowest prevalence of job burnout. The overall prevalence of job burnout was 44% in males and 66% in females so that the highest prevalence was in women., Conclusion: The prevalence of job burnout in nurses was high in some areas of Iran. A special attention by managers is needed in this field because of the several roles played by the nurses in the healthcare system and the improvement of public health. Implementation of plans to reduce the job burnout and to improve the mental health of nurses by reducing work hours, giving more opportunities to them to express their opinion(s) in amount of salary and benefits, and creating better working conditions are recommended.

Recent studies emphasize the importance of low-density lipoprotein cholesterol (LDL-C) in altering the hematopoietic cell compartment of bone marrow and of high-density lipoprotein cholesterol (HDL-C) in inhibiting metabolic endotoxemia-induced inflammation. The data suggest that these lipoproteins may exert their inflammatory or anti-inflammatory roles by modulating innate immune memory. Targeting specific LDL-C and HDL-C subfractions could therefore potentially reduce the residual risk in hepatic and cardiometabolic disease., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Unhealthy lifestyles and dietary habits often lead to diet-associated inflammatory diseases such as obesity and atherosclerosis. Recent studies have provided novel insight into the role of RIPK1 in inflammation and metabolism. RIPK1 silencing can reduce diet-induced obesity, nonalcoholic fatty liver disease (NAFLD), and atherosclerosis by reducing inflammation, lipid synthesis, and inflammasome activation. Targeting RIPK1 may therefore attenuate chronic metabolic disease and would likely be therapeutic., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Age is a key risk factor associated with the severity of symptoms caused by SARS-CoV-2, and there is an urgent need to reduce COVID-19 morbidity and mortality in elderly individuals. We discuss evidence suggesting that trained immunity elicited by BCG vaccination may improve immune responses and can serve as a strategy to combat COVID-19 in this population., Competing Interests: M.G.N. and L.A.B.J. are scientific founders of Trained Therapeutics and Discoveries (TTxD). The other authors declare no competing interests., (© 2021 Elsevier Inc.)

Lallemantia iberica ( L. iberica ) is an important dry season medicinal plant. Drought, an important abiotic stress, adversely affects the plant's metabolism, which can be alleviated by plant growth regulators like brassinolides. A two-year field experiment was conducted in 2017-2018 to determine the effects of three different irrigation regimes and four brassinolide concentrations on the L. iberica biochemical properties. A split-plot based on a completely randomized block design in three replicates was used as an experimental design with the following irrigation regimes: full watering, watering until flowering and watering until branching. These were the main plots, and 0, 0.5, 1 and 1.5 μM brassinolide concentrations were applied as the subplots. The results showed that many antioxidant enzymes and some biochemical parameters were affected by brassinolide treatment. Furthermore, the highest membrane stability and grain yield were produced in full watering treatment in the second year, and these treatments were not affected by brassinolide application. Several concentrations of brassinolide differently affected the studied treatments, and our study suggests that the amelioration of the effects of the drought stress on L. iberica could possibly be achieved through brassinolide-induced elevation of reactive oxygen species (ROS) scavenging defense systems. There is a need for complementary research to prove the effectiveness of foliar application of this growth regulator to improve the growth and yield of L. iberica under water shortage conditions.

Recent data have revealed that fructose-rich diet triggers inflammation and lipid synthesis. Furthermore, lipid metabolism, cholesterol synthesis and sterol regulatory element binding protein-2 (SREBP-2) activation correlates with coronavirus disease 2019 (COVID-19)-induced cytokine storm. High fructose consumption result in SREBPs activation, altered cholesterol and lipid synthesis and may establish an innate immune memory in the cells, leading to severe COVID-19 in patients with obesity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

COVID-19 is a severe health problem in many countries and has altered day-to-day life in the whole world. This infection is caused by the SARS-CoV-2 virus, and depending on age, sex and health status of the patient, it can present with variety of clinical symptoms such as mild infection, a very severe form or even asymptomatic course of the disease. Similarly to other viruses, innate immune response plays a vital role in protection against COVID-19. However, dysregulation of innate immunity could have a significant influence on the severity of the disease. Despite various efforts, there is no effective vaccine against the disease so far. Recent data have demonstrated that the Bacillus Calmette-Guérin (BCG) vaccine could reduce disease severity and the burden of several infectious diseases in addition to targeting its primary focus tuberculosis. There is growing evidence for the concept of beneficial non-specific boosting of immune responses by BCG or other microbial compounds termed trained immunity, which may protect against COVID-19. In this manuscript, we review data on how the development of innate immune memory due to microbial compounds specifically BCG can result in protection against SARS-CoV-2 infection. We also discuss possible mechanisms, challenges and perspectives of using innate immunity as an approach to reduce COVID-19 severity., Competing Interests: MG Netea and LAB Joosten are scientific founders of Trained Therapeutics and Discoveries (TTxD). The other authors declare no conflict of interest., (© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLDL). Here, we have investigated whether the regulatory networks of trained innate immunity also control endothelial cell activation following oxLDL treatment. Human aortic endothelial cells (HAECs) were primed with oxLDL for 24 h. After a resting time of 4 days, cells were restimulated with the TLR2-agonist PAM3cys4. OxLDL priming induced a proinflammatory memory with increased production of inflammatory cytokines such as IL-6, IL-8 and MCP-1 in response to PAM3cys4 restimulation. This memory formation was dependent on TLR2 activation. Furthermore, oxLDL priming of HAECs caused characteristic metabolic and epigenetic reprogramming, including activation of mTOR-HIF1α-signaling with increases in glucose consumption and lactate production, as well as epigenetic modifications in inflammatory gene promoters. Inhibition of mTOR-HIF1α-signaling or histone methyltransferases blocked the observed phenotype. Furthermore, primed HAECs showed epigenetic activation of ICAM-1 and increased ICAM-1 expression in a HIF1α-dependent manner. Accordingly, live cell imaging revealed increased monocyte adhesion and transmigration following oxLDL priming. In summary, we demonstrate that oxLDL-mediated endothelial cell activation represents an immunologic event, which triggers metabolic and epigenetic reprogramming. Molecular mechanisms regulating trained innate immunity in innate immune cells also regulate this sustained proinflammatory phenotype in HAECs with enhanced atheroprone cell functions. Further research is necessary to elucidate the detailed metabolic regulation and the functional relevance for atherosclerosis formation in vivo., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Diabetes mellitus is an important cardiovascular risk factor characterized by elevated plasma glucose levels. High glucose (HG) negatively influences endothelial cell (EC) function, which is characterized by the inability of ECs to respond to vascular endothelial growth factor (VEGF-A) stimulation. We aimed to identify potential strategies to improve EC function in diabetes., Methods and Results: Human umbilical cord endothelial cells (HUVECs) were subjected to hyperglycemic milieu by exposing cells to HG together with glucose metabolite, methylglyoxal (MG) in vitro. Hyperglycemic cells showed reduced chemotactic responses towards VEGF-A as revealed by Boyden chamber migration assays, indicating the development of "VEGF resistance" phenotype. Furthermore, HG/MG-exposed cells were defective in their general migratory and proliferative responses and were in a pro-apoptotic state. Mechanistically, the exposure to HG/MG resulted in reactive oxygen species (ROS) accumulation which is secondary to the impairment of thioredoxin (Trx) activity in these cells. Pharmacological and genetic targeting of Trx recapitulated VEGF resistance. Functional supplementation of Trx using thioredoxin mimetic peptides (TMP) reversed the HG/MG-induced ROS generation, improved the migration, proliferation, survival and restored VEGF-A-induced chemotaxis and sprouting angiogenesis of hyperglycemic ECs. Importantly, TMP treatment reduced ROS accumulation and improved VEGF-A responses of placental arterial endothelial cells isolated from gestational diabetes mellitus patients., Conclusions: Our findings suggest a putative role for Trx in modulating EC function and its functional impairment in HG conditions contribute to EC dysfunction. Supplementation of TMP could be used as a novel strategy to improve endothelial cell function in diabetes., Competing Interests: Declaration of competing interest None declared., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: The concept of trained innate immunity describes a long-term proinflammatory memory in innate immune cells. Trained innate immunity is regulated through reprogramming of cellular metabolic pathways including cholesterol and fatty acid synthesis. Here, we have analyzed the role of Liver X Receptor (LXR), a key regulator of cholesterol and fatty acid homeostasis, in trained innate immunity., Methods and Results: Human monocytes were isolated and incubated with different stimuli for 24 h, including LXR agonists, antagonists and Bacillus Calmette-Guerin (BCG) vaccine. After 5 days resting time, cells were restimulated with the TLR2-agonist Pam3cys. LXR activation did not only increase BCG trained immunity, but also induced a long-term inflammatory activation by itself. This inflammatory activation by LXR agonists was accompanied by characteristic features of trained innate immunity, such as activating histone marks on inflammatory gene promoters and metabolic reprogramming with increased lactate production and decreased oxygen consumption rate. Mechanistically, LXR priming increased cellular acetyl-CoA levels and was dependent on the activation of the mevalonate pathway and IL-1β signaling. In contrast to mevalonate pathway inhibition, blocking fatty acid synthesis further increased proinflammatory priming by LXR., Conclusion: We demonstrate that LXR activation induces a proinflammatory trained immunity phenotype in human monocytes through epigenetic and metabolic reprogramming. Our data reveal important novel aspects of LXR signaling in innate immunity., (Copyright © 2020 Sohrabi, Sonntag, Braun, Lagache, Liebmann, Klotz, Godfrey, Kahles, Waltenberger and Findeisen.)

Leishmaniasis is a serious health problem in many countries, and continues expanding to new geographic areas including Europe and USA. This disease, caused by parasites of Leishmania spp. and transmitted by phlebotomine sand flies, causes up to 1.3 million new cases each year and despite efforts toward its functional dissection and treatment it causes 20-50 thousands deaths annually. Dependence of susceptibility to leishmaniasis on sex and host's genes was observed in humans and in mouse models. Several laboratories defined in mice a number of Lmr ( Leishmania major response ) genetic loci that control functional and pathological components of the response to and outcome of L. major infection. However, the development of its most aggressive form, visceral leishmaniasis, which is lethal if untreated, is not yet understood. Visceral leishmaniasis is caused by infection and inflammation of internal organs. Therefore, we analyzed the genetics of parasite load, spread to internal organs, and ensuing visceral pathology. Using a new PCR-based method of quantification of parasites in tissues we describe a network-like set of interacting genetic loci that control parasite load in different organs. Quantification of Leishmania parasites in lymph nodes, spleen and liver from infected F 2 hybrids between BALB/c and recombinant congenic strains CcS-9 and CcS-16 allowed us to map two novel parasite load controlling Leishmania major response loci, Lmr24 and Lmr27 . We also detected parasite-controlling role of the previously described loci Lmr4, Lmr11, Lmr13, Lmr14, Lmr15 , and Lmr25 , and describe 8 genetic interactions between them. Lmr14, Lmr15, Lmr25 , and Lmr27 controlled parasite load in liver and lymph nodes. In addition, Leishmania burden in lymph nodes but not liver was influenced by Lmr4 and Lmr24 . In spleen, parasite load was controlled by Lmr11 and Lmr13 . We detected a strong effect of sex on some of these genes. We also mapped additional genes controlling splenomegaly and hepatomegaly. This resulted in a systematized insight into genetic control of spread and load of Leishmania parasites and visceral pathology in the mammalian organism.

Many pathogens, ranging from viruses to multicellular parasites, promote expansion of MDSCs, which are myeloid cells that exhibit immunosuppressive features. The roles of MDSCs in infection depend on the class and virulence mechanisms of the pathogen, the stage of the disease, and the pathology associated with the infection. This work compiles evidence supported by functional assays on the roles of different subsets of MDSCs in acute and chronic infections, including pathogen-associated malignancies, and discusses strategies to modulate MDSC dynamics to benefit the host.

Myeloid cells play a pivotal role in regulating innate and adaptive immune responses. In inflammation, autoimmunity, and after transplantation, myeloid cells have contrasting roles: on the one hand they initiate the immune response, promoting activation and expansion of effector T-cells, and on the other, they counter-regulate inflammation, maintain tissue homeostasis, and promote tolerance. The latter activities are mediated by several myeloid cells including polymorphonuclear neutrophils, macrophages, myeloid-derived suppressor cells, and dendritic cells. Since these cells have been associated with immune suppression and tolerance, they will be further referred to as myeloid regulatory cells (MRCs). In recent years, MRCs have emerged as a therapeutic target or have been regarded as a potential cellular therapeutic product for tolerance induction. However, several open questions must be addressed to enable the therapeutic application of MRCs including: how do they function at the site of inflammation, how to best target these cells to modulate their activities, and how to isolate or to generate pure populations for adoptive cell therapies. In this review, we will give an overview of the current knowledge on MRCs in inflammation, autoimmunity, and transplantation. We will discuss current strategies to target MRCs and to exploit their tolerogenic potential as a cell-based therapy.

Objective: Damage and pathogen associated molecular patterns such as oxidized low-density lipoprotein (oxLDL) or bacillus Calmette-Guerin (BCG) vaccine can induce long term pro-inflammatory priming in monocytes and macrophages due to metabolic and epigenetic reprogramming-an emerging new concept called trained innate immunity. Vascular smooth muscle cells express pattern recognition receptors involved in trained innate immunity in monocytes. Here we investigated whether the mechanisms of trained innate immunity also control a proinflammatory phenotype in human coronary smooth muscle cells. Methods: Human coronary smooth muscle cells were primed with oxLDL or BCG for 24 h. After a resting time of 4 to 7 days, the cells were restimulated with either PAM3cys4, LPS or TNFα and cytokine production or mRNA expression were measured. Then, mechanisms of monocyte trained innate immunity were analyzed in smooth muscle cells, including receptors, intracellular pathways as well as metabolic and epigenetic reprogramming. Results: Priming with oxLDL or BCG lead to a significantly increased production of IL6, IL8 and MCP-1 following restimulation. OxLDL priming had little effect on the expression of macrophage or SMC marker genes. Proinflammatory priming of smooth muscle cells induced mTOR-HIF1α-signaling and could be blocked by mTOR-, TLR2-, and TLR4-inhibition. Finally, metabolic and epigenetic mechanisms of trained innate immunity in monocytes could be replicated in smooth muscle cells, including increased glucose consumption, lactate production, responsiveness to 6-fluoromevalonate and mevalonate treatment and inhibition of priming by the histone methyltransferase inhibitor methylthioadenosine (MTA). Conclusion: We demonstrate for the first time that mechanisms of the so called trained innate immunity control a proinflammatory phenotype in non-immune cells of the vascular wall. Our findings warrant further research into the specificity of trained innate immunity as an immune cell response as well as the mechanisms of vascular smooth muscle cells inflammation.

Introduction: Cells of the innate immune system particularly monocytes and macrophages have been recognized as pivotal players both during the initial insult as well as the chronic phase of atherosclerosis. It has recently been shown that oxidized low-density lipoprotein (oxLDL) induces a long-term pro-inflammatory response in monocytes due to epigenetic and metabolic reprogramming, an emerging new concept called trained innate immunity. Changes in the cellular redox state are crucial events in the regulation of many physiologic functions in macrophages including transcription, differentiation and inflammatory response. Here we have analyzed the role of reactive oxygen species (ROS) in regulating this proinflammatory monocyte priming in response to oxLDL-treatment. Methods and Results: Human monocytes were isolated and incubated with oxLDL for 24 h. After 5 days of resting, oxLDL treated cells produced significantly more inflammatory cytokines upon restimulation with the TLR2-agonist Pam3cys. Furthermore, oxLDL incubation induced persistent mTOR activation, ROS formation, HIF1α accumulation and HIF1α target gene expression, while pharmacologic mTOR inhibition or siRNA mediated inhibition of the mTORC1 subunit Raptor prevented ROS formation and proinflammatory priming. mTOR dependent ROS formation was associated with increased expression of NAPDH oxidases and necessary for the emergence of the primed phenotype as antioxidant treatment blocked oxLDL priming. Inhibition of cytosolic ROS formation could also block mTOR activation and HIF1α accumulation suggesting a positive feedback loop between mTOR and cytosolic ROS. Although mitochondrial ROS scavenging did not block HIF1α-accumulation at an early time point (24 h), it was persistently reduced on day 6. Therefore, mitochondrial ROS formation appears to occur initially downstream of the mTOR-cytoROS-HIF1α feedback loop but seems to be a crucial factor that controls the long-term activation of the mTOR-HIF1α-axis. Conclusion: In summary, our data demonstrate that mTOR dependent ROS production controls the oxLDL-induced trained innate immunity phenotype in human monocyte derived macrophages. Pharmacologic modulation of these pathways might provide a potential approach to modulate inflammation, associated with aberrant monocyte activation, during atherosclerosis development.

Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Cytotoxicity and genotoxicity of sodium acetate (SA), sodium diacetate (SDA), and potassium sorbate (PS) was tested on Human Umbilical Vein Endothelial Cells (HUVEC). Cytotoxicity was investigated by MTT assay and flow cytometry analysis, while genotoxicity was evaluated using DNA fragmentation and DAPI staining assays. The growth of treated HUVECs with various concentrations of SA, SDA and PS decreased in a dose-and time-dependent manner. The IC50 of 487.71, 485.82 and 659.96 µM after 24 h and IC50 of 232.05, 190.19 and 123.95 µM after 48 h of treatment were attained for SA, SDA and PS, respectively. Flow cytometry analysis showed that early and late apoptosis percentage in treated cells was not considerable. Also neither considerable DNA fragmentation nor DNA smear was observed using DAPI staining and DNA ladder assays. Overall, it can be concluded that the aforementioned food additives can be used as safe additives at low concentration in food industry., (Copyright © 2018 Elsevier Ltd. All rights reserved.)