Search Results (62)

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), threatens global wheat production. Breeding resistant varieties is a key to disease control. In this study, 198 modern wheat varieties were phenotyped with the prevalent Pst races CYR33 and CYR34 at the seedling stage and with mixed Pst races at the adult-plant stage. Seven stable resistance varieties with infection type (IT) ≤ 2 and disease severity (DS) ≤ 20% were found, including five Chinese accessions (Zhengpinmai8, Zhengmai1860, Zhoumai36, Lantian36, and Chuanmai32), one USA accession (GA081628-13E16), and one Pakistani accession (Pa12). The genotyping applied a 55K wheat single-nucleotide polymorphism (SNP) array. A genome-wide association study (GWAS) identified 14 QTL using a significance threshold of p ≤ 0.001, which distributed on chromosomes 1B (4), 1D (2), 2B (4), 6B, 6D, 7B, and 7D (4 for CYR33, 7 for CYR34, 3 for mixed Pst races), explaining 6.04% to 18.32% of the phenotypic variance. Nine of these QTL were potentially novel, as they did not overlap with the previously reported Yr or QTL loci within a ±5.0 Mb interval (consistent with genome-wide LD decay). The haplotypes and resistance effects were evaluated to identify the favorable haplotype for each QTL. Candidate genes within the QTL regions were inferred based on their transcription levels following the stripe rust inoculation. These resistant varieties, QTL haplotypes, and favorable alleles will aid in wheat breeding for stripe rust resistance. Full article

Wheat (Triticum aestivum L.) is the world’s most indispensable staple crop and a vital source of food for human diet. Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), constitutes a severe threat to wheat production and in severe cases, the crop fails completely. Anmai1350 (AM1350) is moderately resistant to leaf rust and powdery mildew, and highly susceptible to sheath blight and fusarium head blight. We found that the length and area of mycelium in AM1350 cells varied at different time points of Pst infection. To investigate the molecular mechanism of AM1350 resistance to Pst, we performed transcriptome sequencing (RNA-seq). In this study, we analyzed the transcriptomic changes of the seedling leaves of AM1350 at different stages of Pst infection at 0 h post-infection (hpi), 6 hpi, 24 hpi, 48 hpi, 72 hpi, and 120 hpi through RNA-seq. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was used to validate RNA-seq data. It was determined that there were differences in the differentially expressed genes (DEGs) of AM1350, and the upregulation and downregulation of the DEGs changed with the time of infection. At different time points, there were varying degrees of enrichment in the response pathways of AM1350, such as the ”MAPK signaling pathway–plant”, the “plant–pathogen interaction” pathway and other pathways. After Pst infected AM1350, the reactive oxygen species (ROS) content gradually increases. The ROS is toxic to Pst, promotes the synthesis of phytoalexins, and inhibits the spread of Pst. As a result, AM1350 shows resistance to Pst race CYR34. The main objective of this study is to provide a better understanding for resistance mechanisms of wheat in response to Pst infections and to avoid production loss. Full article

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers characterized by the excessive production of blood cells in the bone marrow. These disorders arise from acquired genetic driver mutations, with or without underlying genetic predispositions, resulting in the uncontrolled production of red blood cells, white blood cells, or platelets. The excessive cell production and abnormal signaling from driver mutations cause chronic inflammation and a higher risk of blood clots and vascular complications. The primary goals of MPN treatment are to induce remission, improve quality of life and survival, as well as to reduce the risk of complications such as thrombosis, vascular events, and leukemic transformation. This review provides a comprehensive update on the diagnosis and therapeutic advancements in major MPN subtypes, including chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, and primary myelofibrosis. It examines these complex diseases from a molecular and evolutionary perspective, highlighting key clinical trials’ long-term follow-up and therapies targeting driver mutations that have transformed treatment strategies. Additionally, several important advancements in addressing challenges such as anemia in myelofibrosis, along with promising emerging therapies, are also discussed. Full article

Background/Objectives: Oxidative stress plays a pivotal role in skin aging and carcinogenesis. Phytochemicals such as sulforaphane (SF, from broccoli sprouts or seeds) or curcumin (CUR, from turmeric) can be highly protective against this stress. They each induce a suite of cytoprotective and antioxidant enzymes that are coordinately transcribed via the Keap1-Nrf2-ARE pathway in mammals, such as the prototypical cytoprotective enzyme NAD(P)H dehydrogenase 1 (NQO1). Methods: Eighteen healthy human volunteers (9 males, 9 females, aged 18–69. were randomized to receive daily glucoraphanin (GR), which is converted to SF upon ingestion (450 mg; 1 mmol), CUR (1000 mg; 2.7 mmol), or both (450 mg GR + 1000 mg CUR), as oral supplements. After 8 days of a diet low in both compounds, blood and urine were collected for compliance and biomarker measurements. Randomized spots on the buttock’s skin were exposed to 2 x M.E.D. of UVB, and punch biopsies were obtained 1 and 3 days later for biomarker and histological measurement. Erythema was measured with a chromameter daily for 3 consecutive days following UVB. The process was repeated after receiving oral supplements, both with and without UVB exposure. Results: Compared to baseline, each treatment (n = 6 for each) induced NQO1 mRNA levels in skin biopsies: 3.1-fold with GR, 3.3-fold with CUR, and 3.6-fold with the combination of GR and CUR. Across all treatments (n = 18), expression of the pro-inflammatory cytokines IL-1β and TNF-α were reduced, as were IL-6, IL-17, STING, and CYR61, though less robustly. Modulation of these biomarkers persisted, but was less pronounced, in biopsies taken following UV exposure. The presence of SF and its metabolites in the skin post-treatment was confirmed by examining 6 of 12 subjects who ingested GR. Supplement effects on erythema following UV exposure were not significant, and no significant changes were measured in the same biomarkers in blood cells (PBMC), or by counting dyskeratotic keratinocytes. Supplements were well tolerated and compliance was excellent. Conclusions: Oral GR and CUR are well tolerated and have for the first time been shown to result in increased expression of cytoprotective genes and reduced expression of inflammatory cytokine genes in human skin in vivo. This mechanism-based clinical study suggests that an antioxidant, anti-inflammatory, and cytoprotective benefit from these oral supplements is delivered to the skin in humans. Full article

Increasing antifungal resistance and side effects of existing drugs demand alternative approaches for treating Candida (C.) infections. This study aimed to comprehensively evaluate the antifungal efficacy of myricetin (MYR), a natural flavonoid, against both fluconazole (FLC)-resistant and susceptible clinical Candida strains, with a particular focus on its inhibitory effects on C. albicans biofilms. Antifungal susceptibility was evaluated on Candida spp. by the broth microdilution method, and the impact of myricetin on C. albicans biofilms was determined using the Cell Counting Kit-8 (CCK-8) assay. To understand the molecular mechanisms underlying the antibiofilm properties of myricetin, expression analysis of genes in the RAS1/cAMP/EFG1 pathway (ALS3, HWP1, ECE1, UME6, HGC1) and cAMP-dependent protein kinase regulation (RAS1, CYR1, EFG1) involved in the transition from yeast to hyphae was performed. Field emission scanning electron microscopy (FESEM) was used to study the ultrastructural changes and morphological dynamics of Candida biofilms after exposure to MYR and FLC. The in vivo toxicity of myricetin was evaluated by survival analysis using the Galleria mellonella model. Myricetin significantly suppressed key genes related to hyphae development (RAS1, CYR1, EFG1, UME6, and HGC1) and adhesion (ALS3 and HWP1) in both clinical and reference Candida strains at a concentration of 640 µg/mL. FESEM analysis revealed that myricetin inhibited hyphae growth and elongation in C. albicans. This study highlights the promising antibiofilm potential of myricetin through a significant inhibition of biofilm formation and hyphal morphogenesis. Full article

Background: The thymus is the central hub of T-cell differentiation, where epithelial cells guide the process of their maturation. Objective: Our goal was to identify and describe progenitor cells within the human thymus that can differentiate into epithelial cells. Methods: When we plated enriched thymic cells in 3D culture conditions, rare individual cells capable of self-renewal and differentiation formed spheroids. Results: Both neonatal and adult thymuses produced similar numbers of spheroids, suggesting that progenitor potential remains consistent across age groups. Some cells within the spheres express genes typical of mature epithelial cells, while others express genes associated with the immature compartment active during thymic organogenesis. However, there were also cells expressing PDGFRβ. We treated the tissues with 2-deoxyguanosine before digestion, which improved the yield of progenitor cells. We also cultured the enriched stromal thymocytes with Cyr61 and Interleukin-22, which affected the spheroid size. Conclusions: Our efforts towards thymic reconstitution are ongoing, but our research uncovers previously unknown characteristics of the elusive epithelial progenitor population. Full article

We investigated the transcription of circadian clock genes in publicly available datasets of gene expression in medulloblastoma (MB) tissues using the R2 Genomics Analysis and Visualization Platform. Differential expression of the core clock genes among the four consensus subgroups of MB (defined in 2012 as Group 3, Group 4, the SHH group, and the WNT group) included the core clock genes (CLOCK, NPAS2, PER1, PER2, CRY1, CRY2, BMAL1, BMAL2, NR1D1, and TIMELESS) and genes which encode proteins that regulate the transcription of clock genes (CIPC, FBXL21, and USP2). The over-expression of several clock genes, including CIPC, was found in individuals with the isochromosome 17q chromosomal aberration in MB Group 3 and Group 4. The most significant biological pathways associated with clock gene expression were ribosome subunits, phototransduction, GABAergic synapse, WNT signaling pathway, and the Fanconi anemia pathway. Survival analysis of clock genes was examined using the Kaplan–Meier method and the Cox proportional hazards regression model through the R2 Genomics Platform. Two clock genes most significantly related to survival were CRY1 and USP2. The data suggest that several clock proteins, including CRY1 and USP2, be investigated as potential therapeutic targets in MB. Full article

Stripe rust, induced by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive fungal diseases of wheat worldwide. Thinopyrum ponticum, a significant wild relative for wheat improvement, exhibits innate immunity to this disease. To transfer the stripe rust resistance gene from Th. ponticum to wheat, two translocation lines, SN21171 and SN52684, were produced through distant hybridization techniques. Disease evaluation results showed that these two lines were immune to Pst species CYR32 at the adult plant stage. Molecular cytogenetic analyses and specific intron-targeting markers amplification results revealed that SN21171 and SN52684 harbor several T3E^b-3DS·3DL and T1E^b-1BS·1BL translocation chromosomes. Furthermore, the comparison of the chromosome karyotype from two translocation lines and their recurrent parent YN15, revealed that structural variation occurred in chromosomes 2A, 5A, 2B, 4B, 5B, and 6B in SN21171 and chromosomes 5A, 3B, 4B, 5B, 6B, and 7B in SN52684. Agronomic trait assessments uncovered advantageous properties in both lines, with SN21171 matching the recurrent parent and SN52684 exhibiting elevated higher grain number per main spike and increased thousand grain weight. These two translocation lines and specific markers may apply to wheat stripe rust-resistance breeding. Full article

Xinjiang is an important region due to its unique epidemic characteristics of wheat stripe rust disease caused by Puccinia striiformis f. sp. tritici. Some previous studies on race identification were conducted in this region, but it is still unclear how temporal changes affect the dynamics, diversity, and virulence characteristics of Pst races in Xinjiang. To gain a better understanding, we compared the race data from spring and winter wheat crops of 2022 with that of 2021. Our results showed a significant change in virulence frequency in 2022. Vr10, Vr13, and Vr19 exhibited an increasing trend, with a frequency of ≥18%, while the maximum decline was observed in Vr1, Vr3, and Vr9, with a frequency of ≤−25%. It was found that Yr5 and Yr15 remained effective against Xinjiang Pst races. The race diversity increased from 0.92 (70 races out of 345 isolates) to 0.94 (90 races out of 354 isolates) in 2022, with G22G being the dominant race group. Race CYR34 became prevalent in the region in 2022, while the LvG grouped was wiped out in 2022, from both summer and winter crop seasons. HyG and SuG groups showed an overall declining trend. Overall prevalent races showed over-summering and over-wintering behaviors in Xinjiang. The number of new races occurrence frequency increased by 34% in 2022, indicating a potential change in the population structure of Pst. It is crucial to introduce newly resistant gene cultivars in this region and to establish rust-monitoring protocols to prepare for any future epidemics. Full article

Candida species, opportunistic pathogens that cause various infections, pose a significant threat due to their ability to form biofilms that resist antifungal treatments and immune responses. The increasing resistance of Candida spp. and the limited availability of effective treatments have prompted the research of natural compounds as alternative therapies. This study assessed the antifungal properties of RA against Candida species, focusing on its impact on C. albicans biofilms and the underlying mechanisms. The antifungal efficacy of RA was evaluated using the CLSI M27-A3 microdilution method on both fluconazole-susceptible and -resistant strains. Biofilm formation by C. albicans was assessed through a crystal violet assay, while its antibiofilm activity was analyzed using an MTT assay and field emission scanning electron microscopy (FESEM). Gene expression related to biofilm formation was studied using quantitative real-time PCR (qRT-PCR), and statistical analysis was performed with an ANOVA. Among the 28 Candida strains tested, RA exhibited minimum inhibitory concentration (MIC) values ranging from 160 to 1280 μg/mL. At a 640 μg/mL concentration, it significantly reduced the expression of genes associated with adhesion (ALS3, HWP1, and ECE1), hyphal development (UME6 and HGC1), and hyphal cAMP-dependent protein kinase regulators (CYR1, RAS1, and EFG1) in RAS1-cAMP-EFG1 pathway (p < 0.05). FESEM analysis revealed a reduction in hyphal networks and disruptions on the cell surface. Our study is the first to demonstrate the effects of RA on C. albicans adhesion, hyphae development, and biofilm formation through gene expression analysis with findings supported by FESEM. This approach distinguishes our study from previous studies on the effect of RA on Candida. However, the high MIC values of RA limit its antifungal potential. Therefore, more extensive research using innovative methods is required to increase the antifungal effect of RA. Full article

Breast cancer is a major global health concern as it is the primary cause of cancer death for women. Environmental radiation exposure and endogenous factors such as hormones increase breast cancer risk, and its development and spread depend on cell motility and migration. The expression of genes associated with cell motility, such as ADAM12, CYR61, FLRT2, SLIT2, VNN1, MYLK, MAP1B, and TUBA1A, was analyzed in an experimental breast cancer model induced by radiation and estrogen. The results showed that TUBA1A, SLIT2, MAP1B, MYLK, and ADAM12 gene expression increased in the irradiated Alpha3 cell line but not in the control or the malignant Tumor2 cell line. Bioinformatic analysis indicated that FLERT2, SLIT2, VNN1, MAP1B, MYLK, and TUBA1A gene expressions were found to be higher in normal tissue than in tumor tissue of breast cancer patients. However, ADAM12 and CYR61 expressions were found to be higher in tumors than in normal tissues, and they had a negative correlation with ESR1 gene expression. Concerning ESR2 gene expression, there was a negative correlation with CYR61, but there was a positive correlation with FLRT2, MYLK, MAP1B, and VNN1. Finally, a decreased survival rate was observed in patients exhibiting high expression levels of TUBA1A and MAP1B. These genes also showed a negative ER status, an important parameter for endocrine therapy. The genes related to motility were affected by ionizing radiation, confirming its role in the initiation process of breast carcinogenesis. In conclusion, the relationship between the patient’s expression of hormone receptors and genes associated with cell motility presents a novel prospect for exploring therapeutic strategies. Full article

Cyanobacteria are cosmopolitan organisms; nonetheless, climate change and eutrophication are increasing the occurrence of cyanobacteria blooms (cyanoblooms), thereby raising the risk of cyanotoxins in water sources used for drinking, agriculture, and livestock. This study aimed to determine the presence of cyanobacteria, including toxigenic cyanobacteria and the occurrence of cyanotoxins in the El Pañe reservoir located in the high-Andean region, Arequipa, Peru, to support water quality management. The study included morphological observation of cyanobacteria, molecular determination of cyanobacteria (16S rRNA analysis), and analysis of cyanotoxins encoding genes (mcyA for microcystins, cyrJ for cylindrospermopsins, sxtl for saxitoxins, and AnaC for anatoxins). In parallel, chemical analysis using Liquid Chromatography coupled with Mass Spectrometry (LC-MS/MS) was performed to detect the presence of cyanotoxins (microcystins, cylindrospermopsin, saxitoxin, and anatoxin, among others) and quantification of Microcystin-LR. Morphological data show the presence of Dolichospermum sp., which was confirmed by molecular analysis. Microcystis sp. was also detected through 16S rRNA analysis and the presence of mcyA gene related to microcystin production was found in both cyanobacteria. Furthermore, microcystin-LR and demethylated microcystin-LR were identified by chemical analysis. The highest concentrations of microcystin-LR were 40.60 and 25.18 µg/L, in May and November 2022, respectively. Microcystins were detected in cyanobacteria biomass. In contrast, toxins in water (dissolved) were not detected. Microcystin concentrations exceeded many times the values established in Peruvian regulation and the World Health Organization (WHO) in water intended for human consumption (1 µg/L). This first comprehensive report integrates morphological, molecular, and chemical data and confirms the presence of two toxigenic cyanobacteria and the presence of microcystins in El Pañe reservoir. This work points out the need to implement continuous monitoring of cyanobacteria and cyanotoxins in the reservoir and effective water management measures to protect the human population from exposure to these contaminants. Full article

Cyanobacteria are adaptable and dominant organisms that exist in many harsh and extreme environments due to their great ecological tolerance. They produce various secondary metabolites, including cyanotoxins. While cyanobacteria are well studied in surface waters and some aerial habitats, numerous other habitats and niches remain underexplored. We collected 61 samples of: (i) biofilms from springs, (ii) aerial microbial mats from buildings and subaerial mats from caves, and (iii) water from borehole wells, caves, alkaline, saline, sulphidic, thermal, and iron springs, rivers, seas, and melted cave ice from five countries (Croatia, Georgia, Italy, Serbia, and Slovenia). We used (q)PCR to detect cyanobacteria (phycocyanin intergenic spacer—PC-IGS and cyanobacteria-specific 16S rRNA gene) and cyanotoxin genes (microcystins—mcyE, saxitoxins—sxtA, cylindrospermopsins—cyrJ), as well as amplicon sequencing and morphological observations for taxonomic identification. Cyanobacteria were detected in samples from caves, a saline spring, and an alkaline spring. While mcyE or sxtA genes were not observed in any sample, cyrJ results showed the presence of a potential cylindrospermopsin producer in a biofilm from a sulphidic spring in Slovenia. This study contributes to our understanding of cyanobacteria occurrence in diverse habitats, including rare and extreme ones, and provides relevant methodological considerations for future research in such environments. Full article

Stripe rust (Puccinia striiformis West. f.sp. tritici, Pst) is a destructive disease that seriously threatens wheat production globally. Exploring novel resistance genes for use in wheat breeding is an urgent need, as continuous Pst evolution frequently leads to a breakdown of host resistance. Here, we identified a set of wheat–Dasypyrum villosum 01I139 (V#6) disomic introgression lines for the purpose of determining their responses to a mixture of Pst isolates CYR32, CYR33 and CYR34 at both seedling and adult-plant stages. The results showed that all introgression lines exhibited high susceptibility at the seedling stage, with infection-type (IT) scores in the range of 6–8, whereas, for chromosomes 5V#6 and 7V#6, disomic addition lines NAU5V#6-1 and NAU7V#6-1 displayed high resistance at the adult-plant stage, indicating that adult-plant resistance (APR) genes were located on them. Further, in order to transfer the stripe-rust resistance on chromosome 7V#6, four new wheat–D. villosum introgression lines were identified, by the use of molecular cytogenetic approaches, from the self-pollinated seeds of 7D and 7V#6, in double monosomic line NAU7V#6-2. Among them, NAU7V#6-3 and NAU7V#6-4 were t7V#6L and t7V#6S monosomic addition lines, and NAU7V#6-5 and NAU7V#6-6 were homozygous T7DS·7V#6L and T7DL·7V#6S whole-arm translocation lines. Stripe-rust tests and genetic analyses of chromosome 7V#6 introgression lines revealed a dominant APR gene designated as Yr7VS on the chromosome arm 7V#6S. Comparison with the homozygous T7DL·7V#6S translocation line and the recurrent parent NAU0686 showed no significant differences in yield-related traits. Thus, T7DL·7V#6S whole-arm translocation with the APR gene Yr7VS provided a valuable germplasm for breeding for resistance. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease characterized by unknown causes and a poor prognosis. Recent research indicates that age-related mechanisms, such as cellular senescence, may play a role in the development of this condition. However, the relationship between cellular senescence and clinical outcomes in IPF remains uncertain. Methods: Data from the GSE70867 database were meticulously analyzed in this study. The research employed differential expression analysis, as well as univariate and multivariate Cox regression analysis, to pinpoint senescence-related genes (SRGs) linked to prognosis and construct a prognostic risk model. The model’s clinical relevance and its connection to potential biological processes were systematically assessed in training and testing datasets. Additionally, the expression location of prognosis-related SRGs was identified through immunohistochemical staining, and the correlation between SRGs and immune cell infiltration was deduced using the GSE28221 dataset. Result: The prognostic risk model was constructed based on five SRGs (cellular communication network factor 1, CYR61, stratifin, SFN, megakaryocyte-associated tyrosine kinase, MATK, C-X-C motif chemokine ligand 1, CXCL1, LIM domain, and actin binding 1, LIMA1). Both Kaplan-Meier (KM) curves (p = 0.005) and time-dependent receiver operating characteristic (ROC) analysis affirmed the predictive accuracy of this model in testing datasets, with respective areas under the ROC curve at 1-, 2-, and 3-years being 0.721, 0.802, and 0.739. Furthermore, qRT-RCR analysis and immunohistochemical staining verify the differential expression of SRGs in IPF samples and controls. Moreover, patients in the high-risk group contained higher infiltration levels of neutrophils, eosinophils, and M1 macrophages in BALF, which appeared to be independent indicators of poor prognosis in IPF patients. Conclusion: Our research reveals the effectiveness of the 5 SRGs model in BALF for risk stratification and prognosis prediction in IPF patients, providing new insights into the immune infiltration of IPF progression. Full article